Miracle-dz/UniFAR-FTUs huggingface dataset:
Rab5 Isoforms Specifically Regulate Different Modes of Endocytosis in Leishmania*

Differential functions of Rab5 isoforms in endocytosis are not well characterized. Here, we cloned, expressed, and characterized Rab5a and Rab5b from Leishmania and found that both of them are localized in the early endosome. To understand the role of LdRab5 isoforms in different modes of endocytosis in Leishmania, we generated transgenic parasites overexpressing LdRab5a, LdRab5b, or their dominant-positive (LdRab5a:Q93L and LdRab5b:Q80L) or dominant-negative mutants (LdRab5a:N146I and LdRab5b:N133I). Using LdRab5a or its mutants overexpressing parasites, we found that LdRab5a specifically regulates the fluid-phase endocytosis of horseradish peroxidase and also specifically induced the transport of dextran-Texas Red to the lysosomes. In contrast, cells overexpressing LdRab5b or its mutants showed that LdRab5b explicitly controls receptor-mediated endocytosis of hemoglobin, and overexpression of LdRab5b:WT enhanced the transport of internalized Hb to the lysosomes in comparison with control cells. To unequivocally demonstrate the role of Rab5 isoforms in endocytosis in Leishmania, we tried to generate null-mutants of LdRab5a and LdRab5b parasites, but both were lethal indicating their essential functions in parasites. Therefore, we used heterozygous LdRab5a+/− and LdRab5b+/− cells. LdRab5a+/− Leishmania showed 50% inhibition of HRP uptake, but hemoglobin endocytosis was uninterrupted. In contrast, about 50% inhibition of Hb endocytosis was observed in LdRab5b+/− cells without any significant effect on HRP uptake. Finally, we tried to identify putative LdRab5a and LdRab5b effectors. We found that LdRab5b interacts with clathrin heavy chain and hemoglobin receptor. However, LdRab5a failed to interact with the clathrin heavy chain, and interaction with hemoglobin receptor was significantly less. Thus, our results showed that LdRab5a and LdRab5b differentially regulate fluid phase and receptor-mediated endocytosis in Leishmania.
Severe Maternal Morbidity Among Delivery and Postpartum Hospitalizations in the United States

OBJECTIVES: To propose a new standard for monitoring severe maternal morbidity, update previous estimates of severe maternal morbidity during both delivery and postpartum hospitalizations, and estimate trends in these events in the United States between 1998 and 2009. METHODS: Delivery and postpartum hospitalizations were identified in the Nationwide Inpatient Sample for the period 1998–2009. International Classification of Diseases, 9th Revision codes indicating severe complications were used to identify hospitalizations with severe maternal morbidity and related in-hospital mortality. Trends were reported using 2-year increments of data. RESULTS: Severe morbidity rates for delivery and postpartum hospitalizations for the 2008–2009 period were 129 and 29, respectively, for every 10,000 delivery hospitalizations. Compared with the 1998–1999 period, severe maternal morbidity increased by 75% and 114% for delivery and postpartum hospitalizations, respectively. We found increasing rates of blood transfusion, acute renal failure, shock, acute myocardial infarction, respiratory distress syndrome, aneurysms, and cardiac surgery during delivery hospitalizations. Moreover, during the study period, rates of postpartum hospitalization with 13 of the 25 severe complications examined more than doubled, and the overall mortality during postpartum hospitalizations increased by 66% (P<.05). CONCLUSIONS: Severe maternal morbidity currently affects approximately 52,000 women during their delivery hospitalizations and, based on current trends, this burden is expected to increase. Clinical review of identified cases of severe maternal morbidity can provide an opportunity to identify points of intervention for quality improvement in maternal care. LEVEL OF EVIDENCE: III
Climate change effects on above- and below-ground interactions in a dryland ecosystem

