Miracle-dz/UniFAR-FTUs huggingface dataset:
Lameness is consistently better at predicting broiler chicken performance in mobility tests than other broiler characteristics

To determine whether lame broilers are in pain it is necessary to compare measures of lameness and mobility before and after analgesic treatment. Such measures should not be unduly affected by other bird characteristics. This study assessed the performance of lame (gait score, GS 3–4) and non-lame (GS 0–1) broilers using two mobility tests: (i) a novel test to assess broiler ability to access resources when housed in groups (Group Obstacle test); and (ii) a Latency-to-Lie (LTL) test. Outcome test measures included number of obstacle crossings, latency to cross an obstacle, and time taken to sit in shallow water. Associations between outcome test measures and other bird characteristics (established lameness risk-factors), including strain, sex, age, mass, contact dermatitis and pathology, were also investigated. The performance of high-GS and low-GS broilers differed in both mobility tests and no other bird characteristics were as consistent a predictor as lameness. This demonstrates that mobility impairments are closely related to lameness assessed using GS, and that there is a component of lameness that cannot be explained by other bird characteristics (eg being male and heavy). This component may represent pain or discomfort. Both mobility tests are suitable for further application with analgesic testing to classify lameness-associated pain in broilers.
A liver-on-a-chip platform with bioprinted hepatic spheroids

The inadequacy of animal models in correctly predicting drug and biothreat agent toxicity in humans has resulted in a pressing need for in vitro models that can recreate the in vivo scenario. One of the most important organs in the assessment of drug toxicity is liver. Here, we report the development of a liver-on-a-chip platform for long-term culture of three-dimensional (3D) human HepG2/C3A spheroids for drug toxicity assessment. The bioreactor design allowed for in situ monitoring of the culture environment by enabling direct access to the hepatic construct during the experiment without compromising the platform operation. The engineered bioreactor could be interfaced with a bioprinter to fabricate 3D hepatic constructs of spheroids encapsulated within photocrosslinkable gelatin methacryloyl (GelMA) hydrogel. The engineered hepatic construct remained functional during the 30 days culture period as assessed by monitoring the secretion rates of albumin, alpha-1 antitrypsin, transferrin, and ceruloplasmin, as well as immunostaining for the hepatocyte markers, cytokeratin 18, MRP2 bile canalicular protein and tight junction protein ZO-1. Treatment with 15 mM acetaminophen induced a toxic response in the hepatic construct that was similar to published studies on animal and other in vitro models, thus providing a proof-of-concept demonstration of the utility of this liver-on-a-chip platform for toxicity assessment.
Validation of scaffold design optimization in bone tissue engineering: finite element modeling versus designed experiments

This study reports the development of biological/synthetic scaffolds for bone tissue engineering (TE) via 3D bioplotting. These scaffolds were composed of poly(L-lactic-co-glycolic acid) (PLGA), type I collagen, and nano-hydroxyapatite (nHA) in an attempt to mimic the extracellular matrix of bone. The solvent used for processing the scaffolds was 1,1,1,3,3,3-hexafluoro-2-propanol. The produced scaffolds were characterized by scanning electron microscopy, microcomputed tomography, thermogravimetric analysis, and unconfined compression test. This study also sought to validate the use of finite-element optimization in COMSOL Multiphysics for scaffold design. Scaffold topology was simplified to three factors: nHA content, strand diameter, and strand spacing. These factors affect the ability of the scaffold to bear mechanical loads and how porous the structure can be. Twenty four scaffolds were constructed according to an I-optimal, split-plot designed experiment (DE) in order to generate experimental models of the factor-response relationships. Within the design region, the DE and COMSOL models agreed in their recommended optimal nHA (30%) and strand diameter (460 μm). However, the two methods disagreed by more than 30% in strand spacing (908 μm for DE; 601 μm for COMSOL). Seven scaffolds were 3D-bioplotted to validate the predictions of DE and COMSOL models (4.5–9.9 MPa measured moduli). The predictions for these scaffolds showed relative agreement for scaffold porosity (mean absolute percentage error of 4% for DE and 13% for COMSOL), but were substantially poorer for scaffold modulus (51% for DE; 21% for COMSOL), partly due to some simplifying assumptions made by the models. Expanding the design region in future experiments (e.g., higher nHA content and strand diameter), developing an efficient solvent evaporation method, and exerting a greater control over layer overlap could allow developing PLGA-nHA-collagen scaffolds to meet the mechanical requirements for bone TE.
Biofabrication of a co-culture system in an osteoid-like hydrogel matrix

