Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacodynamic-guided modified continuous reassessment method-based, dose-finding study of rapamycin in adult patients with solid tumors.

PURPOSE Pharmacodynamic studies are frequently incorporated into phase I trials, but it is uncommon that they guide dose selection. We conducted a dose selection study with daily rapamycin (sirolimus) in patients with solid tumors employing a modified continuous reassessment method (mCRM) using real-time pharmacodynamic data as primary dose-estimation parameter. PATIENTS AND METHODS We adapted the mCRM logit function from its classic toxicity-based input data to a pharmacodynamic-based input. The pharmacodynamic end point was skin phospho-P70 change after 28 days. Pharmacodynamic effect was defined as at least 80% inhibition from baseline. The first two dose levels (2 and 3 mg) were evaluated before implementing the mCRM, and the data used to estimate the next dose level based on statistical modeling. Toxicity-based boundaries limited the escalation steps. Other correlates analyzed were positron emission tomography (PET) and computed tomography, pharmacokinetics, phospho-P70 in peripheral-blood mononuclear cells, and tumor biopsies in patients at the maximum-tolerated dose (MTD). RESULTS Twenty-one patients were enrolled at doses between 2 and 9 mg. Pharmacodynamic effect occurred across dose levels, and toxicity boundaries ultimately drove dose selection. The MTD of daily oral rapamycin was 6 mg. Toxicities in at least 20% were hyperglycemia, hyperlipidemia, elevated transaminases, anemia, leucopenia, neutropenia, and mucositis. Pharmacokinetics were consistent with prior data, and exposure increased with dose. No objective responses occurred, but five previously progressing patients received at least 12 cycles. PET showed generalized stable or decreased glucose uptake unrelated to antitumor effect. CONCLUSION mCRM-based dose escalation using real-time pharmacodynamic assessment was feasible. However, the selected pharmacodynamic end point did not correlate with dose. Toxicity ultimately drove dose selection. Rapamycin is a well-tolerated and active oral anticancer agent.
An unusual cause of stroke in an older patient

The case of an older patient admitted with an acute stroke in the presence of atrial fibrillation is presented. Subsequent transthoracic echocardiography and advanced imaging suggested the diagnosis of a large papillary fibroelastoma on the anterior mitral valve leaflet (AML). The patient underwent surgical resection and made an excellent clinical recovery.
Determinants of Household Food Insecurity in Northern Ghana: An Ordered Probit Approach

Even though food insecurity is experienced in different degrees, and in many forms and periods, most studies have often classified food insecurity as mild/very low, moderate/low and severe. This study extends the study on food insecurity by examining the relative occurrence of each of these wide categories using ordered probit model and analysing data from 4,288 households in northern Ghana. The study shows that for each of these categories, households’ rural dwelling, age, land size and access to credit significantly increase food insecurity whilst maize crop output and marital status decrease food insecurity. This study reveals that food insecurity is a rural and productivity problem and not a poverty issue (or inadequate credit). We therefore recommend that credit in the form of inputs such as fertiliser, improved seed and mechanisation should be promoted rather than increasing access to credit (cash) to increase household members purchasing power.
Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome.

