Nevin Manimala

PLoS Biol. 2021 Mar 1;19(3):e3001107. doi: 10.1371/journal.pbio.3001107. Online ahead of print.

ABSTRACT

Recent concerns about the reproducibility of science have led to several calls for more open and transparent research practices and for the monitoring of potential improvements over time. However, with tens of thousands of new biomedical articles published per week, manually mapping and monitoring changes in transparency is unrealistic. We present an open-source, automated approach to identify 5 indicators of transparency (data sharing, code sharing, conflicts of interest disclosures, funding disclosures, and protocol registration) and apply it across the entire open access biomedical literature of 2.75 million articles on PubMed Central (PMC). Our results indicate remarkable improvements in some (e.g., conflict of interest [COI] disclosures and funding disclosures), but not other (e.g., protocol registration and code sharing) areas of transparency over time, and map transparency across fields of science, countries, journals, and publishers. This work has enabled the creation of a large, integrated, and openly available database to expedite further efforts to monitor, understand, and promote transparency and reproducibility in science.

PMID:33647013 | DOI:10.1371/journal.pbio.3001107

PLoS Comput Biol. 2021 Mar 1;17(3):e1008781. doi: 10.1371/journal.pcbi.1008781. Online ahead of print.

ABSTRACT

The naïve antibody/B-cell receptor (BCR) repertoires of different individuals ought to exhibit significant functional commonality, given that most pathogens trigger an effective antibody response to immunodominant epitopes. Sequence-based repertoire analysis has so far offered little evidence for this phenomenon. For example, a recent study estimated the number of shared (‘public’) antibody clonotypes in circulating baseline repertoires to be around 0.02% across ten unrelated individuals. However, to engage the same epitope, antibodies only require a similar binding site structure and the presence of key paratope interactions, which can occur even when their sequences are dissimilar. Here, we search for evidence of geometric similarity/convergence across human antibody repertoires. We first structurally profile naïve (‘baseline’) antibody diversity using snapshots from 41 unrelated individuals, predicting all modellable distinct structures within each repertoire. This analysis uncovers a high (much greater than random) degree of structural commonality. For instance, around 3% of distinct structures are common to the ten most diverse individual samples (‘Public Baseline’ structures). Our approach is the first computational method to find levels of BCR commonality commensurate with epitope immunodominance and could therefore be harnessed to find more genetically distant antibodies with same-epitope complementarity. We then apply the same structural profiling approach to repertoire snapshots from three individuals before and after flu vaccination, detecting a convergent structural drift indicative of recognising similar epitopes (‘Public Response’ structures). We show that Antibody Model Libraries derived from Public Baseline and Public Response structures represent a powerful geometric basis set of low-immunogenicity candidates exploitable for general or target-focused therapeutic antibody screening.

PMID:33647011 | DOI:10.1371/journal.pcbi.1008781

PLoS Negl Trop Dis. 2021 Mar 1;15(3):e0009117. doi: 10.1371/journal.pntd.0009117. eCollection 2021 Mar.

ABSTRACT

In Burkina Faso, onchocerciasis was no longer a public health problem when the WHO Onchocerciasis Control Programme in West Africa closed at the end in 2002. However, epidemiological surveillance carried out from November 2010 to February of 2011, showed a recrudescence of infection in the Cascades Region. This finding was made at a time when ivermectin, a drug recommended for the treatment of both onchocerciasis and lymphatic filariasis, had been distributed in this area since 2004 for the elimination of lymphatic filariasis. It was surprising that ivermectin distributed for treating lymphatic filariasis had not prevented the recrudescence of onchocerciasis. Faced with this situation, the aim of our study was to evaluate the effectiveness of ivermectin on the onchocerciasis parasite. The percentage reduction in microfilarial load after treatment with ivermectin was used as a proxy measure for assessing possible resistance. A cohort study was carried out with 130 individuals who had tested positive for microfilariae of Onchocerca volvulus in 2010 using microscopic examination of skin-snip biopsies from five endemic villages. Subjects were followed from July 2011 to June 2012. The microfilarial load of each individual was enumerated by skin-snip biopsy in 2010, prior to the first ivermectin treatment against onchocerciasis under community guidelines. All individuals received two ivermectin treatments six months apart. In 2012, the microfilarial loads were determined again, six months after the second round of ivermectin and the reductions in parasite loads were calculated to measure the impact of the drug. The percentage reduction of the microfilarial loads ranged from 87% to 98% in the villages. In all villages, there was a statistically significant difference between the average microfilarial loads in 2010 and 2012. The level of reduction of microfilarial loads suggests that ivermectin is effective against the recrudescent population of O. volvulus in Cascades Region of Burkina Faso. Further investigations would be necessary to determine the causes of the recrudescence of onchocerciasis. (For French language abstract, see S1 Alternative Language Abstract-Translation of the Abstract into French by the authors.).

