Miracle-dz/UniFAR-FTUs huggingface dataset:
Mdm1 maintains endoplasmic reticulum homeostasis by spatially regulating lipid droplet biogenesis

Lipid droplets (LDs) serve as cytoplasmic reservoirs for energy-rich fatty acids (FAs) stored in the form of triacylglycerides (TAGs). During nutrient stress, yeast LDs cluster adjacent to the vacuole/lysosome, but how this LD accumulation is coordinated remains poorly understood. The ER protein Mdm1 is a molecular tether that plays a role in clustering LDs during nutrient depletion, but its mechanism of function remains unknown. Here, we show that Mdm1 associates with LDs through its hydrophobic N-terminal region, which is sufficient to demarcate sites for LD budding. Mdm1 binds FAs via its Phox-associated domain and coenriches with fatty acyl–coenzyme A ligase Faa1 at LD bud sites. Consistent with this, loss of MDM1 perturbs free FA activation and Dga1-dependent synthesis of TAGs, elevating the cellular FA level, which perturbs ER morphology and sensitizes yeast to FA-induced lipotoxicity. We propose that Mdm1 coordinates FA activation adjacent to the vacuole to promote LD production in response to stress, thus maintaining ER homeostasis.
3D Numerical Simulation of Reactive Extrusion Processes for Preparing PP/TiO2 Nanocomposites in a Corotating Twin Screw Extruder

To better understand the relationship between flow, mixing and reactions in the process of preparing PP/TiO2, a 3D numerical simulation in a co-rotating twin screw extruder (TSE) was firstly employed using commercial CFD code, ANSYS Polyflow. The effects of rotating speed of screws, stagger angle of knead blocks, inlet flow rate and initial temperature of barrel on the mixing and reaction process in the TSE were investigated. The results reveal that the studied operational and geometric parameters, which determine mixing efficiency, residence time distribution, and temperature of the flows in the TSE, affect the local species concentration, reaction time and reaction rate, and hence have great influences on the conversion rate. The results show that increasing the rotating speed and inlet flow rate can decrease the time for sufficient mixing, which is not conducive to intensive reaction, and increasing the stagger angle has the opposite effect. Moreover, the conversion rate greatly affected by the initial temperature of barrel.
Combined 5 x 2 cv F Test for Comparing Supervised Classification Learning Algorithms

Dietterich (1998) reviews five statistical tests and proposes the 5 x 2 cv t test for determining whether there is a significant difference between the error rates of two classifiers. In our experiments, we noticed that the 5 x 2 cv t test result may vary depending on factors that should not affect the test, and we propose a variant, the combined 5 x 2 cv F test, that combines multiple statistics to get a more robust test. Simulation results show that this combined version of the test has lower type I error and higher power than 5 x 2 cv proper.
Side Effects of CXC-Chemokine Receptor 4–Directed Endoradiotherapy with Pentixather Before Hematopoietic Stem Cell Transplantation

The chemokine receptor CXC-chemokine receptor 4 (CXCR4) is a transmembrane receptor involved in survival, proliferation, and dissemination of different cancers, including hematopoietic malignancies. Relapsed or refractory hematopoietic cancers are frequently resistant to conventional therapy, and novel highly active strategies are urgently needed. CXCR4-directed endoradiotherapy constitutes a highly promising targeted therapeutic concept. Here, we investigated the adverse effects of this novel treatment approach. Methods: Twenty-two patients with heavily pretreated lymphoproliferative or myeloid malignancies were treated with 177Lu- or 90Y-pentixather—a CXCR4-directed therapeutic radioligand—before conventional conditioning therapy followed by autologous or allogeneic hematopoietic stem cell transplantation. Twenty-five CXCR4-directed endoradiotherapies were administered to those patients. Adverse events occurring between endoradiotherapy and the start of conventional conditioning therapy were retrospectively analyzed and graded for the estimation of the safety profile. Results: CXCR4-directed endoradiotherapy with pentixather showed a favorable toxicity profile. As expected, the hematopoietic system was most affected, with all subjects developing cytopenias. Except for 1 acute kidney failure, grade 3, due to tumor lysis syndrome, overall nephro- and hepatotoxicity was low. Other higher-grade adverse events were either transient and resolved or easily manageable. Conclusion: Therapy with radiolabeled pentixather appears to be well tolerated and easily applicable when preceding conventional conditioning regimens for hematopoietic stem cell transplantation.
A dynamic power-law sexual network model of gonorrhoea outbreaks