RATIONALE The hypothesis that lung collapse is detrimental during the acute respiratory distress syndrome is still debatable. One of the difficulties is the lack of an efficient maneuver to minimize it. OBJECTIVES To test if a bedside recruitment strategy, capable of reversing hypoxemia and collapse in > 95% of lung units, is clinically applicable in early acute respiratory distress syndrome. METHODS Prospective assessment of a stepwise maximum-recruitment strategy using multislice computed tomography and continuous blood-gas hemodynamic monitoring. MEASUREMENTS AND MAIN RESULTS Twenty-six patients received sequential increments in inspiratory airway pressures, in 5 cm H(2)O steps, until the detection of Pa(O(2)) + Pa(CO(2)) >or= 400 mm Hg. Whenever this primary target was not met, despite inspiratory pressures reaching 60 cm H(2)O, the maneuver was considered incomplete. If there was hemodynamic deterioration or barotrauma, the maneuver was to be interrupted. Late assessment of recruitment efficacy was performed by computed tomography (9 patients) or by online continuous monitoring in the intensive care unit (15 patients) up to 6 h. It was possible to open the lung and to keep the lung open in the majority (24/26) of patients, at the expense of transient hemodynamic effects and hypercapnia but without major clinical consequences. No barotrauma directly associated with the maneuver was detected. There was a strong and inverse relationship between arterial oxygenation and percentage of collapsed lung mass (R = - 0.91; p < 0.0001). CONCLUSIONS It is often possible to reverse hypoxemia and fully recruit the lung in early acute respiratory distress syndrome. Due to transient side effects, the required maneuver still awaits further evaluation before routine clinical application.
Statistics for Investigation of Multimodal MR Imaging Data and an Application to Multiple Sclerosis Patients

Magnetic resonance spectroscopy can image axonal damage specifically based on changes in N‐acetyl aspartate (NAA), a neuronal marker. We have developed statistical methods for multimodal analysis of MR spectroscopic images. These methods, which are extensions of mixed‐effect models, have allowed us to quantify differences in images from different subgroups of patients with multiple sclerosis (MS) and to determine the dependence of chemical pathology on clinical disability, duration of disease and lesions on T2‐weighted MRI. Statistical power was improved by using all reliable resonance intensities in the spectroscopic images while taking into consideration the intra‐subject correlations. We studied 17 normal subjects, 14 patients with relapsing remitting (RR) MS and 21 patients with chronic progressive (CP) MS. The ratio of resonance intensities of N‐acetylaspartate over creatine (Cr) was found to be significantly lower than normal in normal appearing white matter (NAWM) of both RR and CP patients (19.6% in RR, 28.8% in CP). NAA/Cr was decreased even more in MS plaques than in NAWM (44.2% in RR, 17.7% in CP). NAA/Cr was correlated with clinical disability (p<0.02) and disease duration (p<0.1). Our results suggest that, in this setting, MRS reflects accumulated neuronal loss or damage and can be used as a measure of disease severity. The methods developed provide opportunities to evaluate the relationship between inflammation, demyelination, axonal loss and clinical disability in future studies.
Characterization of Arabidopsis NEET Reveals an Ancient Role for NEET Proteins in Iron Metabolism[W]

This work describes biochemical, biophysical, structural, and genetic analyses of an Arabidopsis homolog of mammalian NEET proteins, which are involved in a wide range of cellular processes. It finds that At-NEET plays a key role in plant development, senescence, reactive oxygen species homeostasis, and iron metabolism. The NEET family is a newly discovered group of proteins involved in a diverse array of biological processes, including autophagy, apoptosis, aging, diabetes, and reactive oxygen homeostasis. They form a novel structure, the NEET fold, in which two protomers intertwine to form a two-domain motif, a cap, and a unique redox-active labile 2Fe-2S cluster binding domain. To accelerate the functional study of NEET proteins, as well as to examine whether they have an evolutionarily conserved role, we identified and characterized a plant NEET protein. Here, we show that the Arabidopsis thaliana At5g51720 protein (At-NEET) displays biochemical, structural, and biophysical characteristics of a NEET protein. Phenotypic characterization of At-NEET revealed a key role for this protein in plant development, senescence, reactive oxygen homeostasis, and Fe metabolism. A role in Fe metabolism was further supported by biochemical and cell biology studies of At-NEET in plant and mammalian cells, as well as mutational analysis of its cluster binding domain. Our findings support the hypothesis that NEET proteins have an ancient role in cells associated with Fe metabolism.
Material properties of bone in the femoral head treated with ibandronate and BMP‐2 following ischemic osteonecrosis

