bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative genomics of the coconut crab and other decapod crustaceans: exploring the molecular basis of terrestrial adaptation
Authors: Veldsman Werner Pieter , Ma Ka Yan , Hui Jerome Ho Lam , Chan Ting Fung , Baeza J. Antonio , Qin Jing , Chu Ka Hou
Published: April 2021

Background

The complex life cycle of the coconut crab,Birgus latro, begins when an obligate terrestrial adult female visits the intertidal to hatch zoea larvae into the surf. After drifting for several weeks in the ocean, the post-larval glaucothoes settle in the shallow subtidal zone, undergo metamorphosis, and the early juveniles then subsequently make their way to land where they undergo further physiological changes that prevent them from ever entering the sea again. Here, we sequenced, assembled and analyzed the coconut crab genome to shed light on its adaptation to terrestrial life. For comparison, we also assembled the genomes of the long-tailed marine-living ornate spiny lobster,Panulirus ornatus, and the short-tailed marine-living red king crab,Paralithodes camtschaticus. Our selection of the latter two organisms furthermore allowed us to explore parallel evolution of the crab-like form in anomurans.

Results

All three assembled genomes are large, repeat-rich and AT-rich. Functional analysis reveals that the coconut crab has undergone proliferation of genes involved in the visual, respiratory, olfactory and cytoskeletal systems. Given that the coconut crab has atypical mitochondrial DNA compared to other anomurans, we argue that an abundance ofkif22and other significantly proliferated genes annotated with mitochondrial and microtubule functions, point to unique mechanisms involved in providing cellular energy via nuclear protein-coding genes supplementing mitochondrial and microtubule function. We furthermore detected in the coconut crab a significantly proliferated HOX gene,caudal, that has been associated with posterior development inDrosophila, but we could not definitively associate this gene with carcinization in the Anomura since it is also significantly proliferated in the ornate spiny lobster. However, a cuticle-associated coatomer gene,gammacop, that is significantly proliferated in the coconut crab, may play a role in hardening of the adult coconut crab abdomen in order to mitigate desiccation in terrestrial environments.

Conclusion

The abundance of genomic features in the three assembled genomes serve as a source of hypotheses for future studies of anomuran environmental adaptations such as shell-utilization, perception of visual and olfactory cues in terrestrial environments, and cuticle sclerotization. We hypothesize that the coconut crab exhibits gene proliferation in lieu of alternative splicing as a terrestrial adaptation mechanism and propose life-stage transcriptomic assays to test this hypothesis.
Mild increases in plasma creatinine after intermediate to high-risk abdominal surgery are associated with long-term renal injury
Authors: Joosten Alexandre , Ickx Brigitte , Mokhtari Zakaria , Van Obbergh Luc , Lucidi Valerio , Collange Vincent , Naili Salima , Ichai Philippe , Samuel Didier , Sa Cunha Antonio , Alexander Brenton , Legrand Matthieu , Taccone Fabio Silvio , Harrois Anatole , Duranteau Jacques , Vincent Jean-Louis , Rinehart Joseph , Van der Linden Philippe
Published: April 2021

Background

The potential relationship between a mild acute kidney injury (AKI) observed in the immediate postoperative period after major surgery and its effect on long term renal function remains poorly defined. According to the “Kidney Disease: Improving Global Outcomes” (KDIGO) classification, a mild injury corresponds to a KIDIGO stage 1, characterized by an increase in creatinine of at least 0.3 mg/dl within a 48-h window or 1.5 to 1.9 times the baseline level within the first week post-surgery. We tested the hypothesis that patients who underwent intermediate-to high-risk abdominal surgery and developed mild AKI in the following days would be at an increased risk of long-term renal injury compared to patients with no postoperative AKI.

Methods

All consecutive adult patients with a plasma creatinine value ≤1.5 mg/dl who underwent intermediate-to high-risk abdominal surgery between 2014 and 2019 and who had at least three recorded creatinine measurements (before surgery, during the first seven postoperative days, and at long-term follow up [6 months-2 years]) were included. AKI was defined using a “modified” (without urine output criteria) KDIGO classification as mild (stage 1 characterised by an increase in creatinine of > 0.3 mg/dl within 48-h or 1.5–1.9 times baseline) or moderate-to-severe (stage 2–3 characterised by increase in creatinine 2 to 3 times baseline or to ≥4.0 mg/dl). The exposure (postoperative kidney injury) and outcome (long-term renal injury) were defined and staged according to the same KDIGO initiative criteria. Development of long-term renal injury was compared in patients with and without postoperative AKI.

Results

Among the 815 patients included, 109 (13%) had postoperative AKI (81 mild and 28 moderate-to-severe). The median long-term follow-up was 360, 354 and 353 days for the three groups respectively (P = 0.2). Patients who developed mild AKI had a higher risk of long-term renal injury than those who did not (odds ratio 3.1 [95%CI 1.7–5.5]; p < 0.001). In multivariable analysis, mild postoperative AKI was independently associated with an increased risk of developing long-term renal injury (adjusted odds ratio 4.5 [95%CI 1.8–11.4]; p = 0.002).

