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Dominic J Allocco, Anita A Joshi, Keith D DawkinsBoston Scientific Corporation, Natick, MA, USAAbstract: Everolimus-eluting stents (EES) have become the most commonly implanted coronary stents worldwide. This review describes and analyzes the clinical data supporting the use of EES, focusing primarily on published, randomized, controlled trials. Everolimuseluting stents have been shown to have less restenosis, stent thrombosis, and periprocedural myocardial infarction compared with earlier generation paclitaxel-eluting stents (PES). Lower rates of adverse events for EES compared with PES were generally seen in all subgroups, with the notable exception of patients with diabetes mellitus. There have been fewer, randomized, clinical trials comparing EES with either sirolimus-eluting stents or zotarolimus-eluting stents, although very good results with EES have been observed in the trials that have been performed. Recent clinical trial data suggest that this excellent safety and efficacy profile is maintained in a next-generation EES designed to have improved mechanical properties and radiopacity.Keywords: drug-eluting stents, everolimus, Xience V, Promus, Promus ElementVideo Abstract: http://dvpr.es/allocco

AIMS: To describe the eligibility criteria (i.e. study participant inclusion and exclusion rules) employed in alcohol treatment outcome research and to identify predictors of their use. DESIGN: The eligibility criteria of 683 alcohol treatment outcome studies conducted between 1970 and 1998 were coded reliably into 14 general categories. Predictors of the use of eligibility criteria were then examined. FINDINGS: Patients were most often ruled ineligible for research studies because of their level of alcohol problems (39.1% of studies), comorbid psychiatric problems (37.8%), past or concurrent utilization of alcohol treatment (31.8%), co-occurring medical conditions (31.6%), and because they were deemed non-compliant and unmotivated (31.5%). The number of eligibility criteria employed in studies increased from the 1970s through the 1990s, and was positively associated with funding from the US National Institute of Alcohol Abuse and Alcoholism (NIAAA) and from the private sector, lack of an inpatient/residential treatment condition, presence of a pharmacotherapy, and use of a randomized, multiple-condition design. Principal investigators with doctoral degrees used more eligibility criteria than those with lower degrees. CONCLUSION: Participant eligibility criteria are extensively employed in alcohol treatment outcome research, and vary significantly across historical periods, funders and research designs. Researchers should report the details of subject eligibility criteria and excluded patients more fully, and, evaluate how eligibility criteria affect the cost, feasibility, and generalizability of treatment outcome research. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the feasibility of diffusion tensor brain imaging at 0.55T with comparisons against 3T., Methods: Diffusion tensor imaging data with 2 mm isotropic resolution was acquired on a cohort of five healthy subjects using both 0.55T and 3T scanners. The signal-to-noise ratio (SNR) of the 0.55T data was improved using a previous SNR-enhancing joint reconstruction method that jointly reconstructs the entire set of diffusion weighted images from k-space using shared-edge constraints. Quantitative diffusion tensor parameters were estimated and compared across field strengths. We also performed a test-retest assessment of repeatability at each field strength., Results: After applying SNR-enhancing joint reconstruction, the diffusion tensor parameters obtained from 0.55T data were strongly correlated ( R 2 ≥ 0 . 70 $$ {R}^2\ge 0.70 $$ ) with those obtained from 3T data. Test-retest analysis showed that SNR-enhancing reconstruction improved the repeatability of the 0.55T diffusion tensor parameters., Conclusion: High-resolution in vivo diffusion MRI of the human brain is feasible at 0.55T when appropriate noise-mitigation strategies are applied., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

In this study, Indian pulse proteins from cowpeas, yellow peas, green gram, and horse gram were used to create plant-based meatball analogs. The nutritional composition, molecular functional groups, color, and texture of meatball analogs T1, T2, and T3 and mutton meatballs were thoroughly analyzed. T1 had highest protein (51%) compared to control (19%), T2 (45%), and T3 (36%), but fiber content (1.26%) was less in T1 compared to control (2.86%), T2 (3.33%), and T3 (3.49%). The more is fibrous raw materials; lower will be the hardness of meat analogs. T1 had consistent fracturability, hardness, cohesiveness, and adhesiveness, and was superior in springiness, gumminess, resilience, and chewiness compared to T2, T3, and control. Sensory evaluation results reported that T1 was more consistent with control sample in terms of color, texture, juiciness, and overall acceptability and no significant difference was reported among the two ( p  > .05). The L* and b* values of T1 were more consistent with control compared to other two. Potato starch, salt, spice mix, coriander leaves, beet root pulp, jackfruit seed powder, rose water, carboxy methyl cellulose and rehydrated mushrooms showed a positive impact on sensory and textural attributes. The Fourier transform infrared (FTIR) spectra revealed that the protein fractions were not affected by the processing conditions. FTIR results confirm the presence of secondary structural components such as α-helix, β-sheet, and β-turn. The interaction between the starchy fibrous material and protein fractions were identified clearly via FTIR. The T1 meat analog was superior in terms of color, organoleptic and textural properties compared to T2 and T3 and more close to mutton meatballs. These results will open up the new horizons in this area and pave the way for the large production and marketing of plant based meat analogs, which will reduces the health and sustainable raising issues from consumption of mutton meat., Competing Interests: DECLARATION OF CONFLICTING INTERESTSThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

