bluuebunny/crossref_metadata_2025 huggingface dataset:
Normothermic extracorporeal membrane oxygenation support: Improving the function of intestinal grafts obtained from cardiac death donors
Authors: Guo Mingxiao , Lu Chunlei , Li Linlin , Yao Danhua , Li Yousheng
Published: April 2020

Extracorporeal membrane oxygenation (ECMO) could ameliorate the energy status and viability of bowel grafts from cardiac death donors. However, the function of these grafts after transplantation is not clear. The purpose of the study was to evaluate the early function of intestinal grafts after transplantation from expected cardiac death donors supported with normothermic extracorporeal support using a porcine allogeneic orthotopic segmental small bowel transplantation model. Eighteen domestic crossbred donor pigs were assigned to living donation (LD), donation after cardiac death (DCD), and ECMO groups. In the LD group, small bowels were harvested and preserved immediately in cold storage. In the other two groups, the donor pigs received conventional rapid recovery treatment or 1‐hour normothermic extracorporeal support after 10‐minutes expected cardiac arrest. Subsequently, the small bowels were removed and preserved in cold storage. After 5‐6 hours of preservation, small bowel grafts were transplanted into the recipient pigs that underwent enterectomy. The pathology and electron microscopy results, cell apoptosis rate, tight junction protein expression level in the intestinal mucosa, and plasma endotoxin level were evaluated after transplantation. All grafts functioned on the basis of the maltose absorption test results at day 7 after transplantation. There were no significant differences in the morphological changes in the intestinal mucosa among the three groups at day 7 after transplantation. The cell apoptosis rate and plasma endotoxin level in the ECMO group did not differ significantly than those in the LD group, but were evidently lower than those in the DCD group (P < .001). The intestinal absorptive function improved significantly in the ECMO group in contrast with that in the DCD group (P < .001). Short‐term ECMO intervention can alleviate ischemia–reperfusion injuries in intestinal grafts and improve intestinal absorptive function in the early stage after transplantation. Reducing caspase‐3 protein expression and cell apoptosis in the intestinal mucosa may be one of the protective mechanisms of ECMO intervention.
Acute stunning effect of hemodialysis on myocardial performance: A three‐dimensional speckle tracking echocardiographic study
Authors: Guler Hasan Selim , Tulunay Kaya Cansin , Kumru Gizem , Kosku Hakan , Ozyuncu Nil , Sengul Sule , Kutlay Sim
Published: April 2020

The effects of acute changes during hemodialysis (HD) on the myocardium are not yet known. The invention of three‐dimensional speckle tracking echocardiography (3DSTE) has offered clinicians a new method to assess the movements of ventricular segments simultaneously in three spatial directions. The aim of this study was to evaluate the effect of first weekly standard HD process on the left ventricle (LV) and right ventricle (RV) global and regional myocardial function in patients with normal left ventricle ejection fraction using 3DSTE‐derived indices. Patients (n=38) receiving maintenance HD in our clinic who have no known cardiovascular disease are examined just before and after a HD session using 3DSTE. Demographic and comorbidity data, renal replacement treatment characteristics, and laboratory test results are recorded. 3DSTE analysis is performed to calculate the LV global longitudinal, circumferential area and radial peak systolic strain, as well as RV septum and free‐wall longitudinal strain and fractional area change. Patients are aged 52.8 ± 13.6 years and 52.6% of them are male. Mean dialysis duration is 56 months. The LV strain values of the patients changed markedly before and after HD (GLS: −14.2 ± 5.2, −11.1 ± 4.6 [P < .001], GCS: −14.8 ± 4.2, −12.4 ± 5.28 [P < .009]; GRS: 41.5 ± 16, 33.3 ± 16.5 [P = .003]; AREA −24.7 ± 7.2, −20.1 ± 7.6 [P = .001], respectively). We could not demonstrate any improvement in RV strain values before or after HD. LV strain values are positively correlated with blood pressure variability during the dialysis sessions. LV function is preserved better after HD in patients on beta or calcium channel blocker therapy compared to those who do not use these agents (P < .001, P < .01, respectively). HD treatment results in deterioration in all LV strain directions but not in RV. Strain assessment may improve vascular risk stratification of patients on chronic HD.
Determining factors for hemodiafiltration to equal or exceed the performance of expanded hemodialysis
Authors: Maduell Francisco , Broseta José Jesús , Gómez Miguel , Racionero Pablo , Montagud‐Marrahi Enrique , Rodas Lida , Arias‐Guillén Marta , Fontseré Néstor , Vera Manel , Rico Nayra
Published: April 2020