Conclusions

Mild AKI after intermediate-to high-risk abdominal surgery is associated with a higher risk of long-term renal injury 1 y after surgery.
Right ventricular stroke work index by echocardiography in adult patients with pulmonary arterial hypertension
Authors: Jumatate Raluca , Ingvarsson Annika , Smith Gustav Jan , Roijer Anders , Ostenfeld Ellen , Waktare Johan , Rådegran Göran , Meurling Carl , Werther Evaldsson Anna
Published: April 2021

Background

In adult patients with pulmonary arterial hypertension (PAH), right ventricular (RV) failure may worsen rapidly, resulting in a poor prognosis. In this population, non-invasive assessment of RV function is challenging. RV stroke work index (RVSWI) measured by right heart catheterization (RHC) represents a promising index for RV function. The aim of the present study was to comprehensively evaluate non-invasive measures to calculate RVSWI derived by echocardiography (RVSWIECHO) using RHC (RVSWIRHC) as a reference in adult PAH patients.

Methods

Retrospectively, 54 consecutive treatment naïve patients with PAH (65 ± 13 years, 36 women) were analyzed. Echocardiography and RHC were performed within a median of 1 day [IQR 0–1 days]. RVSWIRHCwas calculated as: (mean pulmonary arterial pressure (mPAP)—mean right atrial pressure (mRAP)) x stroke volume index (SVI)RHC. Four methods for RVSWIECHOwere evaluated: RVSWIECHO-1 = Tricuspid regurgitant maximum pressure gradient (TRmaxPG) x SVIECHO, RVSWIECHO-2 = (TRmaxPG-mRAPECHO) x SVIECHO, RVSWIECHO-3 = TR mean gradient (TRmeanPG) x SVIECHOand RVSWIECHO-4 = (TRmeanPG–mRAPECHO) x SVIECHO. Estimation of mRAPECHOwas derived from inferior vena cava diameter.

Results

RVSWIRHCwas 1132 ± 352 mmHg*mL*m−2. In comparison with RVSWIRHCin absolute values, RVSWIECHO-1and RVSWIECHO-2was significantly higher (p < 0.001), whereas RVSWIECHO-4was lower (p < 0.001). No difference was shown for RVSWIECHO-3(p = 0.304). The strongest correlation, with RVSWIRHC, was demonstrated for RVSWIECHO-2(r = 0.78,p < 0.001) and RVSWIECHO-1( r = 0.75,p < 0.001). RVSWIECHO-3and RVSWIECHO-4had moderate correlation (r = 0.66 and r = 0.69,p < 0.001 for all). A good agreement (ICC) was demonstrated for RVSWIECHO-3(ICC = 0.80, 95% CI 0.64–0.88,p < 0.001), a moderate for RVSWIECHO-4(ICC = 0.73,95% CI 0.27–0.87,p < 0.001) and RVSWIECHO-2(ICC = 0.55, 95% CI − 0.21–0.83,p < 0.001). A poor ICC was demonstrated for RVSWIECHO-1(ICC = 0.45, 95% CI − 0.18–0.77,p < 0.001). Agreement of absolute values for RVSWIECHO-1was − 772 ± 385 (− 50 ± 20%) mmHg*mL*m−2, RVSWIECHO-2− 600 ± 339 (-41 ± 20%) mmHg*mL*m−2, RVSWIECHO-342 ± 286 (5 ± 25%) mmHg*mL*m−2and for RVSWIECHO-4214 ± 273 (23 ± 27%) mmHg*mL*m−2.

Conclusion

The correlation with RVSWIRHCwas moderate to strong for all echocardiographic measures, whereas only RVSWIECHO-3displayed high concordance of absolute values. The results, however, suggest that RVSWIECHO-1or RVSWIECHO-3could be the preferable echocardiographic methods. Prospective studies are warranted to evaluate the clinical utility of such measures in relation to treatment response, risk stratification and prognosis in patients with PAH.
Comparison of first trimester dating methods for gestational age estimation and their implication on preterm birth classification in a North Indian cohort
Authors:   GARBH-Ini Study Group, Vijayram Ramya , Damaraju Nikhita , Xavier Ashley , Desiraju Bapu Koundinya , Thiruvengadam Ramachandran , Misra Sumit , Chopra Shilpa , Khurana Ashok , Wadhwa Nitya , Rengaswamy Raghunathan , Sinha Himanshu , Bhatnagar Shinjini
Published: April 2021

Background

Different formulae have been developed globally to estimate gestational age (GA) by ultrasonography in the first trimester of pregnancy. In this study, we develop an Indian population-specific dating formula and compare its performance with published formulae. Finally, we evaluate the implications of the choice of dating method on preterm birth (PTB) rate. This study’s data was from GARBH-Ini, an ongoing pregnancy cohort of North Indian women to study PTB.

Methods

Comparisons between ultrasonography-Hadlock and last menstrual period (LMP) based dating methods were made by studying the distribution of their differences by Bland-Altman analysis. Using data-driven approaches, we removed data outliers more efficiently than by applying clinical parameters. We applied advanced machine learning algorithms to identify relevant features for GA estimation and developed an Indian population-specific formula (Garbhini-GA1) for the first trimester. PTB rates of Garbhini-GA1 and other formulae were compared by estimating sensitivity and accuracy.

Results

Performance of Garbhini-GA1 formula, a non-linear function of crown-rump length (CRL), was equivalent to published formulae for estimation of first trimester GA (LoA, − 0.46,0.96 weeks). We found that CRL was the most crucial parameter in estimating GA and no other clinical or socioeconomic covariates contributed to GA estimation. The estimated PTB rate across all the formulae including LMP ranged 11.27–16.50% with Garbhini-GA1 estimating the least rate with highest sensitivity and accuracy. While the LMP-based method overestimated GA by 3 days compared to USG-Hadlock formula; at an individual level, these methods had less than 50% agreement in the classification of PTB.