Individual species respond to climate change by altering their abundance, distribution and phenology. Less is known, however, about how climate change affects multitrophic interactions, and its consequences for food-web dynamics. Here, we investigate the effect of future changes in rainfall patterns on detritivore–plant–herbivore interactions in a semiarid region in southern Spain by experimentally manipulating rainfall intensity and frequency during late spring–early summer. Our results show that rain intensity changes the effect of below-ground detritivores on both plant traits and above-ground herbivore abundance. Enhanced rain altered the interaction between detritivores and plants affecting flower and fruit production, and also had a direct effect on fruit and seed set. Despite this finding, there was no net effect on plant reproductive output. This finding supports the idea that plants will be less affected by climatic changes than by other trophic levels. Enhanced rain also affected the interaction between detritivores and free-living herbivores. The effect, however, was apparent only for generalist and not for specialist herbivores, demonstrating a differential response to climate change within the same trophic level. The complex responses found in this study suggest that future climate change will affect trophic levels and their interactions differentially, making extrapolation from individual species' responses and from one ecosystem to another very difficult.
Financial Statement Effects of Adopting IFRS: The Canadian Experience

Purpose The purpose of this study is to examine the effects of adopting International Financial Reporting Standards (IFRS) on financial statements of the largest Canadian firms (S&P/TSX 60) listed on the Toronto Stock Exchange (TSX). Design/methodology/approach This study investigates the financial statement effects of 46 companies from the S&P/TSX 60 index which report under IFRS in 2011 and switched to IFRS from CGAAP. This study used panel data analysis, which can be considered as more powerful when conducting cross-sectional and in time analysis among companies. Because of weakness of Cramer statistic on R-square, the authors used interaction terms as suggested by Hope (2007). Findings Consistent with the authors’ perceptions, this study finds that significant effects of adopting IFRS are associated with industry practices. The empirical results show that the adoption of IFRS in Canada created more relevant financial reporting for book value of equity and net income in the post-adoption periods. Originality/value This study should be of interest to the US regulators considering IFRS adoption by US publicly traded companies as well as to regulators, standard setters and listed companies in all countries worldwide that are in transition to IFRS.
The Eldicus prospective, observational study of triage decision making in European intensive care units. Part II: Intensive care benefit for the elderly*

Rationale:Life and death triage decisions are made daily by intensive care unit physicians. Admission to an intensive care unit is denied when intensive care unit resources are constrained, especially for the elderly. Objective:To determine the effect of intensive care unit triage decisions on mortality and intensive care unit benefit, specifically for elderly patients. Design:Prospective, observational study of triage decisions from September 2003 until March 2005. Setting:Eleven intensive care units in seven European countries. Patients:All patients >18 yrs with an explicit request for intensive care unit admission. Interventions:Admission or rejection to intensive care unit. Measurements and Main Results:Demographic, clinical, hospital, physiologic variables, and 28-day mortality were obtained on consecutive patients. There were 8,472 triages in 6,796 patients, 5,602 (82%) were accepted to the intensive care unit, 1,194 (18%) rejected; 3,795 (49%) were ≥65 yrs. Refusal rate increased with increasing patient age (18–44: 11%; 45–64: 15%; 65–74: 18%; 75–84: 23%; >84: 36%). Mortality was higher for older patients (18–44: 11%; 45–64: 21%; 65–74: 29%; 75–84: 37%; >84: 48%). Differences between mortalities of accepted vs. rejected patients, however, were greatest for older patients (18–44: 10.2% vs. 12.5%; 45–64: 21.2% vs. 22.3%; 65–74: 27.9% vs. 34.6%; 75–84: 35.5% vs. 40.4%; >84: 41.5% vs. 58.5%). Logistic regression showed a greater mortality reduction for accepted vs. rejected patients corrected for disease severity for elderly patients (age >65 [odds ratio 0.65, 95% confidence interval 0.55–0.78, p < .0001]) than younger patients (age <65 [odds ratio 0.74, 95% confidence interval 0.57–0.97, p = .01]). Conclusions:Despite the fact that elderly patients have more intensive care unit rejections than younger patients and have a higher mortality when admitted, the mortality benefit appears greater for the elderly. Physicians should consider changing their intensive care unit triage practices for the elderly. (Crit Care Med 2012; 40:132–138)
CHROMOSOME ABNORMALITIES IN INFANTILE AUTISM AND OTHER CHILDHOOD PSYCHOSES: A POPULATION STUDY OF 66 CASES