The aim of the study was to compare expanded hemodialysis (HDx) with hemodiafiltration (HDF) at different infusion flows to identify the main determinants, namely blood flow (Qb), replacement volume, infusion flow (Qi), ultrafiltration flow (Quf), filtration fraction (FF), and the point at which the effectiveness of HDF equals or exceeds that of HDx. We conducted a prospective, single‐center study in 12 patients. Each patient underwent 12 dialysis sessions: six sessions with Qb 350 and six with Qb 400 mL/min; with each Qb, one session was with HDx and five sessions were with FX80 (one in HD, and four with Qi 50, 75, 90/100 mL/min or autosubstitution in postdilution HDF). The reduction ratios (RR) of urea, creatinine, ß2‐microglobulin, myoglobin, prolactin, α1‐microglobulin, α1‐acid glycoprotein, and albumin were compared intraindividually and the global removal score (GRS) was calculated. The mean replacement volume with Qb 350 mL/min was 13.77 ± 0.92 L with Qi 50 mL/min, 20.75 ± 1.17 L with Qi 75, 23.83 ± 1.92 L with Qi 90, and 27.51 ± 2.77 L with autosubstitution. Similar results were obtained with Qb 400 mL/min, and the results were only slightly higher with Qi 100 mL/min or in autosubstitution. The GRS was positively correlated with replacement volume with Qb 350 (R2 = 0.583) and with Qb 400 (R2 = 0.584); with Quf with Qb 350 (R2 = 0.556) and with Qb 400 (R2 = 0.604); and also with FF with Qb 350 (R2 = 0.556) and with Qb 400 mL/min (R2 = 0.603). The minimum convective volume in HDF from which it is possible to overcome the efficacy of HDx was 19.2 L with Qb 350 and 17.6 L with Qb 400 mL/min. The cut‐off point of Quf at which HDF exceeded the effectiveness of HDx was 80.6 mL/min with Qb 350 and 74.1 mL/min with Qb 400 mL/min. The cut‐off point at which FF in HDF exceeded the effectiveness of the HDx was 23.0% with Qb 350 and 18.6% with Qb 400 mL/min. In conclusion, this study confirms the superiority of postdilution HDF over HDx when replacement volume, convective volume, Quf, or FF exceeds certain values. Increasing the Qb in postdilution HDF manages to increase the convective dose and more easily overcome the HDx.
Decellularized scaffolds for tissue engineering: Current status and future perspective
Authors: Rajab Taufiek Konrad , O’Malley Thomas J. , Tchantchaleishvili Vakhtang
Published: April 2020

Based on Organ Procurement and Transplantation Network data as of December 2019, more than 113 000 patients require an organ transplantation, yet, over the course of this past year, only 36 000 patients received a transplant. This discrepancy between those that need a donor organ and those that receive one remains one of medicine’s biggest challenges. Multiple solutions, both biologic and artificial, have been proposed to mitigate this difference. One of the most promising approaches to generate bioartificial organs for transplantation involves re‐seeding decellularized scaffolds with appropriate cells. Decellularization involves physical, chemical, or biological methods that typically require intimate contact of various decellularization solutions with each cell. Consequently, conventional submersion decellularization has been limited to simple tissues such as heart valves. The invention of perfusion decellularization was a breakthrough that allowed the generation of tissue‐engineered scaffolds from tissues with higher structural organization and entire organs. Such scaffolds are composed of a myriad of extracellular matrix (ECM) components that include collagen, elastin, proteoglycans, and glycoproteins. Together, these components allow the scaffolds to fulfill specialized functions, such as structural functions as well as biological functions including the regulation of cellular processes and extracellular molecules. These specialized functions of decellularized scaffolds can increasingly be harnessed for applications in tissue engineering.
A case series of patients with left ventricular assist devices and concomitant mechanical heart valves
Authors: Al Saadi Tareq , Andrade Ambar , Chickerillo Krystina , Joshi Anjali , Sciamanna Christopher , Pauwaa Sunil , Macaluso Gregory , Dia Muhyaldeen , Cotts William , Tatooles Antone , Pappas Patroklos
Published: April 2020