Bone morphogenetic protein (BMP)‐2 and ibandronate (IB) decrease the femoral head deformity following ischemic osteonecrosis of the femoral head (ONFH). The purpose of this study was to determine the effects of BMP‐2 and IB on the mineral content and nanoindentation properties of the bone following ONFH. ONFH was surgically induced in the femoral head of piglets. There were five groups: normal control, untreated, IB, BMP, and BMP + IB (n = 5/group). Backscattered electron imaging, Raman spectroscopy, and nanoindentation testing were performed. Both BMP and BMP + IB groups showed calcium content in the trabecular bone similar to the normal group, while the IB and no‐treatment groups showed a significant increase in the calcium content compared to the normal group. The carbonate content relative to phosphate was significantly increased in the IB and BMP + IB groups (p < 0.01) compared to the normal group. No significant difference was found between the BMP and the normal group. The nanoindentation modulus of the bone in the IB group was significantly increased compared to the normal group (p < 0.05). No significant differences were observed between the BMP and BMP + IB groups compared to the normal group. The nanoindentation hardness measurements in the IB group were also significantly increased compared to the BMP and BMP + IB groups (p < 0.05). In summary, trabecular bone treated with BMP or BMP + IB had material properties comparable to normal bone whereas the bone in the IB group retained the increased mineral content and the nanoindentation hardness found in the necrotic bone. Hence, BMP or BMP + IB better restores the normal mineral content and nanomechanical properties after ONFH than IB treatment alone. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1453–1460, 2017.
Association of 
Clostridium difficile infection with outcomes of hospitalized solid organ transplant recipients: results from the 2009 Nationwide Inpatient Sample database

Diarrhea is a frequent and potentially severe complication in solid organ transplant (SOT) recipients. One of the most common infectious etiologies of diarrhea in these patients is Clostridium difficile. Our objective was to investigate the association of C. difficile infection (CDI) with the outcomes of hospitalized SOT patients.
High-dose methylprednisolone in children with Crimean-Congo haemorrhagic fever

Treatment options for Crimean-Congo haemorrhagic fever (CCHF) are limited and based on general supportive managements. Thrombocytopenia is the major risk factor of CCHF. We report our experience with high-dose methylprednisolone (HDMP). This study included five patients with CCHF. Patients were given HDMP if there were findings compatible with virus-associated haemophagocytic syndrome and the effects of HDMP were evaluated. Following this, HDMP fever subsided and platelet counts increased within 24 hours. Leukocyte counts began to increase and visceral bleedings were improved. HDMP treatment was discontinued within approximately five days. After HDMP, only one patient required blood products. HDMP is effective in CCHF, especially on fever and platelet counts. Dependency on blood products was decreased. Further controlled randomized studies with large series are needed in order to analyse the timing and duration of HDMP treatment and its effect on outcome.
Political Institutions, Governance, and Consumption Expenditure in Developing Countries: A Panel Data Analysis

type="main"> This article aims at identifying the determinants of government expenditures of developing countries by placing emphasis on the political institutions and governance variables, which have not been addressed so much in the previous literature. Using a panel data analysis for 97 developing countries from the period 1984 to 2004, this study finds evidence that controlling for economic, social, and demographical factors, political institutional and governance variables significantly influence the consumption expenditure in developing countries. Political institutional variables such as the type of political ruling and political power in the parliament positively influence consumption expenditure; on the contrary, governance variables such as corruption influence negatively. Furthermore, we find that autocratic governments with military ruling are not particularly accommodative toward consumption expenditures as the public spending significantly shrinks under military dictatorship compared with other forms of governance. In order to check consistency of our findings, we ran alternative specifications as well as conducted extreme bound tests. Our results largely survived these tests showing robustness of our findings. (JEL E01, E02, E61, E62, H2, H4, H5, H6, O11, O5)
Does Pay Disparity Really Hamstring Team Performance? A Study of Professional Ice Hockey Players