Biofabrication aims to develop functional, biological constructs using automated processes (additive manufacturing, AM) involving different cell types and biomaterials (Groll et al 2016 Biofabrication 13001 1–6). As bone tissue is based on the crosstalk between osteoblasts and osteoclasts at least, evaluating cell–cell and cell–material interactions is of interest to understand bone remodeling. There is increasing interest in the role of osteoclasts not only considering bone resorption, but also their influence on the proliferation, migration and differentiation of osteoblasts. Osteoid-like, non-mineralized matrix is used here for the 3D cultivation of osteoblast and osteoclast progenitor cells to evaluate interactions in an early stage of bone formation. The AM technology bioplotting was used to tailor a 3D environment with defined properties. These results could be helpful to transfer this approach to the fabrication of bone tissue in regenerative medicine approaches. Gelatin is derived from collagen, which is the main phase of osteoid. Oxidized alginate–gelatin crosslinked hydrogel was used to immobilize osteoblastic (ST2) and osteoclastic (RAW) progenitor cells. Cell viability and number, the expression of different proteins like alkaline phosphatase (ALP), osteopontin (OPN) and tartrate resistant acid phosphatase (TRAP) were investigated. Release of vascular endothelial growth factor (VEGF) by the immobilized cells was analyzed. Microscopy techniques were used to evaluate cell morphology during an incubation period of 21 days. The biofabrication process was compatible with the cells. Cells migrated, proliferated and expressed their specific proteins indicating cell differentiation. The co-culture showed increased OPN concentration, which is a major protein of the osteoid involved in the mineralization process. TRAP activity was increased compared to single culture. ST2 single culture showed higher ALP activity compared to the co-culture. VEGF concentration of the co-culture was strongly increased. The results indicate the importance of using co-cultures to fabricate bone tissue by biofabrication. Especially the influence of the osteoblast/osteoclast crosstalk, in an early stage of bone formation, is shown here, using a 3D hydrogel based cell culture model created by biofabrication.
Respiratory health effects of nitrogen dioxide exposure and current guidelines

This article reviews (i) the role of nitrogen dioxide (NO2) in respiratory diseases, including asthma, and (ii) appraises whether current guidelines for NO2 confer an adequate margin of safety for asthmatics. Medline and Excerpta Medica (1966-1997) were searched to retrieve original epidemiological studies which examined the relationship between NO2 and respiratory diseases including asthma. Previously reported reviews of controlled clinical studies were also utilised. The results of this search were then related to current NO2 guidelines. The review of 23 outdoor and 36 indoor studies suggests that respiratory effects are associated with levels of NO2 that may be encountered in common domestic and outdoor settings. Meta-analyses of studies among the general population of children demonstrate a 20% increase in respiratory problems, including increases of asthma by 20%, and wheezing by 12% in households with gas cookers. Epidemiological evidence also indicates that hourly NO2 values of 80 ppb are likely to.
Individual Frailty Components and Mortality in Kidney Transplant Recipients