Mechanical heart valves left in situ at the time of left ventricular assist device (LVAD) implantation are thought to potentially increase the risk of thromboembolism. Recommendations exist to replace dysfunctional mechanical mitral valves and any mechanical aortic valves at the time of LVAD implantation. Due to potential increases in cardiopulmonary bypass time and associated comorbidities with valve replacement, leaving a functional mechanical valve in place at LVAD implantation has been suggested to be a safe option. We retrospectively reviewed all patients with prior mechanical mitral or aortic valves undergoing LVAD implantation at our center between 2012 and 2017. Echocardiograms were read by a single cardiologist to assess for mechanical valve dysfunction. We identified 15 patients. Five patients had major bleeding requiring transfusion. On follow‐up, 2 patients had hemorrhagic stroke and 2 had transient ischemic attach/ischemic stroke. In addition, 2 patients had LVAD thrombosis and 2 patients had LVAD driveline malfunction. Mild mechanical valve regurgitation was identified on follow‐up echocardiograms of 2 patients. Rate of complications in patients with mechanical valves undergoing LVAD implantation was comparable to that reported for the general LVAD population. Leaving a functional mechanical valve in place at the time of LVAD implantation could be a reasonable alternative to valve replacement. More data are required to further guide patient care in these individuals.
High recurrence rate in patients with choroidal hemangioma treated with limited single spot photodynamic therapy during long‐term follow‐up
Authors: Stehouwer Marilette , Schlingemann Reinier O. , Verbraak Frank D.
Published: April 2020

Purpose

To evaluate the long‐term follow‐up of patients with a circumscribed choroidal hemangioma (CCH) treated with limited single spot photodynamic therapy (PDT) at the Amsterdam University Medical Center, location AMC (AUMC).

Methods

This cross‐sectional study included 17 patients, treated between 2001 and 2012. Evaluation included best corrected visual acuity, slitlamp examination, fundoscopy, ophthalmic ultrasonography (USG), fluorescein/indocyanine green angiography (FA/ICG), fundus autofluorescence (FAF) and optical coherence tomography (OCT). Primary outcome: recurrence rate, secondary outcomes: long‐term functional and structural changes.

Results

An unexpected high recurrence rate of 35% (n6) was found with a mean follow‐up time between treatment and recurrence of almost 6 years, range 2.8–10.7 years. With a recurrence, the classical CCH pattern was no longer recognizable on FA or ICG. Signs of leakage were best observed with OCT, and the recurrence could be confirmed with USG. Retreatment with PDT of all recurrences was successful. After a successful initial PDT, the achieved visual acuity (VA) showed a small decrease over time, median VA from 0.10 LogMar to 0.15 LogMar (p 0.09) after a mean follow‐up of 11.36 years (range 5.1–15.5 years). During follow‐up study visit, the OCT revealed a slightly increased thickness of the choroid in 86% of cases at the site of the original tumour, without a clear correlation to the recurrences.

