bluuebunny/crossref_metadata_2025_split huggingface dataset:
99mTc‐(EDDA/tricine)‐HYNIC‐GnRH analogue as a potential imaging probe for diagnosis of prostate cancer
Authors: Masteri Farahani Arezou , Maleki Fariba , Sadeghzadeh Nourollah , Abediankenari Saeid , Abedi Seyed Mohammad , Erfani Mostafa 
Published: April 2020

AbstractProstate cancer is a serious threat to men's health, so it is necessary to develop the techniques for early detection of this malignancy. Radiolabeled peptides are the useful tools for diagnosis of prostate cancer. In this research, we designed a new HYNIC‐conjugated GnRH analogue and labeled it by 99mTc with tricine/EDDA as coligands. We used aminohexanoic acid (Ahx) as a hydrocarbon linker to generate 99mTc‐(tricine/EDDA)‐HYNIC‐Ahx‐[DLys6]GnRH. The radiopeptide exhibited high radiochemical purity and stability in solution and serum. Two human prostate cancer cell lines LN‐CaP and DU‐145 were used for cellular experiments. The binding specificity and affinity of radiopeptide for LN‐CaP were superior to DU‐145 cells. The Kd values for LN‐CaP and DU‐145 cells were 41.91 ± 7.03 nM and 55.96 ± 10.56 nM, respectively. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor/muscle ratio of 99mTc‐HYNIC‐Ahx‐[DLys6]GnRH was 4.14 at 1 hr p.i. that decreased to 2.41 at 4 hr p.i. in LN‐CaP tumor‐xenografted nude mice. The blocking experiment revealed that the tumor uptake was receptor‐mediated. The lesion was visualized clearly using 99mTc‐[DLys6]GnRH at 1 hr p.i. Accordingly, this research highlights the capability of 99mTc‐(tricine/EDDA)‐HYNIC‐Ahx‐[DLys6]GnRH peptide as a promising agent for GnRHR‐expressing tumor imaging.
The effects of advanced maternal age on T-cell subsets at the maternal–fetal interface prior to term labor and in the offspring: a mouse study
Authors: Levenson D , Romero R , Garcia-Flores V , Miller D , Xu Y , Sahi A , Hassan S S , Gomez-Lopez N 
Published: April 2020

SummaryWomen who conceive at 35 years of age or older, commonly known as advanced maternal age, have a higher risk of facing parturition complications and their children have an increased risk of developing diseases later in life. However, the immunological mechanisms underlying these pathological processes have yet to be established. To fill this gap in knowledge, using a murine model and immunophenotyping, we determined the effect of advanced maternal age on the main cellular branch of adaptive immunity, T cells, at the maternal–fetal interface and in the offspring. We report that advanced maternal age impaired the process of labor at term, inducing dystocia and delaying the timing of delivery. Advanced maternal age diminished the number of specific proinflammatory T-cell subsets [T helper type 1 (Th1): CD4+IFN-γ+, CD8+IFN-γ+ and Th9: CD4+IL-9+], as well as CD4+ regulatory T cells (CD4+CD25+FoxP3+ T cells), at the maternal–fetal interface prior to term labor. Advanced maternal age also altered fetal growth and survival of the offspring in early life. In addition, infants born to advanced-age mothers had alterations in the T-cell repertoire but not in CD71+ erythroid cells (CD3−CD71+TER119+ cells). This study provides insight into the immune alterations observed at the maternal–fetal interface of advanced-age mothers and their offspring.
Weight gain after curative parathyroidectomy predicts increase in bone mineral density in patients with symptomatic primary hyperparathyroidism
Authors: Pal Rimesh , Arya Ashutosh K. , Aggarwal Anshita , Singh Priyanka , Dahiya Divya , Sood Ashwani , Singh Tulika , Ram Sant , Bhansali Anil , Bhadada Sanjay K. 
Published: April 2020