PMID:33647010 | DOI:10.1371/journal.pntd.0009117

Med Sci Monit. 2021 Mar 1;27:e929617. doi: 10.12659/MSM.929617.

ABSTRACT

BACKGROUND Renal parenchymal damage and scarring usually is associated with urinary tract infection (UTI), whereas the impact of vesicoureteral reflux (VUR) on the kidneys is unclear. We aimed to compare kidneys with all grades of VUR (grades Io-V) and those without VUR by using direct radionuclide cystography, voiding cystourethrography, and findings from 99mTc-DMSA scintigraphy (DMSA scan). MATERIAL AND METHODS The present analysis included 253 renal ureteral units (RUU) from 129 children with VUR and recurrent UTI and children with a single febrile UTI associated with abnormal ultrasonographic findings. The 6 grades of VUR (Io, I, II, III, IV, and V) and 35 RUUs without VUR were divided into 4 groups: 1. Non-dilated VUR (grades Io-II); 2. Mildly dilated VUR (grade III); 3. Dilated VUR (grades IV-V); and 4. The control group. RESULTS DMSA scanning showed significant differences between the groups with non-dilated VUR, grade III VUR, grades IV-V VUR, and the control group in kidney width (χ²=30.5; P<0.001); position and shape (χ²=30.6; P<0.001); intensity of activity (χ²=38.1; P<0.001); distribution of activity (χ²=34.5; P<0.001); and existence of scars (χ²=16; P<0.001). The probability of abnormalities on DMSA scans increased with the VUR grade. However, inside the groups of dilated and non-dilated VUR we found no significant statistical differences between those characteristics. CONCLUSIONS Our results indicate that kidneys without VUR or with non-dilated lateral VUR and dilated VUR on the contralateral side represent 2 different categories of parenchymal changes.

PMID:33647007 | DOI:10.12659/MSM.929617

Neurologist. 2021 Mar 4;26(2):41-46. doi: 10.1097/NRL.0000000000000315.

ABSTRACT

BACKGROUND: Advanced neuroimaging can identify patients who can most benefit from reperfusion treatment, discriminating between ischemic core and penumbra area in a quick and accurate manner. Despite core-penumbra mismatch being an independent prognostic factor, computed tomography perfusion (CTP) assessment is still debated in hyperacute decision-making. The authors aimed to study a novel CTP mismatch score in emergency settings and to investigate its relation with clinical outcome in acute ischemic stroke patients treated with intravenous thrombolysis (IVT).

METHODS: Neuroimaging and clinical data of 226 consecutive acute ischemic stroke patients were analyzed. The study population was divided into 5 different CTP scores: (0) without perfusion deficit, (1) only penumbra, (2) penumbra > core, (3) core ≥ penumbra, (4) only core. For differences in outcome between treated and nontreated patients, and among CTP core-penumbra groups to be assessed, the authors have evaluated the outcome in terms of National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) at discharge and symptomatic intracerebral hemorrhage.

RESULTS: A decrease in NIHSS was statistically greater in IVT-treated patients compared to nontreated patients showing only penumbra (ΔNIHSS%: 80.0% vs. 50.0%; P=0.0023) or no perfusion deficit (ΔNIHSS%: 89.4% vs. 61.5%; P=0.027) on CTP maps. The same trend was found in other groups without significant difference. A significant correlation was found in IVT patients between core/penumbra score and outcome in terms of ΔNIHSS (Kendall τ=-0.19; P=0.004).

