bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of a model for equine small intestinal disease: effects of extracorporeal blood perfusion of equine ileum on metabolic variables and histological morphology – an experimental ex vivo study
Authors: Unterköfler Maria S. , McGorum Bruce C. , Milne Elspeth M. , Licka Theresia F. 
Published: November 2019

AbstractBackgroundIn horses a number of small intestinal diseases is potentially life threatening. Among them are Equine Grass Sickness (EGS), which is characterised by enteric neurodegeneration of unknown aetiology, as well as reperfusion injury of ischaemic intestine (I/R), and post-operative ileus (POI), common after colic surgery. The perfusion of isolated organs is successfully used to minimize animal testing for the study of pathophysiology in other scenarios. However, extracorporeal perfusion of equine ileum sourced from horses slaughtered for meat production has not yet been described. Therefore the present study evaluated the potential of such a model for the investigation of small intestinal diseases in an ex vivo and cost-efficient system avoiding experiments in live animals.ResultNine ileum specimens were sourced from horses aged 1–10 years after routine slaughter at a commercial abattoir. Ileum perfusion with oxygenated autologous blood and plasma was successfully performed for 4 h in a warm isotonic bath (37.0–37.5 °C). Ileum specimens had good motility and overall pink to red mucosa throughout the experiment; blood parameters indicated good tissue vitality: 82 ± 34 mmHg mean arterial partial pressure of oxygen (pO2) compared to 50 ± 17 mmHg mean venous pO2,48 ± 10 mmHg mean arterial partial pressure of carbon dioxide (pCO2) compared to 66 ± 7 mmHg venous pCO2and 9.8 ± 2.8 mmol/L mean arterial lactate compared to 11.6 ± 2.7 mmol/L venous lactate. There was a mild increase in ileum mass reaching 105 ± 7.5% of the pre-perfusion mass after 4 hours. Histology of haematoxylin and eosin stained biopsy samples taken at the end of perfusion showed on average 99% (±1%) histologically normal neurons in the submucosal plexus and 76.1% (±23.9%) histologically normal neurons in the myenteric plexus and were not significantly different to control biopsies.ConclusionExtracorporeal, normothermic perfusion of equine ileum over 4 h using autologous oxygenated blood/plasma perfusate showed potential as experimental model to test whether haematogenous or intestinal exposure to neurotoxins suspected in the pathogenesis of EGS can induce neuronal damage typical for EGS. Also, this model may allow investigations into the effect of pharmaceuticals on I/R injury, as well as into the pathogenesis of equine POI.
ATM controls DNA repair and mitochondria transfer between neighboring cells
Authors: Jin Sha , Cordes Nils 
Published: November 2019

Abstract
Intercellular communication is essential for multicellular tissue vitality and homeostasis. We show that healthy cells message protective signals through direct cell–cell connections to adjacent DNA–damaged cells in a microtubule–dependent manner. In DNA–damaged cells, mitochondria restoration is facilitated by fusion with undamaged mitochondria from healthy cells and their DNA damage repair is optimized in presence of healthy cells. Both, mitochondria transfer and intercellular signaling for an enhanced DNA damage response are critically regulated by the activity of the DNA repair protein ataxia telangiectasia mutated (ATM). These healthy–to–damaged prosurvival processes sustain normal tissue integrity and may be exploitable for overcoming resistance to therapy in diseases such as cancer.
Pathological pain processing in mouse models of multiple sclerosis and spinal cord injury: contribution of plasma membrane calcium ATPase 2 (PMCA2)
Authors: Mirabelli Ersilia , Ni Li , Li Lun , Acioglu Cigdem , Heary Robert F. , Elkabes Stella 
Published: November 2019