AbstractBackgroundPrimary hyperparathyroidism (PHPT) results in reduction of bone mineral density (BMD) and an increased risk of pathological fractures. Curative surgery does improve BMD; however, the magnitude of rise and predictive factors are highly variable amongst the hitherto available studies.ObjectivesTo quantify the magnitude of improvement in BMD after curative surgery in patients with symptomatic PHPT and dissect out the possible clinical and biochemical parameters predicting the BMD rise.MethodsWe conducted a retrospective study of symptomatic PHPT patients undergoing surgery between August 2016 and July 2018. Patients achieving biochemical cure with pre‐ and post‐operative (at least 1 year after surgery) dual‐energy X‐ray absorptiometry scans performed were included in the study.ResultsAfter exclusion, 63 patients were included in the study (M:F = 2:5; mean age = 44.8 years). At a median interval of 15 months, the median per cent change in BMD (ΔBMD) at lumbar spine (LS), total hip (TH), femoral neck (FN) and one‐third distal radius (forearm) was 6.5%, 7.0%, 8.1% and 6.9%, respectively. Following multiple linear regression analysis, baseline BMD was found to inversely predict ΔBMD at LS, TH and forearm. Pre‐operative iPTH positively predicted ΔBMD at LS and FN. Interestingly, 82.5% of the patients had a gain in body weight following curative surgery and change in body weight emerged as a significant positive predictor of ΔBMD at all sites.ConclusionsCurative surgery improves BMD at all sites in patients with symptomatic PHPT. Weight gain following surgery can be used as a positive clinical predictor of BMD rise.
Total keratometry in intraocular lens power calculations in eyes with previous laser refractive surgery
Authors: Lawless Michael , Jiang James Y. , Hodge Chris , Sutton Gerard , Roberts Timothy V. , Barrett Graham 
Published: April 2020

AbstractImportanceIntraocular lens (IOL) calculations in post‐refractive cases remain a concern. Our study identifies improved options for surgeons.BackgroundTo evaluate and compare the prediction accuracy of IOL power calculation methods after previous laser refractive surgery using standard keratometry (SK), measured posterior corneal astigmatism (PCA) and total keratometry (TK).DesignRetrospective consecutive cohort.ParticipantsA total of 50 consecutive patients (72 eyes) at a private institution who underwent cataract surgery with prior laser refractive procedures.MethodsMethods using SK included ASCRS mean, Barrett True‐K no history, Haigis‐L and Shammas IOL formulae. Barrett True‐K using posterior values (True K TK), Haigis and Holladay 1 Double‐K methods using TK were also assessed. Post‐surgery refraction was undertaken at minimum 3 weeks following surgery.Main Outcome MeasuresArithmetic and absolute IOL refractive prediction errors, variances in mean arithmetic IOL prediction error, and percentage of eyes within ±0.25D, ±0.50D, ±0.75D and ±1.00D of refractive prediction errors were compared.ResultsThe Barrett True‐K (TK) provided the lowest mean refractive prediction error (RPE) and variance for both prior myopes and hyperopes undergoing cataract surgery. The Barrett True‐K (TK) exhibited the highest percentages of eyes within ±0.50D, ±0.75D and ±1.00D of the RPE compared to other formulae for prior myopic patients.Conclusions and RelevanceAccuracy of IOL power calculations in post‐laser eyes can be improved by the addition of posterior corneal values as measured by the IOLMaster 700. The use of total keratometry may supplement outcomes when no prior refraction history is known.
Comprehensive molecular analysis of 61 Egyptian families with hereditary nonsyndromic hearing loss
Authors: Budde Birgit S. , Aly Maha Abdelgaber , Mohamed Mostafa R. , Breß Andreas , Altmüller Janine , Motameny Susanne , Kawalia Amit , Thiele Holger , Konrad Kathryn , Becker Christian , Toliat Mohammad R. , Nürnberg Gudrun , Sayed Eman Abdel Fattah , Mohamed Enass Sayed , Pfister Markus , Nürnberg Peter 
Published: April 2020

AbstractNonsyndromic hearing loss is an extremely heterogeneous disorder. Thus, clinical diagnostics is challenging, in particular due to differences in the etiology of hearing loss between populations. With this study, we wanted to elucidate the genetic basis of hearing loss in 61 consanguineous Egyptian families. In 25 families, linkage analysis was used as a prescreening to identify regions for targeted sequencing of candidate genes. Initially, the coding regions of 12 and later of 94 genes associated with hearing loss were enriched and subjected to massively parallel sequencing (MPS) with diagnostic yields of 36% and 75%, respectively. Causative variants were identified in 48 families (79%). They were found in 23 different genes with the majority being located in MYO15A (15.3%), SLC26A4 (9.7%), GJB2 (8.3%), and MYO7A (6.4%). As many as 32 variants were novel ones at the time of detection. Five variants were shared by two, three, or even four families. Our study provides a first survey of the mutational spectrum of deaf patients in Egypt revealing less GJB2 variants than in many European populations. It underlines the value of targeted enrichment of well‐selected deafness genes in combination with MPS in the diagnostics of this frequent and genetically heterogeneous disorder.
Further delineation of the female phenotype with KDM5C disease causing variants: 19 new individuals and review of the literature
Authors: Carmignac Virginie , Nambot Sophie , Lehalle Daphné , Callier Patrick , Moortgat Stephanie , Benoit Valérie , Ghoumid Jamal , Delobel Bruno , Smol Thomas , Thuillier Caroline , Zordan Cécile , Naudion Sophie , Bienvenu Thierry , Touraine Renaud , Ramond Francis , Zweier Christiane , Reis André , Kraus Cornelia , Nizon Mathilde , Cogné Benjamin , Verloes Alain , Tran Mau‐Them Frédéric , Sorlin Arthur , Jouan Thibaud , Duffourd Yannis , Tisserant Emilie , Philippe Christophe , Vitobello Antonio , Thevenon Julien , Faivre Laurence , Thauvin‐Robinet Christel 
Published: April 2020