Conclusion

Limited single spot PDT is a safe and effective treatment for CCH preserving a good VA. However, because of the relatively high recurrence rate found in this study, we recommend regular follow‐up with OCT every 6 months.
Perioperative risk of bleeding with antithrombotic agents in macular surgery: a national, prospective, multicentre study
Authors: Louison Solenne , Gabrielle Pierre‐Henry , Soudry Agnès , Meillon Cyril , Blanc Julie , Béal Guillaume , Arsène Sophie , Le Mer Yannick , Berrod Jean‐Paul , Kodjikian Laurent , Creuzot‐Garcher Catherine ,   for the CFCR Research net
Published: April 2020

Purpose

To compare the risk of haemorrhagic complications in elective macular surgery between patients with no antithrombotic (AT) treatment (defined as patients with no history of AT therapy or who discontinued AT therapy) and patients who continued AT treatment during the surgery.

Methods

E‐case report forms were prospectively recorded in a database before vitreoretinal surgery and 1 month after. Data on patient characteristics, surgical techniques, haemorrhagic complications and antithrombotic status were collected. Patients with retinal detachment, proliferative diabetic retinopathy and previous retinal haemorrhage were excluded.

Results

A total of 748 procedures (single procedure in one eye per patient) were performed between January and May 2019. Among them, 202 patients (27.0%) were treated with antithrombotic therapy at the time of surgery: 19.5% with antiplatelet agents (n = 146), 6.3% with anticoagulants (n = 47) including 3.2% (n = 24) patients treated with novel oral anticoagulants, 0.8% (n = 6) with anticoagulants and antiplatelet agents, and 0.4% (n = 3) with heparin. Overall, 92 patients (12.3%) developed one or more haemorrhagic complications, of which 63 (11.5%) and 29 (14.4%) were in the non‐AT and AT group, respectively. The multivariate logistic regression model showed no difference between AT treatment groups regarding ocular bleeding complications (odds ratio [OR] 1.2, 95% confidence interval (CI) [0.7–2.2], p = 0.54).

Conclusion

No cases of uncontrolled or severe perioperative haemorrhage in patients continuing antithrombotic agents were reported in this selected population. For the majority of the patients taking antiplatelets or anticoagulants, these agents could be safely continued during macular surgery.
Is Work Engagement Exhausting? The Longitudinal Relationship Between Work Engagement and Exhaustion Using Latent Growth Modeling
Authors: Junker Nina M. , Kaluza Antonia J. , Häusser Jan A. , Mojzisch Andreas , van Dick Rolf , Knoll Michael , Demerouti Evangelia
Published: April 2020

The relationship between exhaustion and work engagement has received considerable attention during the past decades. Although the theoretical proposition exists that work engagement may increase exhaustion over time, previous research has been mixed. Drawing on the transactional stress model and applying latent growth modeling, we aim to provide a more comprehensive picture of the work engagement–exhaustion relationship over time. In two longitudinal studies, with four measurement points each, we found consistent evidence that a higher initial work engagement related to increased exhaustion over time. Consistent with our hypotheses, a higher initial work engagement also related to less initial exhaustion, and increases in work engagement related to decreases in exhaustion over time. However, contrary to our expectations, a higher initial exhaustion related to elevated work engagement over time. In conclusion, our findings suggest that engaged employees are less exhausted but face a higher risk of exhaustion over time. At the same time, exhausted employees are less engaged, but they have the potential to become more so over time. The theoretical and practical implications of these findings will be discussed in this paper.
Letter: Covid‐19, and vitamin D. Authors' reply
Authors: Tian Yuan , Rong Long
Published: April 2020

LINKED CONTENT

This article is linked to Sands et al papers. To view these articles, visit https://doi.org/10.1111/apt.15555 and https://doi.org/10.1111/apt.15716.
The network approach to assess the structure of knowledge: Storage, distribution and retrieval as three measures in analysing concept maps
Authors: Kapuza Anastasiya , Koponen Ismo T. , Tyumeneva Yulia
Published: April 2020

We present three new standardised network concept map (CM) measures that can provide unique information about learning‐related progress, which cannot be determined from previously known measures. Grounded in cognitive development theory on the one hand, and network theory on the other hand, our measures reveal how knowledge is stored, distributed and retrieved. We validated the new measures by testing their ability to discriminate between CMs of respondents with different levels of competency in statistics (students before and after taking an introductory statistics course and experts in the field of statistics). We also validated our measures against the most commonly used traditional and network measures. Based on a small sample of respondents, we show that two of the newly proposed compound measures reveal significant differences between experts and novices in the field, with higher values for experts, showing that expert knowledge is better distributed, more connected and balanced. More importantly, our measures were sensitive enough to show learning‐related progress for students, albeit statistically non‐significant, while common indicators from network theory did not demonstrate these small shifts. The validity of our new measures can be inferred from the consistency of the results from different sets of measures.