AbstractBackgroundNeuropathic pain is often observed in individuals with multiple sclerosis (MS) and spinal cord injury (SCI) and is not adequately alleviated by current pharmacotherapies. A better understanding of underlying mechanisms could facilitate the discovery of novel targets for therapeutic interventions. We previously reported that decreased plasma membrane calcium ATPase 2 (PMCA2) expression in the dorsal horn (DH) of healthy PMCA2+/−mice is paralleled by increased sensitivity to evoked nociceptive pain. These studies suggested that PMCA2, a calcium extrusion pump expressed in spinal cord neurons, plays a role in pain mechanisms. However, the contribution of PMCA2 to neuropathic pain processing remains undefined. The present studies investigated the role of PMCA2 in neuropathic pain processing in the DH of wild-type mice affected by experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and following SCI.MethodsEAE was induced in female and male C57Bl/6N mice via inoculation with myelin oligodendrocyte glycoprotein fragment 35–55 (MOG35–55) emulsified in Complete Freund’s Adjuvant (CFA). CFA-inoculated mice were used as controls. A severe SC contusion injury was induced at thoracic (T8) level in female C57Bl/6N mice. Pain was evaluated by the Hargreaves and von Frey filament tests. PMCA2 levels in the lumbar DH were analyzed by Western blotting. The effectors that decrease PMCA2 expression were identified in SC neuronal cultures.ResultsIncreased pain in EAE and SCI was paralleled by a significant decrease in PMCA2 levels in the DH. In contrast, PMCA2 levels remained unaltered in the DH of mice with EAE that manifested motor deficits but not increased pain. Interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), and IL-6 expression were robustly increased in the DH of mice with EAE manifesting pain, whereas these cytokines showed a modest increase or no change in mice with EAE in the absence of pain. Only IL-1β decreased PMCA2 levels in pure SC neuronal cultures through direct actions.ConclusionsPMCA2 is a contributor to neuropathic pain mechanisms in the DH. A decrease in PMCA2 in DH neurons is paralleled by increased pain sensitivity, most likely through perturbations in calcium signaling. Interleukin-1β is one of the effectors that downregulates PMCA2 by acting directly on neurons.
Reduction of dose to duodenum with a refined delineation method of Para-aortic region in patients with locally advanced cervical Cancer receiving prophylactic extended-field radiotherapy
Authors: Yang Bo , Liu Xiaoliang , Hu Ke , Qiu Jie , Zhang Fuquan , Hou Xiaorong , Yan Junfang , Meng Qingyu , Wang Weiping , Yu Lang , Wang Yijun 
Published: November 2019

Abstract

Background
To compare irradiation dose to the second and third portions of duodenum (Duo2 and Duo3) with a new refined and old delineation method of para-aortic region for patients with locally advanced cervical cancer (LACC) receiving prophylactic extended-field radiotherapy (EFRT).

Methods
Twenty consecutive patients with LACC were treated with prophylactic EFRT from January 2016 to January 2017 at our institute. Two delineation methods of para-aortic region were designed for each patient, the old delineation method ensured a full coverage of aortic and inferior vena cava, while the right paracaval region above L3 was omitted from CTV in the new delineation method. Patients received a dose of 50.4Gy in 28 fractions for PCTV and a dose of 60.2Gy in 28 fractions for PGTV with volumetric-modulated arc therapy (VMRT). The dose delivered to Duo2 and Duo3 with these two delineation methods were compared.

Results
All treatment plans achieved excellent target volume coverage with 95% of PCTV receiving 50.4Gy and 95% of PGTV receiving 60.2Gy. There was no difference between delineation methods in low dose level (V5, V10, V15, V20, V25) for Duo2 and Duo3. The V30, V35, V40, V45, V50, Dmax, Dmean and D2cc for Duo2 with the new and old delineation methods were 55.76% vs 80.54% (P = 0.009), 34.72% vs 70.91% (P < 0.001), 18.69% vs 55.46% (P < 0.001), 8.20% vs 41.49% (P < 0.001), 1.86% vs 21.60% (P < 0.001), 49.58Gy vs 52.91Gy (P = 0.002), 30.38Gy vs 39.22Gy (P = 0.001) and 37.90Gy vs 48.64Gy (P < 0.001) respectively. For Duo3, the new delineation method achieved significant advantages in V30, V35, V40, V45, V50 and Dmean over the old one (96.82% vs 99.25%, P = 0.021; 89.65% vs 97.21%, P = 0.001; 79.50% vs 93.18%, P < 0.001; 65.63% vs 82.93%, P < 0.001; 43.39% vs 65.60%, P < 0.001; 46.09Gy vs 49.24Gy, P < 0.001), no deference was observed regarding D2cc and Dmax with these two delineation methods.