Human networks of sexual contacts are dynamic by nature, with partnerships forming and breaking continuously over time. Sexual behaviours are also highly heterogeneous, so that the number of partners reported by individuals over a given period of time is typically distributed as a power-law. Both the dynamism and heterogeneity of sexual partnerships are likely to have an effect in the patterns of spread of sexually transmitted diseases. To represent these two fundamental properties of sexual networks, we developed a stochastic process of dynamic partnership formation and dissolution, which results in power-law numbers of partners over time. Model parameters can be set to produce realistic conditions in terms of the exponent of the power-law distribution, of the number of individuals without relationships and of the average duration of relationships. Using an outbreak of antibiotic resistant gonorrhoea amongst men have sex with men as a case study, we show that our realistic dynamic network exhibits different properties compared to the frequently used static networks or homogeneous mixing models. We also consider an approximation to our dynamic network model in terms of a much simpler branching process. We estimate the parameters of the generation time distribution and offspring distribution which can be used for example in the context of outbreak reconstruction based on genomic data. Finally, we investigate the impact of a range of interventions against gonorrhoea, including increased condom use, more frequent screening and immunisation, concluding that the latter shows great promise to reduce the burden of gonorrhoea, even if the vaccine was only partially effective or applied to only a random subset of the population.
Diagnostic and therapeutic values of intraoperative electrophysiological neuromonitoring during resection of intradural extramedullary spinal tumors: a single-center retrospective cohort and meta-analysis.

OBJECTIVEWith the advent of intraoperative electrophysiological neuromonitoring (IONM), surgical outcomes of various neurosurgical pathologies, such as brain tumors and spinal deformities, have improved. However, its diagnostic and therapeutic value in resecting intradural extramedullary (ID-EM) spinal tumors has not been well documented in the literature. The objective of this study was to summarize the clinical results of IONM in patients with ID-EM spinal tumors.METHODSA retrospective patient database review identified 103 patients with ID-EM spinal tumors who underwent tumor resection with IONM (motor evoked potentials, somatosensory evoked potentials, and free-running electromyography) from January 2010 to December 2015. Patients were classified as those without any new neurological deficits at the 6-month follow-up (group A; n = 86) and those with new deficits (group B; n = 17). Baseline characteristics, clinical outcomes, and IONM findings were collected and statistically analyzed. In addition, a meta-analysis in compliance with the PRISMA guidelines was performed to estimate the overall pooled diagnostic accuracy of IONM in ID-EM spinal tumor resection.RESULTSNo intergroup differences were discovered between the groups regarding baseline characteristics and operative data. In multivariate analysis, significant IONM changes (p < 0.001) and tumor location (thoracic vs others, p = 0.018) were associated with new neurological deficits at the 6-month follow-up. In predicting these changes, IONM yielded a sensitivity of 82.4% (14/17), specificity of 90.7% (78/86), positive predictive value (PPV) of 63.6% (14/22), negative predictive value (NPV) of 96.3% (78/81), and area under the curve (AUC) of 0.893. The diagnostic value slightly decreased in patients with schwannomas (AUC = 0.875) and thoracic tumors (AUC = 0.842). Among 81 patients who did not demonstrate significant IONM changes at the end of surgery, 19 patients (23.5%) exhibited temporary intraoperative exacerbation of IONM signals, which were recovered by interruption of surgical maneuvers; none of these patients developed new neurological deficits postoperatively. Including the present study, 5 articles encompassing 323 patients were eligible for this meta-analysis, and the overall pooled diagnostic value of IONM was a sensitivity of 77.9%, a specificity of 91.1%, PPV of 56.7%, and NPV of 95.7%. CONCLUSIONSIONM for the resection of ID-EM spinal tumors is a reasonable modality to predict new postoperative neurological deficits at the 6-month follow-up. Future prospective studies are warranted to further elucidate its diagnostic and therapeutic utility.
Attenuating effects of guanidinoacetic acid on preslaughter transport-induced muscle energy expenditure and rapid glycolysis of broilers.