Background Frailty increases early hospital readmission and mortality risk among kidney transplantation (KT) recipients. Although frailty represents a high-risk state for this population, the correlates of frailty, the patterns of the 5 frailty components, and the risk associated with these patterns are unclear. Methods Six hundred sixty-three KT recipients were enrolled in a cohort study of frailty in transplantation (12/2008-8/2015). Frailty, activities of daily living (ADL)/instrumental ADL (IADL) disability, Centers for Epidemiologic Studies Depression Scale depression, education, and health-related quality of life (HRQOL) were measured. We used multinomial regression to identify frailty correlates. We identified which patterns of the 5 components were associated with mortality using adjusted Cox proportional hazards models. Results Frailty prevalence was 19.5%. Older recipients (adjusted prevalence ratio [PR], 2.22; 95% confidence interval [CI], 1.21-4.07) were more likely to be frail. The only other factors that were independently associated with frailty were IADL disability (PR, 3.22; 95% CI, 1.72-6.06), depressive symptoms (PR, 11.31; 95% CI, 4.02-31.82), less than a high school education (PR, 3.10; 95% CI, 1.30-7.36), and low HRQOL (fair/poor: PR, 3.71; 95% CI, 1.48-9.31). The most common pattern was poor grip strength, low physical activity, and slowed walk speed (19.4%). Only 2 patterns of the 5 components emerged as having an association with post-KT mortality. KT recipients with exhaustion and slowed walking speed (hazards ratio = 2.43; 95% CI, 1.17-5.03) and poor grip strength, exhaustion, and slowed walking speed (hazard ratio, 2.61; 95% CI, 1.14-5.97) were at increased mortality risk. Conclusions Age was the only conventional factor associated with frailty among KT recipients; however, factors rarely measured as part of clinical practice, namely, HRQOL, IADL disability, and depressive symptoms, were significant correlates of frailty. Redefining the frailty phenotype may be needed to improve risk stratification for KT recipients.
The International Liver Transplantation Society Living Donor Liver Transplant Recipient Guideline

Abstract Living donor liver transplantation (LDLT) has been increasingly embraced around the world as an important strategy to address the shortage of deceased donor livers. The aim of this guideline, approved by the International Liver Transplantation Society (ILTS), is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT. Recommendations were developed from an analysis of the National Library of Medicine living donor transplantation indexed literature using the Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care of living donor liver transplant recipients.
Recurrent cervical cancer in a patient who was compound heterozygous for UGT1A1*6 and UGT1A1*28 presenting with serious adverse events during irinotecan hydrochloride/nedaplatin therapy

There have been no case reports of the risk of serious adverse events associated with the administration of irinotecan hydrochloride (CPT‐11) in patients with gynecologic cancer who are compound heterozygous for UGT1A1*6 and UGT1A1*28. A 71‐year‐old patient presented with recurrent stage IIIb cervical cancer. Combined chemotherapy was initiated with CPT‐11 (60 mg/m2 on days 1 and 8) plus nedaplatin (NDP; 80 mg/m2 on day 1), with each cycle lasting for 28 days. The patient was a compound heterozygote for UGT1A1*6 and UGT1A1*28. Hematotoxic adverse events observed during the chemotherapy were grade 4 neutropenia, grade 3 anemia, and grade 4 thrombocytopenia, and the non‐hematotoxic adverse events were grade 3 diarrhea and grade 3 fatigue. The findings in this patient indicate that CPT‐11 should be administered with great care, even at a dose of 60 mg/m2, in patients receiving combined therapy with CPT‐11 and NDP who are compound heterozygous for UGT1A1*6 and UGT1A1*28.
Kininogen‐dependent antiphosphatidylethanolamine antibodies and autoantibodies to factor XII in patients with recurrent pregnancy losses

Factor XII, plasma prekallikrein and high‐molecular‐weight kininogen were first identified as coagulation proteins in the intrinsic pathway because patients deficient in these proteins had marked prolongation of in vitro surface‐activated coagulation time. However, deficiencies of these proteins are not associated with clinical bleeding. Paradoxically, studies suggest that these proteins have anticoagulant and profibrinolytic activities. In fact, association between deficiencies of these proteins and thrombosis has been reported. Recently, autoantibodies to these proteins and antiphospholipid antibodies are frequent coagulation‐related abnormalities found in unexplained recurrent aborters. Evidence has accumulated for the presence of the kallikrein–kininogen–kinin system in the fetoplacental unit. The contact system, or kallikrein–kininogen–kinin system, in the reproductive tract plays an essential roll in the regulation of thrombosis, hemostasis, angiogenesis and in the defense against invasive bacterial infection. Autoantibodies to these proteins may be associated with pregnancy losses due to disruption of this system. These possibilities will be reviewed, the functions of the individual components will be summarized, and their role in blood coagulation and pregnancy discussed.
Death during pregnancy: Thrombotic thrombocytopenic purpura or septic shock?