Practitioner Notes

What is already known about this topic

A concept map (CM) is a knowledge assessment tool that can be used to evaluate student understanding of a topic and learning‐related progress.

However, there has been a lack of standardised, complex and domain‐general CM metrics.

Network theory has been shown to be useful in developing a standardised approach to CM evaluation.

What this paper adds

Based on the theory of cognitive development, we derived three standardised network measures of a CM: knowledge storage capacity, knowledge distributivity and knowledge retrieval.

The new measures were empirically found to discriminate between groups of students with different levels of competency.

Implications for practice and/or policy

The new measures provide unique information about learning‐related progress.

The newly developed measures enable educational researchers to make more objective evaluations of individual map elements, while simultaneously allowing for a holistic view of the quality of the knowledge structure of students.
Synthesis, pharmacological evaluations, and molecular docking studies on a new 1,3,4,11b‐tetrahydro‐1H‐fluoreno[9,1‐cd]azepine framework: Rigidification of D1 receptor selective 1‐phenylbenzazepines and discovery of a new 5‐HT6 receptor scaffold
Authors: Giri Rajan , Alberts Ian , Harding Wayne W.
Published: April 2020

The novel 1,3,4,11b‐tetrahydro‐1H‐fluoreno[9,1‐cd]azepine framework, a structurally rigidified variant of the 1‐phenylbenzazepine template, was synthesized via direct arylation as a key reaction. Evaluation of the binding affinities of the rigidified compounds across a battery of serotonin, dopamine, and adrenergic receptors indicates that this scaffold unexpectedly has minimal affinity for D1 and other dopamine receptors and is selective for the 5‐HT6 receptor. The affinity of these systems at the 5‐HT6 receptor is significantly influenced by electronic and hydrophobic interactions as well as the enhanced rigidity of the ligands. Molecular docking studies indicate that the reduced D1 receptor affinity of the rigidified compounds may be due in part to weaker H‐bonding interactions between the oxygenated moieties on the compounds and specific receptor residues. Key receptor–ligand H‐bonding interactions, salt bridges, and π–π interactions appear to be responsible for the 5‐HT6 receptor affinity of the compounds. Compounds 10 (6,7‐dimethoxy‐2,3,4,11b‐tetrahydro‐1H‐fluoreno[9,1‐cd]azepine) and 12 (6,7‐dimethoxy‐2‐methyl‐2,3,4,11b‐tetrahydro‐1H‐fluoreno[9,1‐cd]azepine) have been identified as structurally novel, high affinity (Ki = 5 nM), selective 5‐HT6 receptor ligands.
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

Prostate 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

Women 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

Background

Primary 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.

Objectives

To 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.

Methods

We 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.

Results

After 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.

Conclusions

Curative 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

Importance

Intraocular lens (IOL) calculations in post‐refractive cases remain a concern. Our study identifies improved options for surgeons.

Background

To 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).

Design

Retrospective consecutive cohort.

Participants

A total of 50 consecutive patients (72 eyes) at a private institution who underwent cataract surgery with prior laser refractive procedures.

Methods

Methods 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 Measures

Arithmetic 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.

Results

The 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 Relevance

Accuracy 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

Nonsyndromic 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

X‐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

Objectives

The 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 methods

Eighty 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.

Results

Peri‐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.

Conclusion

The 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

Background

Expression 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.

Methods

We 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.

Results

PD‐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.

Conclusions

Advanced 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

Aim

Biological 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.

Location

River Sabor, NE Portugal.

Methods

We 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.