This study evaluated the effects of dietary guanidinoacetic acid (GAA) supplementation on growth performance, plasma variables, muscle energy status, glycolytic potential, and meat quality of broilers experiencing transport stress during the summer. A total of 320 28-day-old male Arbor Acres broilers were randomly allotted to 3 dietary treatments, including a GAA-free basal control diet (160 birds) and basal diet supplementation with 600 (80 birds) or 1,200 mg/kg (80 birds) GAA for 14 D. On the morning of day 42, after an 8-h fast, the birds fed basal diets were divided into 2 equal groups, and all birds in the 4 groups of 80 birds were transported according to the following protocols: 1) a 0.5-h transport of birds on basal diets (as a lower-stress control group), 2) a 3-h transport of birds on basal diets, and a 3-h transport of birds on basal diets supplemented with either 3) 600 or 4) 1,200 mg/kg GAA. The results revealed that dietary supplementation with GAA at 600 and 1,200 mg/kg for 14 D prior to slaughter did not affect growth performance, carcass traits, and most textural characteristics and chemical composition of the pectoralis major (PM) muscle (P > 0.05). In the GAA-free group, a 3-h transport increased the broiler live weight loss, elevated the plasma corticosterone concentration, decreased the plasma glucose concentration, muscle concentrations of ATP, creatine and energy charge value, increased the muscle AMP concentration and AMP/ATP ratio, and accelerated glycolysis metabolism, which resulted in inferior meat quality (lower pH and higher drip loss, P < 0.05). However, dietary addition of GAA at 1,200 mg/kg increased the mRNA expression of S-adenosyl-l-methionine: N-guanidino-acetate methyltransferase in the liver and creatine transporter in both the liver and PM muscle. It also elevated muscle concentrations of creatine and phosphocreatine (P < 0.05), which helps improve meat quality by ameliorating the 3-h transport-induced muscle energy expenditure and delaying anaerobic glycolysis of broilers.
In vitro and in silico hormonal activity studies of di‐(2‐ethylhexyl)terephthalate, a di‐(2‐ethylhexyl)phthalate substitute used in medical devices, and its metabolites

Plasticizers added to polyvinylchloride used in medical devices can be released into patients’ biological fluids. The substitution of di‐(2‐ethylhexyl)phthalate (DEHP) by alternative plasticizers is essential but their safety must be demonstrated. DEHP, di‐(2‐ethylhexyl)terephthalate (DEHT) and their metabolites were investigated using level 2 Organization for Economic Co‐operation and Development bioassays to screen for in vitro hormonal changes. Differences between the DEHP and DEHT metabolites were observed. Albeit weak, the hormonal activities of DEHT‐derived metabolites, e.g., 5‐OH metabolite of mono‐(ethylhexyl)terephthalate (5‐OH‐MEHT), were detected and the results of docking experiments performed on estrogen receptor alpha and androgen receptor agreed with the biological results. A co‐stimulation of human estrogen receptor alpha and human androgen receptor was also observed. With regard to steroidogenesis, a 16‐fold increase in estrogen synthesis was measured with 5‐OH‐MEHT. Therefore, even if DEHT remains an interesting alternative to DEHP because of its low migration from medical devices, it seems important to verify that multi‐exposed patients in neonatal intensive care units do not have urinary levels of oxidized metabolites, in particular 5‐OH‐MEHT, suggesting a potential endocrine‐disrupting effect.
Palliative hemispherotomy in children with bilateral seizure onset.