CONCLUSIONS: The authors proposed a novel immediate CTP assessment to score perfusion mismatch in emergency settings to guide clinicians’ decision-making for aggressive treatment and to prevent stroke-related disability.

PMID:33646988 | DOI:10.1097/NRL.0000000000000315

Neurologist. 2021 Mar 4;26(2):32-35. doi: 10.1097/NRL.0000000000000329.

ABSTRACT

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2), which is involved in the inflammatory atherosclerotic process, has emerged as an independent risk factor for atheromatous vascular events. Its impact on coronary disease has already been demonstrated, however, its influence in cerebrovascular etiology is still unknown. We aimed to observe and describe the potential association between Lp-PLA2 levels and the etiologic subtype of ischemic stroke.

METHODS: Unicentric, observational, and prospective cohort study of consecutive patients with acute ischemic stroke, admitted in a comprehensive stroke center. Patients with incomplete investigation or coexisting causes were excluded. Lp-PLA2 was dosed in peripheral blood between day 3 and 14 postevent with “Lp-PLA2-SNIBE” kit. Statistical significance was set for P<0.05.

RESULTS: A total of 96 patients were enrolled, with mean age of 75.31±11.88 years, 41 males (42.7%); 12.5% with lacunar stroke, 16.7% atherothrombotic, 46.9% cardioembolic, and 24% embolic stroke of undetermined source (ESUS). The level of Lp-PLA2 was different between etiologies (F=2.982, P=0.035), being lower in ESUS (143.3±42.8 ng/mL). There were no significant associations with previous vascular risk factors, history of ischemic stroke and modified-Rankin scale (mRS) score 3 months postevent. In ESUS patients, Lp-PLA2 was not associated with cervical ultrasound findings or frequent supraventricular extrasystoles.

CONCLUSIONS: Lp-PLA2 levels are different between etiologic subtypes of ischemic stroke, being lower in ESUS patients. The results of this study reinforce the existence of distinct pathophysiological mechanisms in patients with ESUS. Multicenter clinical trials with larger sample sizes are needed to clarify the role Lp-PLA2 on the etiology of stroke.

PMID:33646986 | DOI:10.1097/NRL.0000000000000329

IEEE Trans Image Process. 2021 Mar 1;PP. doi: 10.1109/TIP.2021.3061276. Online ahead of print.

ABSTRACT

We propose objective, image-based techniques for quantitative evaluation of facial skin gloss that is consistent with human judgments. We use polarization photography to obtain separate images of surface and subsurface reflections, and rely on psychophysical studies to uncover and separate the influence of the two components on skin gloss perception. We capture images of facial skin at two levels, macro-scale (whole face) and meso-scale (skin patch), before and after cleansing. To generate a broad range of skin appearances for each subject, we apply photometric image transformations to the surface and subsurface reflection images. We then use linear regression to link statistics of the surface and subsurface reflections to the perceived gloss obtained in our empirical studies. The focus of this paper is on within-subject gloss perception, that is, on visual differences among images of the same subject. Our analysis shows that the contrast of the surface reflection has a strong positive influence on skin gloss perception, while the darkness of the subsurface reflection (skin tone) has a weaker positive effect on perceived gloss. We show that a regression model based on the concatenation of statistics from the two reflection images can successfully predict relative gloss differences.

PMID:33646950 | DOI:10.1109/TIP.2021.3061276

IEEE Trans Pattern Anal Mach Intell. 2021 Mar 1;PP. doi: 10.1109/TPAMI.2021.3062644. Online ahead of print.

ABSTRACT

Domain Adaptation (DA) attempts to transfer knowledge in labeled source domain to unlabeled target domain without requiring target supervision. Recent advanced methods conduct DA mainly by aligning domain distributions. However, the performances of these methods suffer extremely when source and target domains encounter a large domain discrepancy. We argue this limitation may attribute to insufficient domain-specialized feature exploring, because most works merely concentrate on domain-general feature learning while integrating totally-shared convolutional networks (convnets). In this paper, we relax the completely-shared convnets assumption and propose Domain Conditioned Adaptation Network, which introduces domain conditioned channel attention module to excite channel activation separately for each domain. Such a partially-shared convnets module allows domain-specialized features in low-level to be explored appropriately. Furthermore, we develop Generalized Domain Conditioned Adaptation Network to automatically determine whether domain channel activations should be modeled separately in each attention module. Then, the critical domain-dependent knowledge could be adaptively extracted according to the domain statistics gap. Meanwhile, to effectively align high-level feature distributions across two domains, we further deploy feature adaptation blocks after task-specific layers, which will explicitly mitigate the domain discrepancy. Extensive experiments on four cross-domain benchmarks demonstrate our approaches outperform existing methods, especially on very tough cross-domain learning tasks.