Sixty‐six psychotic children aged between two and 20 years, examined by the same child psychiatrist and diagnosed according to strict criteria as suffering from infantile autism, other psychoses and Asperger's syndrome, were examined with chromosomal cultures in folic‐acid deficient medium. 47 per cent of the children showed major or minor chromosomal aberrations. The infantile autistic group comprised a total population of autistic children. The fra(X)(q27) marker was séen in 25 per cent of autistic boys. A subgroup of children with the fra(X)(q27) abnormality, infantile autism, psychomotor epilepsy and brainstem dysfunction was identified. Other chromosome markers and abnormalities occurring in several cases included long Y chromosomes, fra(XXp22), fra(16Xq23) and fra(6Xq26). The results are discussed and correlated with certain clinical characteristics.
The Role of Target Firm Power in M&A Knowledge Transfer

Abstract This study examines the role of target firm power in mergers and acquisitions (M&As). We investigate the effects of the position, referent and expert bases of power of the target firm on reverse knowledge transfer. We test our hypotheses on a sample of 123 responses from 106 domestic and foreign acquisitions conducted by Finnish companies. We find that a moderate level of target firm power supports reverse knowledge transfer. Also, we show that referent and expert bases of power are particularly important in explaining the overall degree of target firm power. This study contributes to the M&A literature by elaborating on the role of target firm power.
Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in Peritoneal Sarcomatosis

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the treatment most likely to achieve prolonged survival for peritoneal surface disease from various primaries, yet management of peritoneal sarcomatosis is controversial as a result of the propensity of sarcomas for hematogenous spread and the paucity of effective chemotherapy. Therefore, we reviewed our experience in patients with sarcomatosis. A retrospective analysis of a prospective database of 990 procedures was performed. Eastern Cooperative Oncology Group, age, type of primary, resection status, morbidity, mortality, and outcomes were reviewed. Over 20 years, 17 cytoreductions for sarcomatosis were performed. After excluding patients with gastrointestinal stromal tumor or uterine leiomyosarcoma, 10 procedures performed in seven patients remained. Median follow-up was 84.8 months. R0/1 resection was achieved in 60 per cent. The 30-day morbidity was 50 per cent; no operative mortality rate was observed. R2 resection had no long-term survivors. The reason for death was peritoneal recurrence in 57 per cent. Median survival was 21.6 months and five-year survival was 43 per cent. Median survival for patients with peritoneal sarcomatosis treated with CRS-HIPEC is similar with the historical reported survival before introducing chemoperfusion. Although a complete cytoreduction is related to improved survival, the role of HIPEC in these patients is unknown. A multi-institutional review will help define the role of CRS-HIPEC in this population.
Acute Kidney Injury and In-Hospital Mortality after Coronary Artery Bypass Graft versus Percutaneous Coronary Intervention: A Nationwide Study

Background: Post-procedural acute kidney injury (AKI) is associated with significantly increased short- and long-term mortalities, and renal loss. Few studies have compared the incidence of post-procedural AKI and in-hospital mortality between 2 major modalities of revascularization - coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) - and results have been inconsistent. Methods: We generated a propensity score-matched cohort that includes a total of 286,670 hospitalizations with multi-vessel coronary disease undergoing CABG or PCI (2004-2012) from the National Inpatient Sample database. We compared incidence of AKI, AKI requiring renal replacement therapy (RRT), in-hospital mortality, hospital stay, and charges between CABG and PCI groups. Results: The incidence of AKI after CABG was higher than PCI (8.9 vs. 4.5%, OR 2.05, 95% CI 1.99-2.12, p < 0.001). The incidence of AKI requiring RRT was also higher after CABG (1.1 vs. 0.5%, OR 2.14, 95% CI 1.96-2.34, p < 0.001). Likewise, in-hospital mortality was higher after CABG than PCI (2.0 vs. 1.4%, OR 1.44, 95% CI 1.35-1.52, p < 0.001). Among patients with pre-existing chronic kidney disease (stages I-IV), those undergoing CABG was associated with 2.0-2.3-fold higher odds of developing AKI than those undergoing PCI. The patients treated with CABG had a significantly longer hospital stay and higher hospital charges. Conclusions: Patients undergoing CABG are associated with (1) increased risk of developing post-procedural AKI, (2) higher likelihood of receiving RRT, and (3) worse short-term survival. Long-term renal outcome remains to be studied.
Adult‐onset Krabbe disease presenting with an isolated form of peripheral neuropathy

