bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunotherapy for urothelial carcinoma: Metastatic disease and beyond
Authors: Poon Darren Ming‐Chun 
Published: August 2020

AbstractFor advanced and metastatic urothelial carcinomas (UCs), platinum (preferably cisplatin)‐based chemotherapy has been the standard treatment for many years. However, many patients are ineligible for cisplatin‐based chemotherapy because of poor performance status and/or other age‐related conditions. At the other end of the spectrum, patients with localized non‐muscle–invasive bladder cancer who are unresponsive to intravesical Bacillus Calmette‐Guérin (BCG) treatment often face radical cystectomy as the only option. In recent years, the application of immunotherapy in the form of immune‐checkpoint inhibitors has provided viable alternatives in the second‐line postplatinum and first‐line cisplatin‐ineligible settings. Recent and ongoing clinical trials are also assessing the safety and efficacy of immunotherapy for neoadjuvant and adjuvant uses before/after cystectomy, for BCG‐unresponsive cases, and for combination treatments that include the newer indoleamine 2,3‐dioxygenase‐1 inhibitors and/or BCG. This review summarizes recent developments in immunotherapy for UCs.
GC‐MS‐based metabolic signatures reveal comparative steroidogenic pathways between fetal and adult mouse testes
Authors: Han Soyun , Baba Takashi , Yanai Shogo , Byun Dong Jun , Morohashi Ken‐ichirou , Kim Jae‐Hong , Choi Man Ho 
Published: August 2020

AbstractBackgroundPrevious studies on gonadal steroidogenesis have not compared metabolic pathways between fetal and adult mouse testes to date.ObjectivesTo evaluate comparative metabolic signatures of testicular steroids between fetus and adult mice using gas chromatography‐mass spectrometry (GC‐MS)‐based steroid profiling.Materials and methodsGC‐MS with molecular‐specific scan modes was optimized for selective and sensitive detection of 23 androgens, 7 estrogens, 14 progestogens, and 13 corticoids from mouse testes with a quantification limit of 0.1‐5.0 ng/mL and reproducibility (coefficient of variation: 0.3%‐19.9%). Based on 26 steroids quantitatively detected in testes, comparative steroid signatures were analyzed for mouse testes of 8 fetuses on embryonic day 16.5 and 8 adults on postnatal days 56‐60.ResultsIn contrast to large amounts of steroids in adult testes (P < .0002), all testicular levels per weight unit of protein were significantly increased in fetal testes (P < .002, except 6β‐hydroxytestosterone of P = .065). Both 11β‐hydroxyandrostenedione and 7α‐hydroxytestosterone were only measurable in fetal testes, and metabolic ratios of testosterone to androstenediol and androstenedione were also increased in fetal testes (P < .05 for both).Discussion and conclusionTesticular steroid signatures showed that both steroidogenic Δ4 and Δ5 pathways in the production of testosterone were activated more during prenatal development. Both 7α‐ and 11β‐hydroxylations were predominant, while hydroxylations at C‐6, C‐15, and C‐16 of testosterone and androstenedione were decreased in the fetus. The present GC‐MS‐based steroid profiling may facilitate understanding of the development of testicular steroidogenesis.
Effects of cord milking in late preterm infants and full‐term infants: A systematic review and meta‐analysis
Authors: Ortiz‐Esquinas Inmaculada , Rodríguez‐Almagro Julián , Gómez‐Salgado Juan , Arias‐Arias Ángel , Ballesta‐Castillejos Ana , Hernández‐Martínez Antonio 
Published: August 2020