PMID:33646945 | DOI:10.1109/TPAMI.2021.3062644

Prague Med Rep. 2021;122(1):25-33. doi: 10.14712/23362936.2021.3.

ABSTRACT

It has been stated that the effectiveness of pectopexy method for the treatment of pelvic organ prolapse (POP) is similar to sacrocolpopexy. We aimed to search the effects of pectopexy method to the quality of life, sexual function and urinary incontinence. Thirty-one patients who were operated for POP with the technique of laparoscopic pectouteropexy/pectocolpopexy between January 2016 and November 2017 were included the study. Exclusion criteria were pelvic inflammatory disease, suspect of malignancy, pregnancy, prior POP or continence surgery. Quality of life inventories were (P-QOL, PISQ-12, UDI-6, IIQ-7) recorded preoperatively and at the postoperative third month. Results were compared statistically. The percentage of patients with menopause was 67.7% (n=21) and with reproductive term was 32.3% (n=10). Mean prolapse related quality of life inventory (P-QOL) score was 83.45 ± 8.7 (64-98) preoperatively and 8.61 ± 6.4 (0-23) postoperatively (p&lt;0.05). The preoperative and postoperative score of quality of life inventories for urinary symptoms were 20 (15-21) and 2 (0-9) for IIQ-7 and 13 (3-18) and 4 (0-11) for UDI-6, respectively (p&lt;0.05). The mean PISQ-12 sexual quality of life inventory score was 29.61 ± 4.8 (14-38) preoperatively and 7.1 ± 3.2 (1-13) postoperatively. According to our results laparoscopic pectopexy offers a feasible, safe and comfortable alternative for apical prolapse surgery.

PMID:33646939 | DOI:10.14712/23362936.2021.3

Prague Med Rep. 2021;122(1):14-24. doi: 10.14712/23362936.2021.2.

ABSTRACT

There are reports that in patients with aSAH (aneurysmal subarachnoid hemorrhage), LTF (lamina terminalis fenestration) reduces the rate of shunt-needed hydrocephalus via facilitation of CSF (cerebrospinal fluid) dynamic, diminished leptomeningeal inflammation, and decreased subarachnoid fibrosis. Regarding the conflicting results, this study was conducted to evaluate the effects of LTF on decreased shunt-needed hydrocephalus in patients with aSAH. A cross-sectional retrospective study was carried out to survey all patients with confirmed aSAH operated from March 2011 to September 2016 in an academic vascular center (Rasool Akram Hospital in Tehran, Iran). Of a total of 151 patients, 72 patients were male and 79 were female. The mean age of the participants was 51 years. A transiently CSF diversion (EVD – external ventricular drainage) was performed (the acute hydrocephalus rate) on 21 patients (13.9%). In 36 patients (23.8%), aneurysm occlusion with LTF and in 115 patients (76.2%) only aneurysm occlusion surgery was performed. In hydrocephalus follow-up after surgery, 13 (12%) patients needed shunt insertion (the rate of shunt-needed hydrocephalus). The statistical analysis demonstrated no significant relation between LTF and shunt-needed hydrocephalus. Confirmation of the hypothesis that LTF may decrease the rate of shunt-needed hydrocephalus can significantly decrease morbidity, mortality, and treatment costs of shunting (that is a simple, but a potentially dangerous procedure). So, it is advised to plan and perform an RCT (randomized controlled trial) that can remove the confounding factors, match the groups, and illustrate the exact effect of LTF on shunt-needed hydrocephalus.

PMID:33646938 | DOI:10.14712/23362936.2021.2