Here, I employ an unbalanced panel of data from the National Hockey League (NHL) to examine the impact of pay disparity on team-cohesiveness. I find evidence to suggest the existence of a negative relationship between higher degrees of within-position pay disparity and team performance; the evidence reported here shows a simple monotonic elasticity of team performance with respect to pay disparity to be roughly 19%.
Rates and types of events reported to established incident reporting systems in two US hospitals

Background: US hospitals have had voluntary incident reporting systems for many years, but the effectiveness of these systems is unknown. To facilitate substantial improvements in patient safety, the systems should capture incidents reflecting the spectrum of adverse events that are known to occur in hospitals. Objective: To characterise the incidents from established voluntary hospital reporting systems. Design: Observational study examining about 1000 reports of hospitalised patients at each of two hospitals. Patients and setting: 16 575 randomly selected patients from an academic and a community hospital in the US in 2001. Main outcome measures: Rates of incidents reported per hospitalised patient and characteristics of reported incidents. Results: 9% of patients had at least one reported incident; 17 incidents were reported per 1000 patient-days in hospital. Nurses filed 89% of reports, physicians 1.9% and other providers 8.9%. The most common types were medication incidents (29%), falls (14%), operative incidents (15%) and miscellaneous incidents (16%); 59% seemed preventable and preventability was not clear for 32%. Among the potentially preventable incidents, 43% involved nurses, 16% physicians and 19% other types of providers. Qualitative examination of reports indicated that very few involved prescribing errors or high-risk procedures. Conclusions: Hospital reporting systems receive many reports, but capture a spectrum of incidents that differs from the adverse events known to occur in hospitals, thereby substantially underdetecting physician incidents, particularly those involving operations, high-risk procedures and prescribing errors. Increasing the reporting of physician incidents will be essential to enhance the effectiveness of hospital reporting systems; therefore, barriers to reporting such incidents must be minimised.
Twenty-million-year relationship between mammalian diversity and primary productivity.

At global and regional scales, primary productivity strongly correlates with richness patterns of extant animals across space, suggesting that resource availability and climatic conditions drive patterns of diversity. However, the existence and consistency of such diversity-productivity relationships through geological history is unclear. Here we provide a comprehensive quantitative test of the diversity-productivity relationship for terrestrial large mammals through time across broad temporal and spatial scales. We combine >14,000 occurrences for 690 fossil genera through the Neogene (23-1.8 million years ago) with regional estimates of primary productivity from fossil plant communities in North America and Europe. We show a significant positive diversity-productivity relationship through the 20-million-year record, providing evidence on unprecedented spatial and temporal scales that this relationship is a general pattern in the ecology and paleo-ecology of our planet. Further, we discover that genus richness today does not match the fossil relationship, suggesting that a combination of human impacts and Pleistocene climate variability has modified the 20-million-year ecological relationship by strongly reducing primary productivity and driving many mammalian species into decline or to extinction.
Osteoprotegerin is expressed in colon carcinoma cells.

BACKGROUND Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor family, is produced by various cell types and tissues and plays a key role in the physiological regulation of osteoclast differentiation and activity. Also, OPG is a soluble decoy receptor for tumor necrosis factor-related apoptosis-inducing factor (TRAIL). In the present study we investigated whether the human colon cancer cell lines HT-29 and SW-480 produce and secrete OPG in vitro. MATERIALS AND METHODS Expression of OPG mRNA was examined by RT-PCR. OPG protein was analysed by ELISA assay and immunostaining methods. The effect of OPG secretion on TRAIL-mediated apoptosis was also investigated. RESULTS By RT-PCR, it was demonstrated that mRNA transcripts for OPG were produced by both cell lines. By ELISA analysis, OPG was detected in the culture medium; and treatment of cells with proinflammatory cytokines TNF-alpha and IL-1beta increased OPG secretion significantly. Tumor xenografts in nude mice also were shown to express OPG by immunohistochemistry. When RANKL, which selectively binds OPG, was added to cell cultures along with recombinant TRAIL, apoptosis was shown to increase significantly. CONCLUSION These data indicate that OPG may be involved in tumorigenesis and the progression of colon cancer.
Impact of Local Decision Rules in Distributed Sensor Networks