Introduction: Adult‐onset Krabbe disease is clinically rare and usually affects the pyramidal tracts in the central nervous system. Patients develop a spastic gait, and peripheral neuropathy sometimes occurs simultaneously. Methods: A 55‐year‐old woman with consanguineous parents developed slowly progressive, asymmetric muscle weakness and atrophy in her forearms, while her ability to walk remained unaffected without pyramidal tract signs after onset at age 51 years. Results: Nerve conduction studies demonstrated an asymmetric demyelinating‐type peripheral neuropathy, and sural nerve biopsy documented reduced myelinated nerve fiber density with uniformly thin myelin sheaths, suggesting hypomyelination. Brain MRI demonstrated minor white‐matter injury along the optic radiations, which was associated with asymptomatic, mild, prolonged latency on visual evoked potentials. Laboratory analysis documented low enzyme activity of galactocerebrosidase (GALC) and a known mutation of the GALC gene. Conclusion: Isolated peripheral neuropathy occurs very rarely in adult‐onset Krabbe disease. Muscle Nerve 54: 152–157, 2016
Effects of oral anticoagulant therapy and haplotype 1 of the endothelial protein C receptor gene on activated protein C levels

Summary Oral anticoagulants (OACs) reduce activated protein C (APC) plasma levels less than those of protein C (PC) in lupus erythematosus and cardiac patients. Carriers of the H1 haplotype of the endothelial PC receptor gene (PROCR) have higher APC levels than non-carriers. We aimed to confirm these results in a large group of patients treated with OACs because of venous thromboembolism (VTE) and to assess whether the effect is influenced by the PROCR H1 haplotype. We evaluated APC, PC, and factor (F)II levels in 502 VTE patients (158 with and 344 without OACs) and in 322 healthy individuals. Mean APC, PC and FII levels were significantly lower in OAC patients than in patients not taking OACs. During anticoagulant therapy, the FII/PC ratios were independent of the PC values, whereas APC/FII and APC/PC ratios significantly increased when FII and PC levels decreased. Of the 22 OAC patients carrying the H1H1genotype, 11 (50%) showed APC/PCag ≥2.0 and 10 (45%) APC/ FIIag ratios ≥2.0, whereas for the 49 OAC patients non-carrying the H1 haplotype these figures were 6 (12%) and 4 (8%), respectively (p<0.001). Barium citrate adsorption of plasma from OAC patients showed that most of the circulating free and complexed APC, but only part of PCag, is fully carboxylated. In conclusion, during anticoagulant therapy VT patients have APC levels disproportionately higher than the corresponding PC levels, mainly due to the presence of the PROCR H1 haplotype. Furthermore, a sufficiently carboxylated PC Gla-domain seems to be essential for PC activation in vivo.
The Effect of Helicobacter pylori Eradication on Gastroesophageal Reflux Disease

Background The effect of Helicobacter pylori (H. pylori) eradication on gastroesophageal reflux disease is controversial. We aimed to investigate the effect of H. pylori eradication in this group of patients. Materials and Methods Thirty-four consecutive patients with H. pylori infection and reflux esophagitis (grade 1 or 2) were enrolled into the study. Twenty-four hour intra-esophageal pH recording and esophageal manometry were performed before and 3 months after eradication of H. pylori, which was achieved using lansoprazole 30 mg b.i. d. , amoxycillin 1 g b.i. d. , and clarithromycin 500 mg b.i. d. for 14 days. H. pylori was evaluated in biopsy specimens taken from the antrum and corpus by rapid urease test and by histopathologic examination before and 3 months after eradication. Results Eighteen patients (11 men and 7 women, median age 42 years) completed the study. Three months after the treatment, there was no significant change in any of the 24-hour esophageal pH recording parameters and mean lower esophageal sphincter resting pressure (P > 0.05). The percentage of total time esophageal pH <4 increased in 10 patients, and decreased in 8 patients. There was a significant decrease in the scores of heartburn and regurgitation (P < 0.01). Esophagitis persisted in 16 patients and disappeared in 2 patients. Esophagitis score decreased in 6 patients, and did not change in 12 patients (P < 0.05). Conclusion H. pylori eradication does not have any effect on gastroesophageal acid reflux in patients with reflux esophagitis 3 months after eradication, but significant improvement is achieved in some reflux associated symptoms.
Cellular Mechanism of Decreased Bone in Brtl Mouse Model of OI: Imbalance of Decreased Osteoblast Function and Increased Osteoclasts and Their Precursors