Conclusions

An accurate estimation of GA is crucial for the management of PTB. Garbhini-GA1, the first such formula developed in an Indian setting, estimates PTB rates with higher accuracy, especially when compared to commonly used Hadlock formula. Our results reinforce the need to develop population-specific gestational age formulae.
Exploring antenatal care utilization and intimate partner violence in Benin - are lives at stake?
Authors: Idriss-Wheeler Dina , Yaya Sanni
Published: April 2021

Background

The republic of Benin ranks in the bottom third of countries recently assessed for ANC coverage and its Ministry of Family and National Solidarity (2009) reported close to 70% of Beninese women suffered abuse at least once in their lifetime. Utilization of antenatal care (ANC) services is key to positive health outcomes for both mother and infant. This study examined the impact of intimate partner violence (IPV) on the utilization of ANC services in Benin using both the basic 4 visit model (ANC-4) and the updated WHO recommended 8-visit model (ANC-8).

Methods

Data used for this study were collected from the nationally representative 2017–2018 Benin Demographic Health Survey (BDHS) on ever-partnered women aged 15–49 who had completed both reproductive maternal health and domestic violence modules of the survey. Descriptive statistics and multivariate logistic regression analysis were performed to determine significant factors associated with ANC utilization in Benin.

Results

Over 40% of the women (n = 3084) reported experience of IPV in their lifetime. Findings revealed that women who ever experienced IPV (OR 0.753, 95% CI: 0.628–0.901; p = 0.002) had 25% less odds of accessing the basic four ANC visits. IPV was not found to be a factor in accessing at least eight ANC visits. With increasing number of children, there was less likelihood of accessing at least four and at least eight visits. Being in the richest quintile (OR 5.490, 95% CI 3.907–7.714; p < 0.000 for ANC-4; OR, 5.781, 95% CI: 3.208–10.41; p < 0.000), making decisions on household and health care (OR 1.279, 95% CI: 1.042–1.569 for ANC-4; OR, 1.724; 95% CI: 1.170–2.540; p = 0.006 for ANC-8), and getting paid cash for work increased the chances of utilizing ANC-four (OR 1.451, 95% CI: 1.122–1.876; 0.005) but not for ANC-eight. Belonging to the Muslim faith decreased the odds of ANC utilization compared to all other religions.

Conclusion

This work revealed key areas for maternal health policy makers and service providers in Benin to appropriately plan effective policies (i.e., alleviate poverty; equitable health services access; cultural sensitivity) and necessary interventions (i.e. ANC education, IPV prevention, paid employment, alcohol cessation) to increase utilization of ANC.
A scoping review of the literature featuring research ethics and research integrity cases
Authors: Armond Anna Catharina Vieira , Gordijn Bert , Lewis Jonathan , Hosseini Mohammad , Bodnár János Kristóf , Holm Soren , Kakuk Péter
Published: April 2021

Background

The areas of Research Ethics (RE) and Research Integrity (RI) are rapidly evolving. Cases of research misconduct, other transgressions related to RE and RI, and forms of ethically questionable behaviors have been frequently published. The objective of this scoping review was to collect RE and RI cases, analyze their main characteristics, and discuss how these cases are represented in the scientific literature.

Methods

The search included cases involving a violation of, or misbehavior, poor judgment, or detrimental research practice in relation to a normative framework. A search was conducted in PubMed, Web of Science, SCOPUS, JSTOR, Ovid, and Science Direct in March 2018, without language or date restriction. Data relating to the articles and the cases were extracted from case descriptions.

Results

A total of 14,719 records were identified, and 388 items were included in the qualitative synthesis. The papers contained 500 case descriptions. After applying the eligibility criteria, 238 cases were included in the analysis. In the case analysis, fabrication and falsification were the most frequently tagged violations (44.9%). The non-adherence to pertinent laws and regulations, such as lack of informed consent and REC approval, was the second most frequently tagged violation (15.7%), followed by patient safety issues (11.1%) and plagiarism (6.9%). 80.8% of cases were from the Medical and Health Sciences, 11.5% from the Natural Sciences, 4.3% from Social Sciences, 2.1% from Engineering and Technology, and 1.3% from Humanities. Paper retraction was the most prevalent sanction (45.4%), followed by exclusion from funding applications (35.5%).

Conclusions

Case descriptions found in academic journals are dominated by discussions regarding prominent cases and are mainly published in the news section of journals. Our results show that there is an overrepresentation of biomedical research cases over other scientific fields compared to its proportion in scientific publications. The cases mostly involve fabrication, falsification, and patient safety issues. This finding could have a significant impact on the academic representation of misbehaviors. The predominance of fabrication and falsification cases might diverge the attention of the academic community from relevant but less visible violations, and from recently emerging forms of misbehaviors.
Plasma and cerebrospinal fluid inflammation and the blood-brain barrier in older surgical patients: the Role of Inflammation after Surgery for Elders (RISE) study
Authors:   RISE Study Group, Vasunilashorn Sarinnapha M. , Ngo Long H. , Dillon Simon T. , Fong Tamara G. , Carlyle Becky C. , Kivisäkk Pia , Trombetta Bianca A. , Vlassakov Kamen V. , Kunze Lisa J. , Arnold Steven E. , Xie Zhongcong , Inouye Sharon K. , Libermann Towia A. , Marcantonio Edward R.
Published: April 2021

Background

Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation.