AbstractBackgroundUmbilical cord milking (UCM) consists of performing several milkings of the cord from the placenta to the newborn. The objective was to evaluate the effects of UCM on newborns ≥34 weeks’ gestation.MethodsSearches were conducted in MEDLINE, EMBASE, CINAHL, the Cochrane Database of Clinical Trials, and the clinicaltrails.gov database for randomized clinical trials (RCT), with no time or language restrictions, and for articles that compared UCM with other strategies. The main results were initial hemoglobin and hemoglobin after 6 weeks. The data were collected by two reviewers and the quality of the studies was assessed using the Cochrane Manual methodology.ResultsThe sample included 1845 newborns in 10 RCTs. The use of UCM in ≥34 weeks’ gestation newborns was not related to initial hemoglobin levels (pooled weighted mean difference: (PWMD = 0.40 g/L [−0.16 to 0.95]) or after 6 weeks (PWMD = 0.07 g/L [−0.29 to 0.27]). A reduction in hemoglobin levels was also observed at 6 weeks when the control group had undergone late clamping (PWDM = 0.16g/L [−0.26 to −0.06]).ConclusionsUCM produced no differences in hematologic variables for newborns with ≥34 weeks of gestation relative to controls. However, a slight decrease in hemoglobin levels is observed at 6 weeks when the control group is made up of newborns with late clamping.
Risk for lymph node metastasis in Epstein–Barr virus‐associated gastric carcinoma with submucosal invasion
Authors: Tsuji Yosuke , Ushiku Tetsuo , Shinozaki Tomohiro , Yamashita Hiroharu , Seto Yasuyuki , Fukayama Masashi , Fujishiro Mitsuhiro , Oda Ichiro , Katai Hitoshi , Taniguchi Hirokazu , Hasatani Kenkei , Kaizaki Yasuharu , Oga Atsunori , Nishikawa Jun , Akasaka Risaburo , Endo Masaki , Sugai Tamotsu , Matsumoto Takayuki , Koike Kazuhiko 
Published: August 2020

ObjectivesEpstein–Barr virus‐associated gastric cancer (EBVGC) has been reported to be associated with a low risk for lymph node metastasis (LNM). However, the curative criteria for endoscopic submucosal dissection (ESD) for submucosal EBVGC (pT1b‐EBVGC) remain unclear. Our study aimed to investigate the risk factors for LNM in pT1b‐EBVGC.MethodsThis was a retrospective multicenter study at five institutes in Japan. We reviewed medical records and extracted all pT1b‐EBVGC cases that met the following criteria: (i) histologically proven submucosal gastric cancer; (ii) surgical or endoscopic resection between January 2000 and December 2016; and (iii) presence of Epstein–Barr virus (EBV) in tumor cells verified by EBV‐encoded small RNA in situ hybridization (EBER‐ISH). The association between clinicopathological factors and LNM were assessed using multivariable logistic regression analysis.ResultsA total of 185 pT1b‐EBVGC cases were included in the analysis. LNM was found in nine cases (4.9%). Multivariable logistic regression analysis demonstrated that lymphatic invasion (OR 9.1; 95% CI 2.1–46.1) and submucosal invasion ≥4000 μm (OR 9.2; 95% CI 1.3–110.3) were significant risk factors for LNM. When we focused on pT1b‐EBVGC without lymphatic invasion and with submucosal invasion <2000 μm, the rate of LNM was 0% (0/96, 95% CI 0–3.8%).ConclusionsOur findings indicated that lymphatic invasion and submucosal invasion ≥4000 μm were significant risk factors for LNM. ESD could be an appropriate option for pT1b‐EBVGC without lymphatic invasion and with submucosal invasion <2000 μm.
Hydrocephalus due to marked enlargement of spinal roots in a patient with chronic inflammatory demyelinating polyradiculoneuropathy
Authors: Iwasaki A. , Kokubun N. , Funakoshi K. , Hirata K. , Suzuki K. 
Published: August 2020

BackgroundHydrocephalus or papilledema has rarely been reported in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).MethodsWe report a 65‐year‐old woman with a 12‐year history of CIDP presenting with progressive dementia, hallucination and deterioration of gait.ResultsNeurological examination revealed cognitive impairment, symmetric proximal and distal weakness with areflexia and muscle atrophy in the distal four limbs. The cerebrospinal fluid examination showed marked elevation of protein concentration. Magnetic resonance imaging revealed hydrocephalus and marked enlarged cervical and lumbar roots and plexus. The cervical cord and cauda equina were compressed by the swollen roots. A ventriculoperitoneal shunt resulted in reduction of the ventricles size along with improvement of her cognitive impairment.ConclusionIn our patient with CIDP, hydrocephalus was likely caused by hypertrophic nerve roots. Our findings suggest that CIDP patients with pronounced hypertrophic nerve roots require careful observation.
Bargaining power and outside options in the interbank lending market
Authors: Abbassi Puriya , Bräuning Falk , Schulze Niels 
Published: August 2020