OBJECT Intractable epilepsy is a significant burden on families and on the cognitive development and quality of life (QOL) of patients. Periinsular hemispherotomy (PIH) for medically intractable epilepsy can benefit patients who qualify for this procedure. The ideal hemispherotomy candidate has ipsilateral ictal and interictal epileptiform activity, unilateral MR imaging abnormalities, contralateral hemiplegia, and a normal contralateral hemisphere. However, certain patients present with a mixed picture of bilateral electroencephalography (EEG) findings and severe intractable epilepsy, prompting consideration of a more aggressive treatment approach. This report introduces the possibility of surgery for patients who normally would not meet criteria for this treatment modality. METHODS In this retrospective chart review, the authors report on 7 patients with bilateral seizure onset noted on routine or video-EEG monitoring. A QOL phone questionnaire, based on the Quality of Life in Childhood Epilepsy tool, was administered to a parent. The authors reviewed each patient's chart for surgical complications, changes in examination, QOL, limited neuropsychological outcomes, and seizure outcomes. They also investigated each chart for MR imaging and EEG findings as well as the patient's epilepsy clinic notes for seizure semiology and frequency. RESULTS All patients enjoyed a decrease in seizure frequency and a subjective increase in QOL after PIH. Five patients (71%) achieved Engel Class I or II seizure control. The mean follow-up was 3.64 years (2-5.3 years). One patient is now off all antiseizure medication. No patient had a decrement in Full Scale IQ on postsurgical testing, and 2 (28.5%) of 7 individuals had increased adaptive and social functioning. Postsurgical examination changes included hemiplegia and homonymous hemianopia. CONCLUSIONS Hemispherotomy in patients with intractable epilepsy is generally reserved for individuals with unilateral epileptiform abnormalities or lesions on MR imaging. Seven patients in this study benefited from surgery despite bilateral seizure onset with improvement in seizure control and overall QOL. Thus, bilateral ictal onset does not necessarily preclude consideration for hemispherotomy in selected patients with severe medically refractory epilepsy.
Socio-demographic and clinical determinants of late presentation among patients newly diagnosed with HIV in the Eastern Cape, South Africa

Abstract South Africa recently implemented the ‘test and treat’ strategy for all HIV-infected individuals receiving diagnosis at the health facility level. However, the impact of this programme in terms of the prevention of HIV transmission, morbidity and mortality associated with HIV can only be maximized if patients are diagnosed early. This study determines the prevalence of late presentation among newly diagnosed HIV-infected individuals and also examines the socio-demographic and clinical determinants for late presentation in health facilities in the Eastern Cape Province, South Africa. In this cross-sectional study, a total of 335 newly diagnosed patients were recruited consecutively between August 2016 and July 2017. Late presenter for HIV care was defined in accordance with the European Late Presenter Consensus working group as a patient who reports for care when the CD4 count is below 350 cells/&mgr;L and/or when there is an established AIDS-defining clinical condition, irrespective of CD4 count. Adjusted and unadjusted logistic regression analysis was used to examine the determinants of late HIV diagnosis. Participants’ mean age was 33.6 (SD: 10.6). Almost 96% of the participants believed their route of HIV infection was heterosexual sex. Most newly diagnosed HIV-infected patients (60%) were late presenters (CD4+ count ⩽350 cells/&mgr;L and/or having an AIDS-defining illness in World Health Organisation (WHO)-defined stage III/IV), with 35% presenting with Acquired Immune Deficiency Syndrome (AIDS)-related complications. In the adjusted model, only male sex (AOR: 2.81; CI: 1.51–5.23), no formal education (AOR: 5.63; CI: 1.68–18.85), and overweight body mass category (AOR: 2.45; CI: 1.04–5.75) were independently associated with late HIV diagnosis. The majority of newly diagnosed HIV-infected individuals were late presenters. To maximize the impact of the ‘test and treat’ policy aimed at reducing new HIV transmissions and preventing the morbidity and mortality associated with HIV, there is a need for programmes to improve early detection of HIV in the study settings. This programme should target males and individuals with no formal education for maximum impact.
Proteomic Analysis of Intraluminal Thrombus Highlights Complement Activation in Human Abdominal Aortic Aneurysms