In this paper, we analyze the impact of the local decision rules on the performance of a distributed sensor network. We do this by fixing the fusion rule to be one of the three common binary decision rules: majority voting, AND and OR rules, and optimizing the local decision rules with respect to the probability of error at the fusion center. We assume that the sensor observations are correlated and we consider the general case of heterogeneous (non-identical) sensors. We show that systems having different fusion rules can all provide similar performance if the local decision rules are chosen appropriately
Region of Epidural Blockade Determines Sympathetic and Mesenteric Capacitance Effects in Rabbits

Background The mechanisms producing hemodynamic changes during epidural anesthesia are incompletely understood. The role of capacitance changes in the splanchnic venous bed can be clarified by comparing blocks of differing segmental distributions. Specifically, we speculated that blocks that include the innervation to the mesenteric circulation alter hemodynamics, sympathetic activity, and venous capacitance to a greater extent than blocks without blockade of sympathetic nerves to this critical vascular bed.
‘There’s a Catch-22’ – The complexities of pain management for people with advanced dementia nearing the end of life: A qualitative exploration of physicians’ perspectives

Background: Pain management is a cornerstone of palliative care. The clinical issues encountered by physicians when managing pain in patients dying with advanced dementia, and how these may impact on prescribing and treatment, are unknown. Aim: To explore physicians’ experiences of pain management for patients nearing the end of life, the impact of these on prescribing and treatment approaches, and the methods employed to overcome these challenges. Design: Qualitative, semi-structured interview study exploring barriers to and facilitators of pain management, prescribing and treatment decisions, and training needs. Thematic analysis was used to elicit key themes. Setting/participants: A total of 23 physicians, responsible for treating patients with advanced dementia approaching the end of life, were recruited from primary care (n = 9), psychiatry (n = 7) and hospice care (n = 7). Results: Six themes emerged: diagnosing pain, complex prescribing and treatment approaches, side effects and adverse events, route of administration, importance of sharing knowledge and training needs. Knowledge exchange was often practised through liaison with physicians from other specialities. Cross-speciality mentoring and the creation of knowledge networks were believed to improve pain management in this patient population. Conclusion: Pain management in end-stage dementia is complex, requiring cross-population of knowledge between palliative care specialists and non-specialists, in addition to collateral information provided by other health professionals and patients’ families. Regular, cost- and time-effective mentoring and ongoing professional development are perceived to be essential in empowering physicians to meet clinical challenges in this area.
Ethanol Alters Kinetic Characteristics and Function of Striatal Morphine Receptors

Abstract: Morphine was shown to promote dopamine (DA) synthesis and release in mouse striatum, but mice rendered tolerant and dependent on ethanol were found to be less responsive to morphine's effects on striatal DA metabolism than control animals. Ethanol feeding also produced a change in the affinity of striatal “opiate” receptors for [3H]dihydromorphine, and these ethanol‐induced receptor changes may be responsible for the altered biological effect of morphine.
Bone morphological analyses in Spontaneously Diabetic Torii (SDT) fatty rats

The Spontaneously Diabetic Torii (SDT) fatty rat, a model for obese type 2 diabetes, shows bone quantitative abnormalities, namely low bone mineral density (BMD). The objective of this study was to evaluate bone morphological changes, in particular identifying the bone qualitative abnormalities, in the SDT fatty rat. Male SDT fatty rats showed increases in total trabecular area and trabecular number and decreases in trabecular thickness in cancellous bones of the proximal tibia, indicating trabecular miniaturization. The SDT fatty rat is useful for investigation of pathophysiological changes in bone quality in diabetic osteoporosis.