AbstractWe study the role of bargaining power and outside options with respect to the pricing of over‐the‐counter interbank loans using a bilateral Nash bargaining model, and we test the model predictions with detailed transaction‐level data from the euro‐area interbank market. We find that lender banks with greater bargaining power over their borrowers charge higher interest rates, whereas the lack of alternative investment opportunities for lenders lowers bilateral interest rates. Moreover, we find that when lenders that are not eligible to earn interest on excess reserves (IOER) lend funds to borrowers with access to the IOER facility, they do so at rates that are below the IOER rate; in turn, these borrowers put the funds in their reserve accounts to earn the spread. Our findings highlight that this persistent arbitrage crucially depends on lenders’ limited bilateral bargaining power. We examine implications of these findings for the transmission of euro‐area monetary policy.
Sol‐gel assisted synthesis of TiB2‐B4C composite powder
Authors: GahremanDerakhshan Mahnaz , Nikzad Leila , Farvizi Mohammad , Ebadzadeh Touradj 
Published: August 2020

AbstractComposite powders containing titanium diboride and boron carbide have been prepared by sol‐gel method at 1450°C using titanium isopropoxide (titanium precursor), boric acid (Boron precursor), sucrose (carbon source), and acetic acid (AcOH) as a solvent. The effect of boron source (trimethyl borate and boric acid) and B2O3/TiO2, C/B2O3 mole ratios of starting materials on the final phases has been studied. The progress of reactions was determined using thermal analysis (TGA‐DTA). The resultant powders were characterized by X‐ray diffraction (XRD) analysis and field‐emission scanning electron microscope (FESEM). XRD patterns confirmed the formation of TiB2, B4C, and TiC phases after heat treatment at 1450°C at mole ratio of B2O3/TiO2 = 4.5, C/B2O3 = 2.4. With increasing the content of boron oxide, the unwanted phases such as TiC and C were reduced. TiB2 and B4C composite powders (~5 µm diameter) containing residual carbon (<4 wt%) were synthesized using the mole ratio of B2O3/TiO2 = 10 and C/B2O3 = 1.9 at low temperature of 1450°C.
ELECTROEJACULATION IN PATIENTS WITH SPINAL CORD INJURY: FIRST REPORT OF A LARGE‐SCALE EXPERIENCE FROM JAPAN
Authors: Momose Hitoshi , Hirao Yoshihiko , Yamamoto Masashi , Yamada Kaoru , Okajima Eigoro 
Published: August 2020

BackgroundEjaculatory dysfunction is a substantial obstacle for spinal cord‐injured men who have a desire to father their own children. Electroejaculation can potentially solve this problem. Recently, Halsted et al. reported outstanding results of the rectal probe electrostimulation (RPE) using newly developed equipment (Seager Model). In this paper, we report the first large‐scale clinical trial in Japan of RPE for spinal cord‐injured men.MethodsRPE using the Seager Model was attempted on 328 occasions in 53 patients with an age range of 19–47 years; 1–38 years had elapsed since injury.ResultsAntegrade ejaculation was obtained in 46 patients (86.8%). Ninety‐three percent of patients with upper motor neuron lesion‐type neurogenic bladder produced antegrade ejaculation by RPE, whereas the rate in patients with lower motor neuron lesion type one was 63.6% (P < 0.05). Semen analyses revealed affected sperm motility rate as low as 17.2%. Artificial insemination from these husbands (AIH) was attempted on 54 occasions in 11 wives of the patients. On April 2, 1992, we had the first recorded birth in Japan with the assistance of RPE and AIH. On July 21, 1993, we had another successful birth.ConclusionsThese promising results will encourage Japanese researchers to use electroejaculation, although the low success rate in patients with lower motor neuron lesion‐type neurogenic bladder and the low motility of the sperm are obstacles to be overcome.
A formalin inactivated whole SIVmac vaccine in Ribi adjuvant protects against homologous and heterologous SIV challenge
Authors: Putkonen Per , Thorstensson Rigmor , Cranage Martin , Nilsson Charlotta , Ghavamzadeh Lili , Albert Jan , Greenaway Peter , Biberfeld Gunnel 
Published: August 2020

Eight monkeys were immunized at 0, 4, 9, and 18 weeks with a total of 2 mg of formalin inactivated SIVmac vaccine with Ribi adjuvant. Two weeks after the last booster four immunized monkeys and two controls were challenged with 10 MID50 of live homologous virus SIVmac, and the remaining four vaccinated animals along with two controls were challenged with the heterologous SIVsm strain. All eight vaccinated monkeys resisted the virus challenge, whereas all controls became infected. Three months after the first challenge the monkeys were rechallenged with the same virus strain, without further boosting. Two of four vaccinated monkeys were still resistant to the homologous SIV strain, and three of four monkeys were resistant to the heterologous SIVsm strain. This study demonstrates vaccine induced cross‐protection between SIV strains.
An ultrasound study of the effect of chronic lead exposure on endometrial cycle changes in the female cynomolgus monkey
Authors: Foster Warren G. , Stals Sandra I. , McMahon Avril 
Published: August 2020