Methods

We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids.

Results

Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p < .01 for both) and IL-6 (PO1MO r = 0.48, p < .01) were observed, with higher correlations on PO1MO compared with baseline.

Conclusions

In this elective surgical sample of older adults, BBB integrity was similar between baseline and PO1MO, plasma-CSF correlations were observed for CRP and IL-6, plasma levels of all three markers (CRP, IL-6, and YKL-40) increased from PREOP to PO1MO, and CSF levels of only CRP increased between the two time points. Our identification of potential promising plasma markers of inflammation in the CNS may facilitate the early identification of patients at greatest risk for neuroinflammation and its associated adverse cognitive outcomes.
Identification of aberrant innate and adaptive immunity based on changes in global gene expression in the blood of adults with autism spectrum disorder
Authors: Horiuchi Fumie , Yoshino Yuta , Kumon Hiroshi , Hosokawa Rie , Nakachi Kiwamu , Kawabe Kentaro , Iga Jun-ichi , Ueno Shu-ichi
Published: April 2021

Background

Autism spectrum disorder (ASD) is characterized as a neurodevelopmental disorder, and one of the main hypotheses regarding its cause is genetic factors. A previous meta-analysis of seven microarray studies and one RNA sequencing (RNA-seq) study using the blood of children with ASD identified dysregulation of gene expressions relevant to the immune system. In this study, we explored changes in global gene expression as the phenotype of ASD in the blood of adults with ASD.

Methods

We recruited an RNA-seq cohort (ASD vs. control; n = 6 each) and a replication cohort (ASD vs. control; n = 19 each) and conducted RNA-seq to explore changes in global gene expression. We then subjected the significantly up- and downregulated genes to gene ontology (GO) and core analyses. Weighted gene correlation network analysis (WGCNA) was performed with all 11,617 genes detected in RNA-seq to identify the ASD-specific gene network.

Results

In total, 117 significantly up- and 83 significantly downregulated genes were detected in the ASD compared with the control group, respectively (p < 0.05 and q < 0.05). GO analysis revealed that the aberrant innate and adaptive immunity were more obvious in the 117 upregulated than in the 83 downregulated genes. WGCNA with core analysis revealed that one module including many immune-related genes was associated with the natural killer cell signaling pathway. In the results for the replication cohort, significant changes with same trend found in RNA-seq data were confirmed for MAFB (p = 0.046), RPSAP58 (p = 0.030), and G2MK (p = 0.004).

Limitations

The sample size was relatively small in both the RNA-seq and replication cohorts. This study examined the mRNA expression level, so the interaction between mRNA and protein remains unclear. The expression changes between children and adults with ASD were not compared because only adults with ASD were targeted.

Conclusions

The dysregulated gene expressions confirmed in the blood of adults with ASD were relevant to the dysfunction of innate and adaptive immunity. These findings may aid in understanding the pathogenesis of ASD.
Acute high-grade acromioclavicular joint dislocation patients treated with titanium cable insertion under a homemade guider
Authors: Wang Jun , Cui Yongfeng , Zhang Yuhang , Yin Hang
Published: April 2021

Backgrounds

To describe a new technique for implanting a double-bundle titanium cable to treat acromioclavicular (AC) joint dislocation via the new guider, and evaluate clinic outcomes.

Methods

A retrospective study of patients treated for acute high-grade acromioclavicular joint dislocation from June 2016 to January 2020 in our trauma center, twenty patients with AC joint dislocation were managed with double-bundle titanium cable. It includes the following steps: (1) Put the guider under the coracoid close to the cortical; (2) drill proximal clavicle; (3) place the titanium cable; (4) perforate distal clavicle, (5) reset the acromioclavicular joint and lock titanium cable; and (6) suture the acromioclavicular ligament. An independent reviewer conducted functional testing of these patients, including the use of coracoclavicular distance (CCD), visual analog scale (VAS) scores, and Constant–Murley scores (CMS).

Results

All patients are presented following at a median duration of 15 months (12-24months) after the surgery. All patients based on X-ray evaluation and clinic evaluation. The median CCD was 7.5 (6–14) mm, the VAS score was 0.55 (0-2), the CMS score was 95.5 (92-99). One patient had subluxation again at the final follow-up based on X-ray examination.

Conclusions

This study demonstrates that the AC joint fixation anatomically with double-bundle titanium, acquired excellent outcomes in terms of the recovery of shoulder joint function and radiographic outcomes. It has a low complication rate and need not remove the hardware.
Five semi analytical and numerical simulations for the fractional nonlinear space-time telegraph equation
Authors: Khater Mostafa M. A. , Park Choonkil , Lee Jung Rye , Mohamed Mohamed S. , Attia Raghda A. M.
Published: April 2021

The accuracy of analytical obtained solutions of the fractional nonlinear space–time telegraph equation that has been constructed in (Hamed and Khater in J. Math., 2020) is checked through five recent semi-analytical and numerical techniques. Adomian decomposition (AD), El Kalla (EK), cubic B-spline (CBS), extended cubic B-spline (ECBS), and exponential cubic B-spline (ExCBS) schemes are used to explain the matching between analytical and approximate solutions, which shows the accuracy of constructed traveling wave solutions. In 1880, Oliver Heaviside derived the considered model to describe the cutting-edge or voltage of an electrified transmission. The matching between solutions has been explained by plotting them in some different sketches.
The impact of central foveal thickness and integrity of the outer retinal layers in the visual outcome of uveitic macular edema
Authors: Alvarez-Guzman Carlos , Bustamante-Arias Andres , Colorado-Zavala Maria F. , Rodriguez-Garcia Alejandro
Published: April 2021

Background

To analyze the relationship between the central foveal thickness (CFT) and the integrity of the ellipsoid portion of inner segments (EPIS) and interdigitating zone (IZ) retinal layers in the visual outcome of uveitic macular edema (UME).