Results

Geostatistical 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 conclusions

Incorporating 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

Current 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

Objectives

Pyruvate 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.

Methods

We 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.

Results

Of 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.

Conclusions

We 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 purpose

The 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)].

Methods

We 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.

Results

Paroxysmal 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).

Conclusion

Automated determination of ‘absence of pAF’ could be used to reduce the manual review workload associated with review of prolonged Holter ECG recordings.
JMY expression by Sertoli cells contributes to mediating spermatogenesis in mice
Authors: Liu Yue , Fan Jiaying , Yan Yan , Dang Xuening , Zhao Ran , Xu Yimei , Ding Zhide
Published: April 2020

Sertoli cells are crucial for spermatogenesis in the seminiferous epithelium because their actin cytoskeleton supports vesicular transport, cell junction formation, protein anchoring, and spermiation. Here, we show that a junction‐mediating and actin‐regulatory protein (JMY) affects the blood–tissue barrier (BTB) function through remodeling of the Sertoli cell junctional integrity and it also contributes to controlling endocytic vesicle trafficking. These functions are critical for the maintenance of sperm fertility since loss of Sertoli cell‐specific Jmy function induced male subfertility in mice. Specifically, these mice have (a) impaired BTB integrity and spermatid adhesion in the seminiferous tubules; (b) high incidence of sperm structural deformity; and (c) reduced sperm count and poor sperm motility. Moreover, the cytoskeletal integrity was compromised along with endocytic vesicular trafficking. These effects impaired junctional protein recycling and reduced Sertoli cell BTB junctional integrity. In addition, JMY interaction with actin‐binding protein candidates α‐actinin1 and sorbin and SH3 domain containing protein 2 was related to JMY activity, and in turn, actin cytoskeletal organization. In summary, JMY affects the control of spermatogenesis through the regulation of actin filament organization and endocytic vesicle trafficking in Sertoli cells.
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

The 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.
Remote sensing tracks daily radial wood growth of evergreen needleleaf trees
Authors: Eitel Jan U. H. , Griffin Kevin L. , Boelman Natalie T. , Maguire Andrew J. , Meddens Arjan J. H. , Jensen Johanna , Vierling Lee A. , Schmiege Stephanie C. , Jennewein Jyoti S.
Published: April 2020

Relationships between gross primary productivity (GPP) and the remotely sensed photochemical reflectance index (PRI) suggest that time series of foliar PRI may provide insight into climate change effects on carbon cycling. However, because a large fraction of carbon assimilated via GPP is quickly returned to the atmosphere via respiration, we ask a critical question—can PRI time series provide information about longer term gains in aboveground carbon stocks? Here we study the suitability of PRI time series to understand intra‐annual stem‐growth dynamics at one of the world's largest terrestrial carbon pools—the boreal forest. We hypothesized that PRI time series can be used to determine the onset (hypothesis 1) and cessation (hypothesis 2) of radial growth and enable tracking of intra‐annual tree growth dynamics (hypothesis 3). Tree‐level measurements were collected in 2018 and 2019 to link highly temporally resolved PRI observations unambiguously with information on daily radial tree growth collected via point dendrometers. We show that the seasonal onset of photosynthetic activity as determined by PRI time series was significantly earlier (p < .05) than the onset of radial tree growth determined from the point dendrometer time series which does not support our first hypothesis. In contrast, seasonal decline of photosynthetic activity and cessation of radial tree growth was not significantly different (p > .05) when derived from PRI and dendrometer time series, respectively, supporting our second hypothesis. Mixed‐effects modeling results supported our third hypothesis by showing that the PRI was a statistically significant (p < .0001) predictor of intra‐annual radial tree growth dynamics, and tracked these daily radial tree‐growth dynamics in remarkable detail with conditional and marginal coefficients of determination of 0.48 and 0.96 (for 2018) and 0.43 and 0.98 (for 2019), respectively. Our findings suggest that PRI could provide novel insights into nuances of carbon cycling dynamics by alleviating important uncertainties associated with intra‐annual vegetation response to climate change.