The effect of up to 10 years of lead (Pb) exposure (1500 μg/kg BW/day) on endometrial cycle changes in adult cynomolgus monkeys (n = 30) were examined by real‐time ultrasound. Pb exposure had no effect on peak serum estradiol (E2) or progesterone (P4) concentrations, menstrual cycle length, and endometrial response to gonadal steroids as determined by ultrasound.
Moderating effects of socio‐ecological factors on the relationship between adolescent exposure to media violence and attitudes towards school bullying
Authors: Moon Hee , Lee Seonah 
Published: August 2020

AbstractAimsTo examine the moderating effects of individual, family, and social factors on the relationship between adolescent exposure to media violence and attitudes towards school bullying.DesignA cross‐sectional study.MethodsA total of 473 middle and high school students participated in a self‐reported survey between August and October 2016. Self‐reported questionnaires were used to measure perceived aggression, resilience, parental violence experience, parenting styles, satisfaction with school life, teacher attitudes towards school bullying, media violence exposure, and adolescent attitudes towards school bullying. The data were analyzed using descriptive statistics and hierarchical multiple regression.ResultsResilience (an individual factor; β = −0.48, p = .049) and parenting styles (a family factor; β = −0.77, p = .045) moderated the negative influence of media violence exposure on adolescent attitudes towards school bullying. The findings indicated that higher individual resilience and parents with more positive parenting styles could reduce the harmful effects of media violence exposure on adolescent attitudes towards school bullying. The teachers’ attitudes towards school bullying (a school factor) contributed to predicting the adolescents’ attitudes towards school bullying. However, no moderating effect of school factors was found.ConclusionResilience and parenting styles are important socio‐ecological factors influencing the relationship between adolescent exposure to media violence and attitudes towards school bullying.ImpactThree types of intervention programmes can be suggested based on the results of this study. Reinforcing individual resilience and positive parenting styles should be considered important in developing intervention programmes targeted at eliminating the adverse effects of media violence exposure. Intervention programmes to develop parenting styles to increase the resilience of adolescents can also be considered. Lastly, programmes to screen for adverse outcomes of media violence exposure, low resilience, and poor parenting styles need to be developed.
Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signalling
Authors: Umar Meenakshi , Megarbane Andre , Shan Jingxuan , Syed Najeeb , Chouery Eliane , Aliyev Elbay , Jithesh Puthen , Temanni Ramzi , Mansour Issam , Chouchane Lotfi , Ismail Chouchane Aouatef 
Published: August 2020

AbstractFamilial Mediterranean fever (FMF) is the most common auto‐inflammatory disease. It is transmitted as autosomal recessive trait with mutations in MEditerranean FeVer (MEFV) gene. Despite a typical clinical expression, many patients have either a single or no mutation in MEFV. The current work is aimed to revisit the genetic landscape of FMF disease using high‐coverage whole genome sequencing. In atypical patients (carrying a single or no mutation in MEFV), we revealed many rare variants in genes associated with auto‐inflammatory disorders, and more interestingly, we discovered a novel variant ( a 2.1‐Kb deletion) in exon 11 of IL1RL1 gene, present only in patients. To validate and screen this patient‐specific variant, a tandem of allele‐specific PCR and quantitative real‐time PCR was performed in 184 FMF patients and 218 healthy controls and we demonstrated that the novel deletion was absent in controls and was present in more than 19% of patients. This study sheds more light on the mutational landscape of FMF. Our discovery of a disease‐specific variant in IL1RL1 gene may constitute a novel genetic marker for FMF. This finding suggesting a potential role of the IL33/ST2 signalling in the disease pathogenicity highlights a new paradigm in FMF pathophysiology.
Microwave pre‐treatment for vacuum drying of orange slices: Drying characteristics, rehydration capacity and quality properties
Authors: Özkan‐Karabacak Azime , Acoğlu Büşra , Yolci Ömeroğlu Perihan , Çopur Ömer U. 
Published: August 2020