Methods

Prospective, observational, and cross-sectional study of eyes with UME. Spectral-domain optical coherence tomography (SD-OCT) macular morphological pattern, CFT, and integrity of the outer retinal layers were analyzed. We arranged the data by EPIS or IZ integrity and contrasted it with student t-test (quantitative variables) and Fisher exact test or χ² distribution (categorical variables) to evaluate visual impairment and retinal measures. Receiver operator curve (ROC) estimation and logistic regression (probit) assessed if the sample´s variance could be associated with IZ or EPIS integrity.

Results

We included 145 SD-OCT macular scans from 45 patients at different stages of UME. Cystoid macular edema (CME) increased the risk of severe (P ≤ 0.0162) and moderate visual loss (P ≤ 0.0032). The highest CFT values occurred in patients with moderate (478.11 ± 167.62 μm) and severe (449.4 ± 224.86 μm) visual loss. Of all morphological patterns of macular edema, only CME showed a statistically significant relationship with severe visual impairment (44.92%, p = 0.0035, OR 4.29 [1.62–11.4]). Likewise, an increased probability of severe visual loss correlated negatively with both, IZ (37.93%, P ≤ 0.001, OR 10.02) and EPIS (38.98%, P ≤ 0.001, OR 13.1) disruption. A CFT > 337 μm showed a higher probability of IZ (AUROC = 0.7341, SEN 77.59%, ESP 65.52) and EPIS (AUROC = 0.7489, SEN 76.37%, ESP 65.12%) loss of integrity. Moreover, when BCVA reached 0.44 LogMAR (≤ 20/50 Snellen eq.), it was more likely to have IZ (AUROC = 0.8706, ESP 88.51%, SEN 77.59%) and EPIS (AUROC = 0.8898, ESP 88.3%, SEN 76.27) disruption.

Conclusions

Significantly increased CFT has a higher probability for EPIS and IZ disruption, which significantly increases the risk for irreversible visual loss in eyes with UME. Evaluating these layers’ integrity by optical coherence tomography helps predict the visual outcome and make the right therapeutic decisions.

Trial registration The study was registered on April 13, 2020, at the Instituto Tecnologico y de Estudios Superiores de Monterrey Research Committee (License No. COFEPRIS 20 CI 19 039 002), project registration No. P000338-CAVICaREMU-CI-CR002, and the Ethics Committee (License No. CONBIOETICA 19 CEI 011-2016-10-17), project registration No. P000338-CAVICaREMU-CEIC-CR002
Mental health law in Algeria: new amendments, old concerns
Authors: Benmebarek Zoubir
Published: April 2021

Since 2018 Algeria has had a new mental health law intended to be more practical and in line with international standards for patients’ rights and supervision of coercive measures. Despite its simpler formulation compared with the previous law it remains far from what psychiatrists need and what patients hope for. Some chapters are confusing and difficult to grasp. Like previous mental health laws, it is unlikely that the current law will actually be applied, owing to the huge gap between the core text and the available services.
Artificial Intelligence and Radiomics in Head and Neck Cancer Care: Opportunities, Mechanics, and Challenges
Authors: van Dijk Lisanne V. , Fuller Clifton D.
Published: April 2021

The advent of large-scale high-performance computing has allowed the development of machine-learning techniques in oncologic applications. Among these, there has been substantial growth in radiomics (machine-learning texture analysis of images) and artificial intelligence (which uses deep-learning techniques for “learning algorithms”); however, clinical implementation has yet to be realized at scale. To improve implementation, opportunities, mechanics, and challenges, models of imaging-enabled artificial intelligence approaches need to be understood by clinicians who make the treatment decisions. This article aims to convey the basic conceptual premises of radiomics and artificial intelligence using head and neck cancer as a use case. This educational overview focuses on approaches for head and neck oncology imaging, detailing current research efforts and challenges to implementation.
TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors
Authors: Tagawa Scott T. , Balar Arjun V. , Petrylak Daniel P. , Kalebasty Arash Rezazadeh , Loriot Yohann , Fléchon Aude , Jain Rohit K. , Agarwal Neeraj , Bupathi Manojkumar , Barthelemy Philippe , Beuzeboc Philippe , Palmbos Phillip , Kyriakopoulos Christos E. , Pouessel Damien , Sternberg Cora N. , Hong Quan , Goswami Trishna , Itri Loretta M. , Grivas Petros
Published: April 2021

PURPOSE

Patients with metastatic urothelial carcinoma (mUC) who progress on platinum-based combination chemotherapy (PLT) and checkpoint inhibitors (CPIs) have limited options that offer objective response rates (ORRs) of approximately 10% with a median overall survival (OS) of 7-8 months. Sacituzumab govitecan (SG) is a TROP-2–directed antibody-drug conjugate with an SN-38 payload that has shown preliminary activity in mUC.