Yamamoto et al. reported recently in the January issue of this Journal a case of sudden death attributed to thrombotic thrombocytopenic purpura (TTP). An alternative diagnosis can be suggested. First, the cause of sudden death in this case can be due to none other but a critical cardiac disorder, because no pathological change was seen in organs with the exception of edema in lungs and brain. Results of electrocardiogram (EKG), troponin and brain natriuretic peptide (BNP) assays are not given in the paper, although they constitute clear indicators of cardiac involvement. It would also be interesting to know if multiple microthrombi were actually observed in myocardium capillaries, as it has been found in one in three among the patients who died from TTP. Second, another diagnosis can be proposed, that is, septic shock. Although fever has been reported as one of the five signs defining TTP, arterial hypotension is uncommon in TTP. Moreover, the association of fever, tachycardia, leucopenia and elevated C-reactive protein level, is highly suggestive of systemic inflammatory response syndrome, mainly due to sepsis, and even of septic shock when blood pressure is low. The absence of an overt focus of infection on admission cannot discard septic shock. Furthermore, results of coagulation parameters in plasma would be interesting to collect, that would help to conclude whether disseminated intravascular coagulation was present. It would also be relevant to know the levels of lactic acid, potassium and creatinine in the serum because these are commonly elevated in septic shock. Third, results of undetectable ADAMTS 13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) activity and positive ADAMTS 13 inhibitor cannot actually be sufficient to give definite indication for diagnosing TTP, since sepsis can completely mimic TTP and be associated with low ADAMTS 13 activity, and even with positive ADAMTS 13 inhibitor. In a series of 415 consecutive patients who had been clinically diagnosed as TTP, 31 (7%) showed a systemic infection; among them, 16 showed all the four signs defining TTP, four showed ADAMTS 13 activity below 10% and three had a positive ADAMTS 13 inhibitor. To conclude, it can be recommended to consider severe sepsis in every case in the diagnosis of TTP.
Cavitation bubble cluster activity in the breakage of kidney stones by lithotripter shockwaves.

BACKGROUND AND PURPOSE There is strong evidence that cavitation bubble activity contributes to stone breakage and that shockwave-bubble interactions are involved in the tissue trauma associated with shockwave lithotripsy. Cavitation control may thus be a way to improve lithotripsy. MATERIALS AND METHODS High-speed photography was used to analyze cavitation bubble activity at the surface of artificial and natural kidney stones during exposure to lithotripter shockwaves in vitro. RESULTS Numerous individual bubbles formed on the surfaces of stones, but these bubbles did not remain independent but rather combined to form clusters. Bubble clusters formed at the proximal and distal ends and at the sides of stones. Each cluster collapsed to a narrow point of impact. Collapse of the proximal cluster eroded the leading face of the stone, and the collapse of clusters at the sides of stones appeared to contribute to the growth of cracks. Collapse of the distal cluster caused minimal damage. CONCLUSION Cavitation-mediated damage to stones is attributable, not to the action of solitary bubbles, but to the growth and collapse of bubble clusters.
New cathinone-derived designer drugs 3-bromomethcathinone and 3-fluoromethcathinone: studies on their metabolism in rat urine and human liver microsomes using GC-MS and LC-high-resolution MS and their detectability in urine.