Conclusion
With the new delineation method of para-aortic area in prophylactic EFRT, significant reduction of irradiation dose to the second and third portions of duodenum in high dose area was obtained. This may further lower the incidence of duodenal toxicity when performing prophylactic EFRT for patients with LACC.
Reducing complexity: explaining inborn errors of metabolism and their treatment to children and adolescents
Authors: Zeltner Nina A. , Welsink-Karssies Mendy M. , Landolt Markus A. , Bosshard-Bullinger Dominique , Keller Fabia , Bosch Annet M. , Groenendijk Marike , Grünert Sarah C. , Karall Daniela , Rettenbacher Beatrix , Scholl-Bürgi Sabine , Baumgartner Matthias R. , Huemer Martina 
Published: November 2019

Abstract

Background
Inborn errors of metabolism (IEM) are a group of rare, heterogeneous and complex genetic conditions. Clinically, IEM often affect the central nervous system and other organs. Some carry the risk of progression and / or potentially life-threatening crises. Many patients have to adhere to lifelong dietary or drug treatment.
The complexity of IEM makes it difficult for patients and caregivers to understand their pathophysiology, inheritance and therapy rationale. Especially patients reaching adolescence may have only limited knowledge of their condition since medical care has often entirely been handled by their parents. Knowledge about disease and treatment, however, constitute pillars of self-responsible disease management. Not many standardized patient education materials on IEM are available and their comprehensibility has not been systematically investigated.

Methods
We developed and tested patient education materials for school-aged children and adolescents with IEM. Informative texts and illustrations in paper form and as videos were developed by an international network of metabolic care professionals together with a graphic artist and experts for easy-to-read language. The materials were presented in standardized single or group training sessions to 111 individuals; first, to 74 healthy children and adolescents (recruited via public schools) and consecutively to 37 paediatric patients with IEM (phenylketonuria, galactosemia, urea cycle defects, lysosomal storage disorders) from six metabolic centres. Knowledge-gain was assessed by pre- and post-testing.

Results
Knowledge-gain was significant in healthy children and adolescents as well as in patients (p < .001, r =. -77 /. -70). Effect sizes were large in both groups (r = -.77 / -.70). This result was independent from family language and teacher-rated concentration or cognitive capacity in healthy children.

Conclusion
The newly developed patient education materials are a powerful tool to improve disease- and treatment-related knowledge. They facilitate communication between the medical team and children and adolescents with IEM and their caregivers.
C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy
Authors: Garam Nóra , Prohászka Zoltán , Szilágyi Ágnes , Aigner Christof , Schmidt Alice , Gaggl Martina , Sunder-Plassmann Gere , Bajcsi Dóra , Brunner Jürgen , Dumfarth Alexandra , Cejka Daniel , Flaschberger Stefan , Flögelova Hana , Haris Ágnes , Hartmann Ágnes , Heilos Andreas , Mueller Thomas , Rusai Krisztina , Arbeiter Klaus , Hofer Johannes , Jakab Dániel , Sinkó Mária , Szigeti Erika , Bereczki Csaba , Janko Viktor , Kelen Kata , Reusz György S. , Szabó Attila J. , Klenk Nóra , Kóbor Krisztina , Kojc Nika , Knechtelsdorfer Maarten , Laganovic Mario , Lungu Adrian Catalin , Meglic Anamarija , Rus Rina , Kersnik-Levart Tanja , Macioniene Ernesta , Miglinas Marius , Pawłowska Anna , Stompór Tomasz , Podracka Ludmila , Rudnicki Michael , Mayer Gert , Romana Rysava  , Reiterova Jana , Saraga Marijan , Tomáš Seeman  , Zieg Jakub , Sládková Eva , Szabó Tamás , Capitanescu Andrei , Stancu Simona , Tisljar Miroslav , Galesic Kresimir , Tislér András , Vainumäe Inga , Windpessl Martin , Zaoral Tomas , Zlatanova Galia , Csuka Dorottya 
Published: November 2019

AbstractBackgroundAcquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors.ResultsOne hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 nephritic factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of nephritic factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF.ConclusionsIn conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10–15% of IC-MPGN/C3G patients.
Reduced sphingolipid hydrolase activities, substrate accumulation and ganglioside decline in Parkinson’s disease
Authors: Huebecker Mylene , Moloney Elizabeth B. , van der Spoel Aarnoud C. , Priestman David A. , Isacson Ole , Hallett Penelope J. , Platt Frances M. 
Published: November 2019

Abstract
Background
Haploinsufficiency in the Gaucher disease GBA gene, which encodes the lysosomal glucocerebrosidase GBA, and ageing represent major risk factors for developing Parkinson’s disease (PD). Recently, more than fifty other lysosomal storage disorder gene variants have been identified in PD, implicating lysosomal dysfunction more broadly as a key risk factor for PD. Despite the evidence of multiple lysosomal genetic risks, it remains unclear how sphingolipid hydrolase activities, other than GBA, are altered with ageing or in PD. Moreover, it is not fully known if levels of glycosphingolipid substrates for these enzymes change in vulnerable brain regions of PD. Finally, little is known about the levels of complex gangliosides in substantia nigra which may play a significant role in ageing and PD.

Methods
To study sphingolipid hydrolase activities and glycosphingolipid expression in ageing and in PD, two independent cohorts of human substantia nigra tissues were obtained. Fluorescent 4-methylumbelliferone assays were used to determine multiple enzyme activities. The lysosomal GBA and non-lysosomal GBA2 activities were distinguished using the inhibitor NB-DGJ. Sensitive and quantitative normal-phase HPLC was performed to study glycosphingolipid levels. In addition, glycosphingolipid levels in cerebrospinal fluid and serum were analysed as possible biomarkers for PD.

Results
The present study demonstrates, in two independent cohorts of human post-mortem substantia nigra, that sporadic PD is associated with deficiencies in multiple lysosomal hydrolases (e.g. α-galactosidase and β-hexosaminidase), in addition to reduced GBA and GBA2 activities and concomitant glycosphingolipid substrate accumulation. Furthermore, the data show significant reductions in levels of complex gangliosides (e.g. GM1a) in substantia nigra, CSF and serum in ageing, PD, and REM sleep behaviour disorder, which is a strong predictor of PD.

Conclusions
These findings conclusively demonstrate reductions in GBA activity in the parkinsonian midbrain, and for the first time, reductions in the activity of several other sphingolipid hydrolases. Furthermore, significant reductions were seen in complex gangliosides in PD and ageing. The diminished activities of these lysosomal hydrolases, the glycosphingolipid substrate accumulation, and the reduced levels of complex gangliosides are likely major contributors to the primary development of the pathology seen in PD and related disorders with age.
Ovarian endometrioma – a possible finding in adolescent girls and young women: a mini-review
Authors: Gałczyński Krzysztof , Jóźwik Maciej , Lewkowicz Dorota , Semczuk-Sikora Anna , Semczuk Andrzej 
Published: November 2019

Abstract
Young girls before menarche or menstruating adolescent women may experience long-term drug-resistant chronic pelvic pain, as well as other symptoms associated with pelvic mass. In such cases, it is of great importance to consider ovarian endometrioma in the differential diagnosis. In general, endometrioma is recognized as an ovarian cyst. However, in most cases, the pathology represents pseudocyst with a partial or complete endometrial-like lining with extraovarian adhesions and endometriotic implants which are likely to occur at the sites of ovarian adhesions and at the ceiling of the ovarian fossa. Ovarian endometriomas occur in 17–44% patients with endometriosis and account for 35% of all benign ovarian cysts. The time span from the onset of menarche to the time of endometrioma formation, which requires surgical intervention, has been evaluated to be a minimum of 4 years. The pathogenesis of early-life endometrioma may be different from other types of endometriosis. Diagnosis is often delayed, especially in adolescents, who tend to wait too long before seeking professional help. The three specific aims of treatment in adolescents with endometriosis and endometriomas are control of symptoms, prevention of further progression of the disease as well as preservation of fertility. Increasing evidence demonstrates association between ovarian endometriosis and ovarian cancer. In the present mini-review, we draw the particular attention of clinicians to such a possibility, even if relatively infrequently reported.
Imported cutaneous leishmaniasis: molecular investigation unveils Leishmania major in Bangladesh
Authors: Khan Md Anik Ashfaq , Chowdhury Rajashree , Nath Rupen , Hansen Sören , Nath Progga , Maruf Shomik , Abd El Wahed Ahmed , Mondal Dinesh 
Published: November 2019