METHODS

TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973 ) is a multicohort, open-label, phase II, registrational study. Cohort 1 includes patients with locally advanced or unresectable or mUC who had progressed after prior PLT and CPI. Patients received SG 10 mg/kg on days 1 and 8 of 21-day cycles. The primary outcome was centrally reviewed ORR; secondary outcomes were progression-free survival, OS, duration of response, and safety.

RESULTS

Cohort 1 included 113 patients (78% men; median age, 66 years; 66.4% visceral metastases; median of three [range, 1-8] prior therapies). At a median follow-up of 9.1 months, the ORR was 27% (31 of 113; 95% CI, 19.5 to 36.6); 77% had decrease in measurable disease. Median duration of response was 7.2 months (95% CI, 4.7 to 8.6 months), with median progression-free survival and OS of 5.4 months (95% CI, 3.5 to 7.2 months) and 10.9 months (95% CI, 9.0 to 13.8 months), respectively. Key grade ≥ 3 treatment-related adverse events included neutropenia (35%), leukopenia (18%), anemia (14%), diarrhea (10%), and febrile neutropenia (10%), with 6% discontinuing treatment because of treatment-related adverse events.

CONCLUSION

SG is an active drug with a manageable safety profile with most common toxicities of neutropenia and diarrhea. SG has notable efficacy compared with historical controls in pretreated mUC that has progressed on both prior PLT regimens and CPI. The results from this study supported accelerated approval of SG in this population.
On quarks and the origin of QCD: Partons and baryons from intrinsic states
Authors: Trinhammer Ole L.
Published: April 2021

We create quarks from baryons in stead of constituting baryons from quarks. The quantum fields of QCD are generated via the exterior derivative (momentum form) of baryon wave functions on an intrinsic configuration space, the Lie group U(3). Local gauge transformations correspond to coordinate translations in the intrinsic space. A proton spin structure function and a proton magnetic moment are derived. We show how the spectrum of unflavoured baryons, the N and Delta resonances, can be understood from a mass Hamiltonian on the intrinsic space and note how our model resolves the problem of colour confinement. We calculate an approximate value for the relative neutron-to-proton mass shift and give an exact value for the neutron mass. We predict neutral charge singlets that may be interpreted as neutral pentaquarks at LHCb.
The Effect of Chloroacetophenone on the Inducing Capacity of Hensen’s Node
Authors: Lakshmi M. S.
Published: April 2021

The effect of chloroacetophenone at concentrations of 0·0005 M, 0·001 M, and 0·0015 M on the capacity of induction of Hensen’s node has been studied. A fall in the percentage of induction with increase of concentration of CAP is seen. A qualitative fall of induction is also observed as evidenced by a reduction in the number of strong inductions and increase in cases of absence of induction with increase of concentration from 0·0005 M to 0·0015 M. There were no strong inductions after 0·0015 M CAP treatment.
Identification of dividing, determined sensory neuron precursors in the mammalian neural crest
Authors: Greenwood Amy L. , Turner Eric E. , Anderson David J.
Published: April 2021

Sensory and autonomic neurons of the vertebrate peripheral nervous system are derived from the neural crest. Here we use the expression of lineage-specific transcription factors as a means to identify neuronal subtypes that develop in rat neural crest cultures grown in a defined medium. Sensory neurons, identified by expression of the POU-domain transcription factor Brn-3.0, develop from dividing precursors that differentiate within 2 days following emigration from the neural tube. Most of these precursors generate sensory neurons even when challenged with BMP2, a factor that induces autonomic neurogenesis in many other cells in the explants. Moreover, BMP2 fails to prevent expression of the sensory-specific basic helix-loop-helix (bHLH) transcription factors neurogenin1, neurogenin2 and neuroD, although it induces expression of the autonomic-specific bHLH factor MASH1 and the paired homeodomain factor Phox2a in other cells. These data suggest that there are mitotically active precursors in the mammalian neural crest that can generate sensory neurons even in the presence of a strong autonomic-inducing cue. Further characterization of the neurons generated from such precursors indicates that, under these culture conditions, they exhibit a proprioceptive and/or mechanosensory, but not nociceptive, phenotype. Such precursors may therefore correspond to a lineally (Frank, E. and Sanes, J. (1991) Development 111, 895-908) and genetically (Ma, Q., Fode, C., Guillemot, F. and Anderson, D. J. (1999) Genes Dev. 13, in press) distinct subset of early-differentiating precursors of large-diameter sensory neurons identified in vivo.
Mutants of cubitus interruptus that are independent of PKA regulation are independent of hedgehog signaling
Authors: Chen Yang , Cardinaux Jean-René , Goodman Richard H. , Smolik Sarah M.
Published: April 2021