The Brtl mouse, a knock‐in model for moderately severe osteogenesis imperfecta (OI), has a G349C substitution in half of type I collagen α1(I) chains. We studied the cellular contribution to Brtl bone properties. Brtl cortical and trabecular bone are reduced before and after puberty, with BV/TV decreased 40–45%. Brtl ObS/BS is comparable to wildtype, and Brtl and wildtype marrow generate equivalent number of colony‐forming units (CFUs) at both ages. However, OcS/BS is increased in Brtl at both ages (36–45%), as are TRACP+ cell numbers (57–47%). After puberty, Brtl ObS/BS decreases comparably to wildtype mice, but osteoblast matrix production (MAR) decreases to one half of wildtype values. In contrast, Brtl OcS falls only moderately (∼16%), and Brtl TRACP staining remains significantly elevated compared with wildtype. Consequently, Brtl BFR decreases from normal at 2 mo to one half of wildtype values at 6 mo. Immunohistochemistry and real‐time RT‐PCR show increased RANK, RANKL, and osteoprotegerin (OPG) levels in Brtl, although a normal RANKL/OPG ratio is maintained. TRACP+ precursors are markedly elevated in Brtl marrow cultures and form more osteoclasts, suggesting that osteoclast increases arise from more RANK‐expressing precursors. We conclude that osteoblasts and osteoclasts are unsynchronized in Brtl bone. This cellular imbalance results in declining BFR as Brtl ages, consistent with reduced femoral geometry. The disparity in cellular number and function results from poorly functioning osteoblasts in addition to increased RANK‐expressing precursors that respond to normal RANKL/OPG ratios to generate more bone‐resorbing osteoclasts. Interruption of the stimulus that increases osteoclast precursors may lead to novel OI therapies.
Impact of prenatal diagnosis on survival and early neurologic morbidity in neonates with the hypoplastic left heart syndrome.

BACKGROUND Prenatal echocardiography can identify the fetus that has complex congenital heart disease and may improve early management and surgical outcome. Prenatal diagnosis may be particularly beneficial to patients who have hypoplastic left heart syndrome (HLHS) and who are at risk for hypoxic-ischemic insult at presentation. OBJECTIVES We sought to determine whether prenatal diagnosis reduces neurologic morbidity and operative mortality in patients who undergo palliative surgery for the HLHS. METHODS Data from all patients who had HLHS, except for those with lethal genetic anomalies, and who were admitted to our institution between July 1992 and September 1997 were analyzed to assess the impact of prenatal diagnosis on preoperative management, neurologic morbidity, and surgical mortality. The primary outcome measures were hospital mortality and the incidence of adverse neurologic events (seizure or coma). RESULTS There were 216 patients who had HLHS and were referred for surgical palliation, 79 (36.6%) of whom had been diagnosed prenatally. All patients who had been diagnosed prenatally were delivered in an advanced nursery and were started on prostaglandin E(1) on the first day of life. Patients whose HLHS was diagnosed postnatally were begun on prostaglandin E(1) later in life (median = day 2 [range = 1-28 days]). There were 4 preoperative deaths and 53 operative or postoperative deaths. Overall hospital mortality was 26.4% and did not differ between patients whose HLHS had been diagnosed prenatally and those whose HLHS had been diagnosed postnatally. With the use of multivariable analysis, prenatal diagnosis was associated with fewer adverse perioperative neurologic events in the patients whose HLHS had been diagnosed prenatally than in those whose HLHS had been diagnosed postnatally (odds ratio = 0.46). CONCLUSIONS These data suggest that prenatal diagnosis has a favorable impact on treatment of patients who have HLHS and are undergoing staged palliation and reduces early neurologic morbidity. Prenatal diagnosis was not associated with reduced hospital mortality. It is possible that prenatal diagnosis may improve long-term neurologic outcome.