3-Bromomethcathinone (3-BMC) and 3-Fluoromethcathinone (3-FMC) are two new designer drugs, which were seized in Israel during 2009 and had also appeared on the illicit drug market in Germany. These two compounds were sold via the Internet as so-called "bath salts" or "plant feeders. " The aim of the present study was to identify for the first time the 3-BMC and 3-FMC Phase I and II metabolites in rat urine and human liver microsomes using GC-MS and LC-high-resolution MS (HR-MS) and to test for their detectability by established urine screening approaches using GC-MS or LC-MS. Furthermore, the human cytochrome-P450 (CYP) isoenzymes responsible for the main metabolic steps were studied to highlight possible risks of consumption due to drug-drug interaction or genetic variations. For the first aim, rat urine samples were extracted after and without enzymatic cleavage of conjugates. The metabolites were separated and identified by GC-MS and by LC-HR-MS. The main metabolic steps were N-demethylation, reduction of the keto group to the corresponding alcohol, hydroxylation of the aromatic system and combinations of these steps. The elemental composition of the metabolites identified by GC-MS could be confirmed by LC-HR-MS. Furthermore, corresponding Phase II metabolites were identified using the LC-HR-MS approach. For both compounds, detection in rat urine was possible within the authors' systematic toxicological analysis using both GC-MS and LC-MS(n) after a suspected recreational users dose. Following CYP enzyme kinetic studies, CYP2B6 was the most relevant enzyme for both the N-demethylation of 3-BMC and 3-FMC after in vitro-in vivo extrapolation.
Hospitalization Among Individuals Waitlisted For Kidney Transplant

Background For patients waitlisted for a deceased-donor kidney, hospitalization is associated with a lower likelihood of transplantation and worse posttransplant outcomes. However, individual-, neighborhood-, and regional-level risk factors for hospitalization throughout the waitlist period and specific causes of hospitalization in this population are unknown. Methods We used United States Renal Data System Medicare-linked data on patients waitlisted between 2005 and 2013 with continuous enrollment in Medicare parts A and B (n = 53 810) to examine the association between annual hospitalization rate and a variety of demographic, clinical, and social factors. We used multilevel multivariable ordinal logistic regression to estimate odds ratios. Results Factors associated with significantly increased hospitalization rates among waitlisted individuals included older age, female sex, more years on dialysis before waitlisting, tobacco use, panel-reactive antibody greater than 0, public insurance or no insurance at end-stage renal disease diagnosis, more regional acute care hospital beds, and urban residence (all P < 0.05). Among patients dialysis-dependent when waitlisted, individuals with arteriovenous fistulas were significantly less likely than individuals with indwelling catheters or grafts to be hospitalized (odds ratios, 0.79 and 0.82, respectively, both P < 0.001). The most common causes of hospitalization were complications related to devices, implants, and grafts; hypertension; and sepsis. Conclusions Individual- and regional-level variables were significantly associated with hospitalization while waitlisted, suggesting that personal, health system, and geographic factors may impact patients' risk. Conditions related to dialysis access and comorbidities were common hospitalization causes, underscoring the importance proper access management and care for additional chronic health conditions.
Informações em saúde: a importância dos inquéritos populacionais

Partindo-se do suposto de que as estatisticas de saude devem compor um conjunto organizado de dados provenientes dos registros civil, da producao de servicos, das bases de dados de morbi-mortalidade, procura-se enfatizar a necessidade de coletar dados sobre saude e uso de servicos de saude, que so podem ser gerados por inqueritos populacionais periodicos, complementando dessa forma as deficiencias das informacoes para monitorar e avaliar as condicoes de saude e o desempenho do sistema de saude brasileiro. Faz-se uma apresentacao dos inqueritos desenvolvidos em alguns paises, seus enfoques principais e as limitacoes mais gerais. Finalmente, apresenta-se a producao mais recente de documentos e revisoes internacionais sobre os mecanismos que vem sendo utilizados em outros paises para a formulacao de uma politica de informacao em saude como parte da agenda da reforma do setor saude, que poderiam de certa forma apontar para alguns caminhos no caso brasileiro.