Hedgehog (HH) is an important morphogen involved in pattern formation during Drosophila embryogenesis and disc development. cubitus interruptus (ci) encodes a transcription factor responsible for transducing the hh signal in the nucleus and activating hh target gene expression. Previous studies have shown that CI exists in two forms: a 75 kDa proteolytic repressor form and a 155 kDa activator form. The ratio of these forms, which is regulated positively by hh signaling and negatively by PKA activity, determines the on/off status of hh target gene expression. In this paper, we demonstrate that the exogenous expression of CI that is mutant for four consensus PKA sites [CI(m1-4)], causes ectopic expression of wingless (wg) in vivo and a phenotype consistent with wg overexpression. Expression of CI(m1-4), but not CI(wt), can rescue the hh mutant phenotype and restore wg expression in hh mutant embryos. When PKA activity is suppressed by expressing a dominant negative PKA mutant, the exogenous expression of CI(wt) results in overexpression of wg and lethality in embryogenesis, defects that are similar to those caused by the exogenous expression of CI(m1-4). In addition, we demonstrate that, in cell culture, the mutation of any one of the three serine-containing PKA sites abolishes the proteolytic processing of CI. We also show that PKA directly phosphorylates the four consensus phosphorylation sites in vitro. Taken together, our results suggest that positive hh and negative PKA regulation of wg gene expression converge on the regulation of CI phosphorylation.
Refined analysis of early symbiotic steps of the Rhizobium-Medicago interaction in relationship with microtubular cytoskeleton rearrangements
Authors: Timmers Antonius C. J. , Auriac Marie-Christine , Truchet Georges
Published: April 2021

In situ immunolocalization of tubulin revealed that important rearrangements occur during all the early symbiotic steps in the Medicago/R. meliloti symbiotic interaction. Microtubular cytoskeleton (MtC) reorganizations were observed in inner tissues, first in the pericycle and then in the inner cortex where the nodule primordium forms. Subsequently, major MtC changes occurred in outer tissues, associated with root hair activation and curling, the formation of preinfection threads (PITs) and the initiation and the growth of an infection network. From the observed sequence of MtC changes, we propose a model which aims to better define, at the histological level, the timing of the early symbiotic stages. This model suggests the existence of two opposite gradients of cell differentiation controlling respectively the formation of division centers in the inner cortex and plant preparation for infection. It implies that (i) MtC rearrangements occur in pericycle and inner cortex earlier than in the root hair, (ii) the infection process proceeds prior to the formation of the nodule meristem, (iii) the initial primordium prefigures the future zone II of the mature nodule and (iv) the nodule meristem derives from the nodule primordium. Finally, our data also strongly suggest that in alfalfa PIT differentiation, a stage essential for successful infection, requires complementary signaling additional to Nod factors.
Replication of macronuclear DNA in the cytoplasm of Tetrahymena pyriformis
Authors: Andersen H. A.
Published: April 2021

Previous experiments showed that a synchronous population of Tetrahymena could divide even though DNA replication was blocked during the latter half of the preceding S-period by addition of methotrexate plus uridine (M + U). Furthermore, it was found that the DNA fraction which was in replication at the time of inhibition became localized in the cytoplasm following elimination from the nucleus at the time of division. When the inhibitory treatment (M + U) was removed prior to or at the time of the cell division the cells were found to engage in new DNA replication and continue growth. Two questions arose from these studies. First, is the DNA replication normal following release from M + U? Second, what is the fate of the cytoplasmic DNA? In the present paper DNA replication has been studied using incorporation of 5-bromodeoxyuridine and centrifugation of the labelled DNA in CsCl gradients. It is concluded that the DNA which finished replication prior to the effect of the M + U treatment replicates again during the S-period of the next cell generation. On the other hand, the DNA fraction which was stalled in replication and subsequently eliminated from the nucleus also replicates in the cytoplasm in the next generation but during G2 period, out of phase with the undamaged nuclear DNA. The cytoplasmic DNA replication appeared to be a continuation of the replication initiated in the nucleus in the previous generation.
Differences in density of concanavalin a-binding sites due to differences in surface morphology of suspended normal and transformed 3t3 fibroblasts
Authors: Collard J. G. , Temmink J. H. M.
Published: April 2021

Calculations of the density of Concanavalin A (Con A)-binding sites on normal and transformed fibroblasts have, as yet, been based on the unproven assumption that suspended cells are smooth spheres. We studied the surface morphology of suspended normal and transformed fibroblasts with scanning and transmission electron microscopes, and found a large difference in surface morphology between suspended normal and transformed 3T3 cells. When this difference in surface morphology was taken into account, the estimated cell surface area of normal 3T3 cells was approximately seven times larger than that of transformed 3T3 cells. Since equal numbers of 3H-Con A molecules are bound on normal and transformed cells, the density of Con A-binding sites is approximately seven times greater on transformed than on normal 3T3 cells.

The difference in density of Con A-binding sites between normal and transformed fibroblasts might be sufficient to explain the difference in agglutination response, as originally suggested by Burger, and may also be the cause of the different degrees of clustering of Con A-binding sites on the plasma membrane of these cells.
Membrane specialization in the rat epididymis. I. Rod-shaped intramembrane particles in the apical (mitochondria-rich) cell
Authors: Brown Dennis , Montesano Roberto
Published: April 2021

Following freeze-fracture of the rat epididymis, a population of cells whose apical, but not baso-lateral, plasma membrane contains elongated intramembrane particles was found in the initial segment. From their size, shape and distribution, these cells are assumed to be the socalled apical cells of this segment. Apical cells also contain the enzyme, carbonic anhydrase which, together with the presence of rod-shaped particles on their membranes, permits their classification as ‘mitochondria-rich’ cells, a specialized cell type found in some transporting epithelia. On the basis of these observations, we suggest that the apical cells may play a role in fluid and/or electrolyte transport in the initial segment of the epididymis.
Anomalous preferences of cultured macrophages for hydrophobic and roughened substrata
Authors: Rich Abby , Harris Albert K.
Published: April 2021