Abstract

Background
The main clinical forms of leishmaniasis in Bangladesh are visceral leishmaniasis and post-kala-azar dermal leishmaniasis, which are caused by Leishmania donovani. Imported cutaneous leishmaniasis (CL) is emerging globally due mainly to increased human mobility. In recent years, several imported CL cases have also been reported in Bangladesh. Sporadic atypical cases of CL can be challenging for diagnosis and clinical management, while occurrence of infection on a frequent basis can be alarming. We report of a case of a Bangladeshi temporary-migrant worker who, upon return, presented development of skin lesions that are characteristic of CL.

Methods
A serum sample was collected and tested with an rK39 immunochromatographic test. Nucleic acid from skin biopsy derived culture sample was extracted and screened with a real-time PCR assay which targets the conserved REPL repeat region of L. donovani complex. The internal transcribed spacer 2 region of the ribosomal RNA gene cluster was amplified and sequenced.

Results
The suspect had a history of travel in both CL and VL endemic areas and had a positive rK39 test result. Based on clinical presentation, travel history and demonstration of the parasite in the skin biopsy, CL was diagnosed and the patient underwent a combination therapy with Miltefosine and liposomal amphotericin B. While typical endemic species were not detected, we identified Leishmania major, a species that, to our knowledge, has never been reported in Bangladesh.

Conclusions
Proper monitoring and reporting of imported cases should be given careful consideration for both clinical and epidemiological reasons. Molecular tests should be performed in diagnosis to avoid dilemma, and identification of causative species should be prioritized.
Two-weight norm inequalities for fractional integral operators with $A_{\lambda,\infty}$ weights
Authors: Pan Junren , Sun Wenchang 
Published: November 2019

AbstractIn this paper, we introduce a new class of weights, the$A_{\lambda, \infty}$Aλ,∞weights, which contains the classical$A_{\infty}$A∞weights. We prove a mixed$A_{p,q}$Ap,q–$A_{\lambda,\infty}$Aλ,∞type estimate for fractional integral operators.
Globally convergent method for designing twice spline contractual function
Authors: Zhu Zhichuan , Yao Yonghong , Postolache Mihai 
Published: November 2019

AbstractTo design a quadratic spline contractual function in the case of discretely unknown nodes, a modified constraint shifting homotopy algorithm for solving principal–agent problems is constructed in the paper. Then the existence of globally convergent solution to KKT systems for the principal–agent problem with spline contractual function is proved under a much weaker condition. The proposed algorithm only requires that any initial point is in the shifted feasible set but not necessarily in the original feasible set.
A contribution to knowledge on the terrestrial malacofauna of the Kastellorizo (Megisti) island group (SE Greece)
Authors: Mylonas Moisis , Vardinoyannis Katerina , Poulakakis Nikos 
Published: November 2019

Abstract

Background
The Kastellorizo island group (in the Dodecanese, Greece) is situated in the southeast corner of the Aegean Archipelago. It consists of twenty islets, of which the three largest (Kastellorizo, Ro and Strongyli) and seven smaller ones belong to Greece. Knowledge of the malacofauna on the islands is relatively poor. Only eight species were known prior to the present study, all from the islet of Kastellorizo.

Results
Here, using the scientific collections at the Natural History Museum of Crete collected mainly by the authors and also by several researchers since 1976, we reappraise the malacofauna of the island group. Thirty-one species were found in total (23 from Kastellorizo, 19 from Ro, 15 from Strongyli, 10 from Agios Georgios, 14 from Agrielia, 6 from Psomi and 10 from Psoradia).

Conclusions
The fact that there are no endemic snail species in the islands can be accounted for by their proximity to the Turkish coast, their common paleogeography with Turkey until the Late Pleistocene and Holocene, and the influence of humans. All but two species, Mastus etuberculatus and Vitrea riedeliana, are known from the adjacent Turkish coasts. Together with the subfossil species found on the smaller islets, the predominance of different species on each islet suggests a continuous substitution from the source areas of Turkey and the Aegean.