AbstractMicrowave pre‐treatment for vacuum drying is a promising method in order to enhance heat and mass transfer rate. In this study, the influences of microwave pre‐treatment (90 W 30 min) on vacuum drying conducted at different combinations of drying temperature and absolute pressure (60, 70, and 80°C with 15 and 30 kPa) were investigated by evaluating the drying characteristics, rehydration capacity, and some quality attributes of orange slices. The vacuum drying treatments were carried out both with (MWVD) and without the microwave‐pretreatment (VD) at the same temperature and absolute pressure combinations. It was revealed that application of MWVD shortened the drying time of orange slices while increasing drying rate, effective moisture diffusivity and rehydration capacity. Six different semi‐theoretical mathematical models were applied, and Page, Modified Page, Logarithmic, and Lewis models were best fitted to experimental data of orange slices. It was observed that, among the different drying conditions applied in the scope of the study, VD at 80°C–15 kPa caused lowest color change (ΔE) that indicates the difference between the dried and fresh orange slices. All drying treatments caused a reduction in ascorbic acid content (AAC) (56.24–59.34%), total phenolic content (TPC) (15.92–55.79%) and total antioxidant capacity (TAC) (6.05–35.18%, 21.03–42.28%, and 54.76–69.07% for DPPH, FRAP, and CUPRAC assays, respectively) of orange slices. When MWVD and VD were compared, it was observed that MWVD caused less decrease in TPC and more in AAC and TAC. In conclusion, MWVD method is suggested as the more effective method providing lower drying time, faster drying rate, and better quality parameters of the product.Practical applicationsOrange including various nutrients with health beneficial effects is a perishable fruit. Therefore it is processed in to frozen, dried, canned, jam and fruit juice forms in order to increase its shelf life. Especially in seasons with overproduction, orange can be processed into dried form, and it can be turned into an alternative healthy snack with increased commercial value. In this research, drying characteristics of orange slices by microwave pre‐treated for vacuum drying were assessed with mathematical modeling. Drying conditions affected rehydration capacity, total phenolic content (TPC), total antioxidant capacity (TAC), ascorbic acid content (AAC) and color values of orange slices. Based on those outcomes, the optimum process conditions for an industrial drying application can be designed to enhance heat and mass transfer rate and to improve quality attributes of the product.
A low amyloidogenic E61K transthyretin mutation may cause familial amyloid polyneuropathy
Authors: Murakami Tatsufumi , Yokoyama Takeshi , Mizuguchi Mineyuki , Toné Shigenobu , Takaku Shizuka , Sango Kazunori , Nishimura Hirotake , Watabe Kazuhiko , Sunada Yoshihide 
Published: August 2020

AbstractPatients with transthyretin (TTR)‐type familial amyloid polyneuropathy (FAP) typically exhibit sensory dominant polyneuropathy and autonomic neuropathy. However, the molecular pathogenesis of the neuropathy remains unclear. In this study, we characterize the features of FAP TTR the substitution of lysine for glutamic acid at position 61 (E61K). This FAP was late‐onset, with sensory dominant polyneuropathy, autonomic neuropathy, and cardiac amyloidosis. Interestingly, no amyloid deposits were found in the endoneurium of the four nerve specimens examined. Therefore, we examined the amyloidogenic properties of E61K TTR in vitro. Recombinant wild‐type TTR, the substitution of methionine for valine at position 30 (V30M) TTR, and E61K TTR proteins were incubated at 37°C for 72 hr, and amyloid fibril formation was assessed using the thioflavin‐T binding assay. Amyloid fibril formation by E61K TTR was less than that by V30M TTR, and similar to that by wild‐type TTR. E61K TTR did not have an inhibitory effect on neurite outgrowth from adult rat dorsal root ganglion (DRG) neurons, but V30M TTR did. Furthermore, we studied the sural nerve of our patient by terminal deoxynucleotidyl transferase dUTP nick end labeling and electron microscopy. A number of apoptotic cells were observed in the endoneurium of the nerve by transferase dUTP nick end labeling. Chromatin condensation was confirmed in the nucleus of non‐myelinating Schwann cells by electron microscopy. These findings suggest that E61K TTR is low amyloidogenic, in vitro and in vivo. However, TTR aggregates and amyloid fibrils in the DRG may cause sensory impairments in FAP because the DRG has no blood–nerve barrier. Moreover, Schwann cell apoptosis may contribute to the neurodegeneration.
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