AbstractX‐linked intellectual disability (XLID) is a genetically heterogeneous condition involving more than 100 genes. To date, 35 pathogenic variants have been reported in the lysine specific demethylase 5C (KDM5C) gene. KDM5C variants are one of the major causes of moderate to severe XLID. Affected males present with short stature, distinctive facial features, behavioral disorders, epilepsy, and spasticity. For most of these variants, related female carriers have been reported, but phenotypic descriptions were poor. Here, we present clinical and molecular features of 19 females carrying 10 novel heterozygous variants affecting KDM5C function, including five probands with de novo variants. Four heterozygous females were asymptomatic. All affected individuals presented with learning disabilities or ID (mostly moderate), and four also had a language impairment mainly affecting expression. Behavioral disturbances were frequent, and endocrine disorders were more frequent in females. In conclusion, our findings provide evidence of the role of KDM5C in ID in females highlighting the increasing implication of XLID genes in females, even in sporadic affected individuals. Disease expression of XLID in females should be taken into consideration for genetic counseling.
Tibolone, alendronate, and simvastatin enhance implant osseointegration in a preclinical in vivo model
Authors: Apostu Dragos , Lucaciu Ondine , Mester Alexandru , Oltean‐Dan Daniel , Gheban Dan , Rares Ciprian Benea Horea 
Published: April 2020

AbstractObjectivesThe objective of the study was to evaluate and compare the effect of different drugs such as simvastatin, alendronate, and tibolone for titanium implant osseointegration enhancement.Materials and methodsEighty female albino Wistar rats were equally divided into five groups: Group I (ovariectomy), Group II (sham ovariectomy), Group III (alendronate + ovariectomy), Group IV (simvastatin + ovariectomy), and Group V (tibolone + ovariectomy). Three months after ovariectomy, we performed bilateral titanium intramedullary nailing in all groups, followed by oral administration of alendronate, simvastatin, or tibolone for 12 weeks. Examinations included micro‐CT, mechanical pull‐out test, histology, and bone serum markers.ResultsPeri‐implant micro‐CT analysis showed a significantly higher overall bone tissue in tibolone compared to the ovariectomy group, while no significant difference was found between the treatment groups. Sham ovariectomy, alendronate, and tibolone groups had a higher body mass density compared to ovariectomy and simvastatin groups. All treatment groups had a greater thickness of the peri‐implant compact bone layer compared to ovariectomy group, but the results were not statistically significant. Tibolone presented the highest values in pull‐out test, but alendronate showed more consistently positive results compared to other groups. Osteocalcin had in the tibolone group almost three times the value in the ovariectomy group, but the results were not statistically significant.ConclusionThe hypothesis that alendronate, simvastatin, and tibolone enhance the osseointegration process of intramedullary titanium implants in ovariectomized rats has been accepted, while tibolone could offer the best results.
PD‐L1 and LAG‐3 expression in advanced cutaneous squamous cell carcinomas
Authors: Wu Sam , Slater Nathaniel A. , Sayed Christopher J. , Googe Paul B. 
Published: April 2020