Peritoneal macrophages were plated out on a series of artificial haptotactic substrata consisting of grid patterns of vacuum-evaporated palladium metal alternating with hydrophobic untreated polystyrene and with hydrophilic sulphonated polystyrene. By their active locomotion the macrophages accumulated preferentially onto the less hydrophilic of either pair of these alternative substrata. This order of substratum preference is precisely the opposite to that shown by fibroblastic cells. Macrophages were also found to accumulate preferentially onto roughened culture surfaces as opposed to smooth ones, which is again opposite to the behaviour of fibroblasts. These opposite substratum preferences shown by macrophages may reflect physical as well as functional differences in their surfaces, and could serve as assay criteria for macrophages and cell types putatively equivalent to macrophages.
Conformational changes induced by salt in complexes of histones and superhelical nuclear dna
Authors: Levin Jeremy M. , Cook Peter R.
Published: April 2021

When HeLa cells are lysed in solutions containing a non-ionic detergent and 0·75 M-NaCl, structures are released that retain many of the morphological features of nuclei. These nucleoids contain all the nuclear DNA, RNA and the ‘core’ histones, but few other proteins characteristic of chromatin. Their DNA is intact. The core histones dissociate on raising the salt concentration. We have probed the structure of nucleoid-histone complexes using the intercalating dye, ethidium, or the RNA polymerase of Escherichia coli. Both have a higher affinity for superhelical DNA than they do for relaxed DNA. The binding of ethidium is measured fluorometrically, and using this probe we find that the DNA of nucleoids containing all the core histones behaves as if it were supercoiled slightly positively. As the salt concentration is increased, free energy characteristic of negative supercoiling appears between 0·92 M and 0·95 M-NaCl. This transition, which is reversible in the presence of the arginine-rich histones, occurs without dissociation of these histones from the DNA and so must reflect a conformational change in the complex. In contrast to the results with ethidium, we find that RNA polymerase can detect the presence of some negative free energy of supercoiling in nucleoids containing the core histones. The transformations of the free energy that can assist the binding of ethidium and RNA polymerase are discussed.
Studies on heteromorphic selfincompatibility systems: The cytochemistry and ultrastructure of the tapetum of Primula obconica
Authors: Stevens Valda A. M. , Murray B. G.
Published: April 2021

This paper describes the cytochemistry and ultrastructure of the developing tapetum in Primula obconica, a plant with a heteromorphic, sporophytic self-incompatibility system. The tapetum is of the secretory type and cytochemical tests have shown that when it breaks down proteinaceous (esterase) and lipidie components are deposited on the developing pollen grains. Acid phosphatase, a marker of gametophytic enzyme activity, is confined to the cytoplasm and intine of the developing pollen. Ultrastructural studies show that prior to its dissolution the tapetum undergoes a number of changes. In the early stages of development the tapetum is rich in ribosomes and rough endoplasmic reticulum, but following the breakdown of the tapetal cell wall the main components of the cytoplasm are densely staining spherical bodies surrounded by ribosomes and orbicular bodies, which appear to be confined to the cell periphery. As the cells break down, rod-like fibrils can be seen amongst the degenerate organelles and within the bacular cavities of the pollen. On dehiscence the pollen has a lipidie coating in addition to the fibrillar material in the pollen wall and the remnants of the tapetum can be seen adhering to the fibrous layer of the anther wall. Thus the mature, binucleate pollen of P. obconica is demonstrated to carry wall materials of sporophytic origin.
DNA repair in mouse embryo fibroblasts: I. Decline in ultraviolet-induced incision rate accompanies cell transformation
Authors: Elliott G. C. , Johnson R. T.
Published: April 2021

In this paper we examine DNA repair in the mouse. Using stringently applied inhibitors of DNA synthesis (hydroxyurea and l-β-D-arabinofuranosylcytosine) after ultraviolet irradiation we have quantitated an early step in the repair process -the frequency of single-strand DNA breaks, products of enzymic incision -in fibroblasts and epithelial cells grown in vitro from adults and embryos of different ages.

We find that initial rates of incision are very similar in the earliest-passage fibroblasts, regardless of donor age, resembling the rates measured in other rodents while being considerably less than in diploid human fibroblasts. Consistently higher rates of incision are found in adult kidney epithelial cells. With increasing passage number the embryo cultures change with respect to growth rate and chromosome constitution, undergoing spontaneous transformation to established heteroploid cultures. This sequence is accompanied by characteristic changes in initial rates of inhibitor-sensitive incision. An early increase in incision rate, at a time when the cultures are enriched with tetraploid cells, is succeeded by progressive reduction in rate as the cultures become overtly transformed into permanent lines and heteroploidy is established. The lowest rate of incision occurs in a transformed line cloned from a late-passage culture. The decline in incision rate associated with transformation is accompanied by reduced unscheduled DNA synthesis (UDS). The sensitivity to inhibitors of UDS levels in the mouse cultures has been found to vary considerably; inhibitors are most effective in slowly proliferating cultures and apparently not at all when cultures are growing rapidly despite their ability to accumulate DNA breaks in these cells. Caution is needed, therefore, in the interpretation of repair data obtained in the presence of these commonly used inhibitors of DNA synthesis.