Objective—To identify proteins related to intraluminal thrombus biological activities that could help to find novel pathological mechanisms and therapeutic targets for human abdominal aortic aneurysm (AAA). Approach and Results—Tissue-conditioned media from patients with AAA were analyzed by a mass spectrometry–based strategy using liquid chromatography coupled to tandem mass spectrometry. Global pathway analysis by Ingenuity software highlighted the presence of several circulating proteins, among them were proteins from the complement system. Complement C3 concentration and activation were assessed in plasma from AAA patients (small AAA, AAA diameter=3–5 cm and large AAA, AAA diameter >5 cm), showing decreased C3 levels and activation in large AAA patients. No association of a combination of single-nucleotide polymorphisms in complement genes between large and small AAA patients was observed. Intense extracellular C3 inmunostaining, along with C9, was observed in AAA thrombus. Analysis of C3 in AAA tissue homogenates and tissue-conditioned media showed increased levels of C3 in AAA thrombus, as well as proteolytic fragments (C3a/C3c/C3dg), suggesting its local deposition and activation. Finally, the functional role of local complement activation in polymorphonuclear (PMN) cell activation was tested, showing that C3 blockade by anti-C3 antibody was able to decrease thrombus-induced neutrophil chemotaxis and reactive oxygen species production. Conclusions—A decrease of systemic C3 concentration and activity in the later stages of AAA associated with local complement retention, consumption, and proteolysis in the thrombus could induce PMN chemotaxis and activation, playing a detrimental role in AAA progression.
Management of residual masses in testicular germ cell tumors

ABSTRACT Introduction: About 50% of all patients with advanced testicular cancer demonstrate residual retroperitoneal or extraretroperitoneal masses. About two thirds of the masses harbour necrosis/fibrosis only whereas as about 10% and 40% harbour vital cancer or teratoma. Appropriate therapy will result in a high cure rate if performed properly. Areas covered: This review article covers the indication, the surgical technique and the oncological outcome of PC-RPLND and resection of extraretroperitoneal residual masses following chemotherapy in patients with advanced testis cancer. Expert commentary: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) plays an integral part of the multimodality treatment in patients with advanced testicular germ cell tumours. Patients with nonseminomas, residual masses < 1cm and good prognosis can undergo active surveillance. In all other cases, PC-RPLND with or without resection of adjacent organs needs to be performed for curative intent. PC-RPLND requires a complex surgical approach and should be performed in experienced, tertiary referral centres only.
The state of social care: the reality of a fragmented system.

Some clinical commissioning groups, handed responsibilities by the 2012 Health and Social Care Act, were convinced that proactive, integrated care closer to home was the answer. Inspired by reported success in places such as Torbay,1 GPs were going to wrap a holistic package of health and social care around frail older people. They predicted that patients and their families would plan for crises in advance and hospital admissions would fall. Frail older patients would be discharged earlier and delayed transfers of care would be a thing of the past, with Emergency Frailty Units providing rapid and comprehensive geriatric assessment with early discharge home. Joining with social care in a virtuous circle of quality improvement, hundreds of hospital beds could be closed and the money invested in care closer to home. Local authorities with social care responsibilities put in place a range of programmes to reduce costs, review commissioning, and coordinate services across public health and social care. NHS Better Care Funds were settled on social care departments. Many wished this engagement might lead to marriage and sustainability ever after. Draft NHS Sustainability and Transformation Plans (STP) built on these foundations. Leicestershire’s was published in November 2016 and promised the closure of 281 hospital and community beds. They would not be needed. Allied to Better Care, Leicestershire’s ambitious new Help to Live at Home service was launched in November 2016. Rather than spot-purchasing personal social care packages from a multiplicity of small providers, Leicestershire County Council (LCC) rationalised its contracts, giving responsibility for one district to one provider. This innovative service model would enable a stronger relationship between the purchaser and provider. It would facilitate …
Neutron-induced Rat Mammary Carcinomas Are Mainly of Luminal Subtype and Have Multiple Copy Number Aberrations

Background/Aim: Neutrons are used as a type of high linear energy transfer (LET) radiation and they have stronger carcinogenic effects compared to low LET radiation. We sought to clarify the features of mammary carcinomas for which the incidence increases when these were exposed to neutron radiation. Materials and Methods: We compared mammary carcinomas from female Sprague-Dawley rats irradiated at 7 weeks of age with 0.485 Gy neutron beams or 0.5-Gy γ rays, with carcinomas of non-irradiated rats. Tumors were classified into luminal and non-luminal subtypes based on immunohistochemistry, while their copy number aberrations were determined using microarrays. Results: Neutrons and γ rays significantly increased the incidence of luminal carcinomas. The carcinomas in the three groups contained multiple aberrations affecting 46 genes for which mutations have been reported in human breast cancer. Conclusion: Neutrons and γ rays increase the incidence of luminal mammary carcinoma in rats, probably via genetic aberrations similar to those found in human breast cancer patients.