AbstractBackgroundExpression of programmed death ligand 1 (PD‐L1) by cutaneous squamous cell carcinomas has been shown to correlate with advanced disease and risk of metastasis. Lymphocyte activation gene 3 (LAG‐3, or CD223) is an inhibitory receptor that interacts with the PD‐L1 axis, which has been shown to be a marker of immune exhaustion and a potential immunotherapy target. However, the role of LAG‐3 in cutaneous squamous cell carcinoma has not been established.MethodsWe reviewed 18 cases of locally advanced and/or metastatic cutaneous squamous cell carcinomas and assessed for PD‐L1 expression, presence or absence of tumor‐infiltrating lymphocytes (TILs), and expression of LAG‐3 by TILs.ResultsPD‐L1 expression was present in 11 of 13 locally advanced primary tumors and 5 of 5 metastases. TILs were present in all 18 tumors, of which 14 cases were positive for LAG‐3 expression. In positive cases, LAG‐3 was expressed on average by 32% of TILs.ConclusionsAdvanced cutaneous squamous cell carcinomas frequently express PD‐L1 and are associated with an inflammatory response. LAG‐3 expression by TILs was identified in a majority of cases. Our findings suggest that LAG‐3 positive tumor‐associated inflammatory cells may play a role in the development of advanced disease and offer another potential target for drug therapy.
Combining geostatistical and biotic interaction model to predict amphibian refuges under crayfish invasion across dendritic stream networks
Authors: Mota‐Ferreira Mário , Beja Pedro 
Published: April 2020

AbstractAimBiological invasions are pervasive in freshwater ecosystems, often causing native species to contract into areas that remain largely free from invasive species impacts. Predicting the location of such ecological refuges is challenging, because they are shaped by the habitat requirements of native and invasive species, their biotic interactions, and the spatial and temporal invasion patterns. Here, we investigated the spatial distribution and environmental drivers of refuges from invasion in river systems, by considering biotic interactions in geostatistical models accounting for stream network topology. We focused on Mediterranean amphibians negatively impacted by the invasive crayfishes Procambarus clarkii and Pacifastacus leniusculus.LocationRiver Sabor, NE Portugal.MethodsWe surveyed amphibians at 168 200‐m stream stretches in 2015. Geostatistical models were used to relate the probabilities of occurrence of each species to environmental and biotic variables, while controlling for linear (Euclidean) and hydrologic spatial dependencies. Biotic interactions were specified using crayfish probabilities of occurrence extracted from previously developed geostatistical models. Models were used to map the distribution of potential refuges for the most common amphibian species, under current conditions and future scenarios of crayfish expansion.ResultsGeostatistical models were produced for eight out of 10 species detected, of which five species were associated with lower stream orders and only one species with higher stream orders. Six species showed negative responses to one or both crayfish species, even after accounting for environmental effects and spatial dependencies. Most amphibian species were found to retain large expanses of potential habitat in stream headwaters, but current refuges will likely contract under plausible scenarios of crayfish expansion.Main conclusionsIncorporating biotic interactions in geostatistical modelling provides a practical and relatively simple approach to predict present and future distributions of refuges from biological invasion in stream networks. Using this approach, our study shows that stream headwaters are key amphibian refuges under invasion by alien crayfish.
Emerging evidence for cell‐autonomous axon guidance
Authors: Harada Hidekiyo , Charish Jason , Monnier Philippe P. 
Published: April 2020

AbstractCurrent models of axon guidance within the central nervous system (CNS) involve the presentation of environmental cues to navigating growth cones. The surrounding and target tissues present a variety of ligands that either restrict or promote growth, thus providing pathfinding instructions to developing axons. Recent findings show that RGMb, a GPI anchored extracellular protein present on retinal ganglion cells, down‐regulates Wnt3a signaling by lowering LRP5 levels at the membrane surface. When RGMb is phosphorylated by the extracellular tyrosine kinase VLK, phosphorylated RGMb (p‐RGMb) is internalized and carries LRP5 towards intracellular compartments. In the eye, a dorsal‐high ventral‐low gradient of VLK generates a dorsal‐low ventral‐high gradient of LRP5 that modulates Wnt3a signaling. These molecules, which are all expressed by individual RGCs, generate Wnt‐signal gradients along the dorso‐ventral axis of the retina, resulting in differential axon growth which in turn regulates proper retino‐tectal/collicular map formation. This pathway represents a regulatory mechanism whereby extracellular phosphorylation generates what may be the first example of a unique self‐guiding mechanism that affects neuronal‐target connections independent of paracrine signals from the surrounding target tissue.
Prevalence of pyruvate kinase deficiency: A systematic literature review
Authors: Secrest Matthew H. , Storm Mike , Carrington Courtney , Casso Deborah , Gilroy Keely , Pladson Leanne , Boscoe Audra N. 
Published: April 2020

AbstractObjectivesPyruvate kinase deficiency (PK deficiency) is a rare disorder caused by compound heterozygosity or homozygosity for > 300 mutations in the PKLR gene. To understand PK deficiency prevalence, we conducted a systematic literature review.MethodsWe queried Embase and Medline for peer‐reviewed references reporting PK deficiency prevalence/incidence, PKLR mutant allele frequency (MAF) among the general population, or crude results from which these metrics could be derived.ResultsOf 1390 references screened, 1296 were excluded after title/abstract review; 60 were excluded after full‐text review. Four of the remaining 34 studies were considered high‐quality for estimating PK deficiency prevalence. Two high‐quality studies identified cases from source populations of known sizes, producing estimates of diagnosed PK deficiency prevalence of 3.2 and 8.5 per million. Another high‐quality study derived an estimate of diagnosed PK deficiency prevalence of 6.5 per million by screening jaundiced newborns. The final high‐quality study estimated total diagnosed and undiagnosed PK deficiency prevalence to be 51 per million through extrapolation from observed MAFs.ConclusionsWe conclude that prevalence of clinically diagnosed PK deficiency is likely between 3.2 and 8.5 per million in Western populations, while the prevalence of diagnosed and undiagnosed PK deficiency could possibly be as high as 51 per million.
Automatic Holter electrocardiogram analysis in ischaemic stroke patients to detect paroxysmal atrial fibrillation: ready to replace physicians?
Authors: Gröschel S. , Lange B. , Grond M. , Jauss M. , Kirchhof P. , Rostock T. , Wachter R. , Gröschel K. , Uphaus T. 
Published: April 2020

Background and purposeThe detection of paroxysmal atrial fibrillation (pAF) in patients presenting with ischaemic stroke shifts secondary stroke prevention to oral anticoagulation. In order to deal with the time‐ and resource‐consuming manual analysis of prolonged electrocardiogram (ECG)‐monitoring data, we investigated the effectiveness of pAF detection with an automated algorithm (AA) in comparison to a manual analysis with software support within the IDEAS study [study analysis (SA)].MethodsWe used the dataset of the prospective IDEAS cohort of patients with acute ischaemic stroke/transient ischaemic attack presenting in sinus rhythm undergoing prolonged 72‐h Holter ECG with central adjudication of atrial fibrillation (AF). This adjudicated diagnosis of AF was compared with a commercially available AA. Discordant results with respect to the diagnosis of pAF were resolved by an additional cardiological reference confirmation.ResultsParoxysmal AF was finally diagnosed in 62 patients (5.9%) in the cohort (n = 1043). AA more often diagnosed pAF (n = 60, 5.8%) as compared with SA (n = 47, 4.5%). Due to a high sensitivity (96.8%) and negative predictive value (99.8%), AA was able to identify patients without pAF, whereas abnormal findings in AA required manual review (specificity 96%; positive predictive value 60.6%). SA exhibited a lower sensitivity (75.8%) and negative predictive value (98.5%), and showed a specificity and positive predictive value of 100%. Agreement between the two methods classified by kappa coefficient was moderate (0.591).ConclusionAutomated determination of ‘absence of pAF’ could be used to reduce the manual review workload associated with review of prolonged Holter ECG recordings.
Estimating the potential for coral adaptation to global warming across the Indo‐West Pacific
Authors: Matz Mikhail V. , Treml Eric A. , Haller Benjamin C. 
Published: April 2020

AbstractThe potential of reef‐building corals to adapt to increasing sea‐surface temperatures is often debated but has rarely been comprehensively modeled on a region‐wide scale. We used individual‐based simulations to model adaptation to warming in a coral metapopulation comprising 680 reefs and representing the whole of the Central Indo‐West Pacific. Encouragingly, some reefs—most notably Vietnam, Japan, Taiwan, New Caledonia and the southern half of the Great Barrier Reef—exhibited high capacity for adaptation and, in our model, maintained coral cover even under a rapid “business‐as‐usual” warming scenario throughout the modeled period (200 years). Higher resilience of these reefs was observed under all tested parameter settings except the models prohibiting selection and/or migration during warming. At the same time, the majority of reefs in the region tended to collapse within the first 100 years of warming. The adaptive potential (odds of maintaining high coral cover) of a given reef could be predicted based on two metrics: the reef's present‐day temperature, and the proportion of recruits immigrating from warmer locations. The latter metric explains the most variation in adaptive potential, and significantly correlates with actual coral cover changes observed throughout the region between the 1970s and the early 2000s. These findings will help prioritize coral conservation efforts and plan assisted gene flow interventions to boost the adaptive potential of specific coral populations.