There has been a concerted effort by the neuroimaging community to establish standards for computational methods for data analysis that promote reproducibility and portability. In particular, the Brain Imaging Data Structure (BIDS) specifies a standard for storing imaging data, and the related BIDS App methodology provides a standard for implementing containerized processing environments that include all necessary dependencies to process BIDS datasets using image processing workflows. We present the BrainSuite BIDS App, which encapsulates the core MRI processing functionality of BrainSuite within the BIDS App framework. Specifically, the BrainSuite BIDS App implements a participant-level workflow comprising three pipelines and a corresponding set of group-level analysis workflows for processing the participant-level outputs. The Anatomical Pipeline extracts cortical surface models from a T1-weighted (T1w) MRI. It then performs surface-constrained volumetric registration to align the T1w MRI to a labeled anatomical atlas, which is used to delineate anatomical regions of interest in the MRI brain volume and on the cortical surface models. The Diffusion Pipeline processes diffusion-weighted imaging (DWI) data, with steps that include coregistering the DWI data to the T1w scan, correcting for susceptibility-induced geometric image distortion, and fitting diffusion models to the DWI data. The Functional Pipeline performs fMRI processing using a combination of FSL, AFNI, and BrainSuite tools. It coregisters the fMRI data to the T1w image, then transforms the data to the anatomical atlas space and to the Human Connectome Project's grayordinate space. The outputs of each pipeline can then be processed during group-level analysis. The outputs of the Anatomical Pipeline and the Diffusion Pipeline are analyzed using the BrainSuite Statistics Toolbox in R (bstr), which provides functionality for hypothesis testing and statistical modeling. The outputs of the Functional Pipeline can be analyzed using atlas-based or atlas-free statistical methods during group-level processing. These analyses include the application of BrainSync, which synchronizes the time-series data temporally and enables comparison of resting-state or task-based fMRI data across scans. We also present the BrainSuite Dashboard quality control system, which provides a browser-based interface for reviewing the outputs of individual modules of the participant-level pipelines across a study in real-time as they are generated. BrainSuite Dashboard facilitates rapid review of intermediate results, enabling users to identify processing errors and make adjustments to processing parameters if necessary. The comprehensive functionality included in the BrainSuite BIDS App provides a mechanism for rapidly deploying the BrainSuite workflows into new environments to perform large-scale studies. We demonstrate the capabilities of the BrainSuite BIDS App using structural, diffusion, and functional MRI data from the Amsterdam Open MRI Collection's Population Imaging of Psychology dataset.

Competing Interests: Mohammad Javed Ali received royalties from Springer for the textbook “Principles and Practice of Lacrimal Surgery” and “Atlas of Lacrimal Drainage Disorders” and the videobook “Lacrimal Drainage Surgery.” Other authors have no financial or conflicts of interest to disclose.

Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders of skin-homing T cells causing chronic inflammation. These disorders cause impairment of the immune environment, which leads to severe infections and/or sepsis due to dysbiosis. In this study, we elucidated the host-microbial interaction in CTCL that occurs during the phototherapeutic treatment regime and determined whether modulation of the skin microbiota could beneficially affect the course of CTCL. EL4 T-cell lymphoma cells were intradermally grafted on the back of C57BL/6 mice. Animals were treated with conventional therapeutics such as psoralen + UVA (PUVA) or UVB in the presence or absence of topical antibiotic treatment (neomycin, bacitracin, and polymyxin B sulphate) as an adjuvant. Microbial colonisation of the skin was assessed to correlate with disease severity and tumour growth. Triple antibiotic treatment significantly delayed tumour occurrence ( p = 0.026), which prolonged the survival of the mice ( p  = 0.033). Allocation to phototherapeutic agents PUVA, UVB, or none of these, along with antibiotic intervention, reduced the tumour growth significantly ( p  = 0.0327, p  ≤ 0.0001, p  ≤ 0.0001 respectively). The beta diversity indices calculated using the Bray-Curtis model showed that the microbial population significantly differed after antibiotic treatment ( p  = 0.001). Upon modulating the skin microbiome by antibiotic treatment, we saw an increase in commensal Clostridium species, e.g., Lachnospiraceae sp. ( p = 0.0008), Ruminococcaceae sp. ( p  = 0.0001)., Blautia sp. ( p  = 0.007) and a significant reduction in facultative pathogens Corynebacterium sp. ( p = 0.0009), Pelomonas sp. ( p  = 0.0306), Streptococcus sp. ( p  ≥ 0.0001), Pseudomonas sp. ( p  = 0.0358), and Cutibacterium sp. ( p  = 0.0237). Intriguingly, we observed a significant decrease in Staphylococcus aureus frequency ( p  = 0.0001) but an increase in the overall detection frequency of the Staphylococcus genus, indicating that antibiotic treatment helped regain the microbial balance and increased the number of non-pathogenic Staphylococcus populations. These study findings show that modulating microbiota by topical antibiotic treatment helps to restore microbial balance by diminishing the numbers of pathogenic microbes, which, in turn, reduces chronic inflammation, delays tumour growth, and increases survival rates in our CTCL model. These findings support the rationale to modulate the microbial milieu during the disease course of CTCL and indicate its therapeutic potential., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dey, Vieyra-Garcia, Joshi, Trajanoski and Wolf.)

The objectives of the present work were to explore film forming ability of mucilaginous polysaccharides obtained from Cassia uniflora seeds and improving its bioadhesive potential by thiolation for drug delivery and other applications. Thiolation was achieved by esterification reaction with thioglycolic acid. The modification was confirmed by performing and comparing its zeta potential, DSC, and spectrophotometric characterization by FTIR and NMR with unmodified mucilaginous polysaccharide. The modified mucilaginous polysaccharides FTIR spectra showed an additional absorption band at 2565 cm -1 and new shifts appeared in the 1 H (δ 3.24 and at δ 3.44 ppm) and 13 C NMR spectra's (21.56 ppm) confirming the esterification of mucilaginous polysaccharides. The prepared films of thiolated and unmodified mucilaginous polysaccharides were evaluated for various parameters like thickness, pH, and weight measurement, The film formulation had a thickness of 0.16 to 0.18 mm, pH in the range of 6.79 to 7.09 and weight uniformity 0.89 to 0.94 mg. The results reveal that the films based on thiolated material improved bioadhesive properties after thiolation. The SEM photographs revealed a smooth surface of film formulations. The diclofenac-loaded film of thiolated mucilaginous polysaccharide also showed >1.5-fold an increase in in-vitro drug release and exhibited non Fickian transport mechanism. These findings could increase the possible applications of chemically modified-thiolated mucilaginous polysaccharides of Cassia uniflora seeds in drug delivery., Competing Interests: Declaration of competing interest “All the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.”, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Staphylococcus aureus is an aerobic Gram-positive spherical bacterium known to cause a broad range of infections worldwide. It is a major cause of infective skin and soft infections and severe and life-threatening conditions, such as pneumonia, bloodstream infections, and endocarditis. The emergence of drug-resistant strains of S aureus , particularly methicillin-resistant S aureus (MRSA), has become a significant concern in the healthcare community. Antibiotic-resistant S aureus is commonly acquired in hospitals and long-term care facilities. It often affects patients with weakened immune systems, those undergoing invasive medical procedures, or those who have been hospitalized for extended periods. In the US, S aureus is known to cause potentially fatal illnesses, such as toxic shock syndrome (TSS) and acute-onset toxic shock syndrome (TSS), which are characterized by fever and hypotension. It develops resistance to antibiotics through several mechanisms, such as the production of enzymes that inactivate antibiotics, target site modification, efflux pumps, and plasmid-mediated resistance. Therefore, preventing the spread of drug-resistant S aureus is needed, and there is an urgent need to explore novel approaches in the development of anti- staphylococcal agents. This article reviews the principal infections caused by S aureus, major virulence factors, mechanisms of resistance development, and nanotechnology-based solutions for the control of drug-resistant S aureus ., (© 2023 The Author(s).)

Tracheitis sicca is a rare condition where there is drying and crusting of tracheal mucosa which may lead to tracheal obstruction and respiratory distress. Reported here is a case of young boy, who presented with cough, cold and respiratory distress worsening over a period of 5 days. On admission the patient was administered with dexamethasone and was intubated. However, saturation was not maintained despite assisted ventilation, and multiple episodes of self extubation always presented with stridor. Hence, otorhinolaryngology reference was taken and decision was taken to perform laryngotracheobronchoscopy. Endoscopy done showed extensive crusting in the trachea causing complete obstruction of airway above the level of carina. The crusting was meticulously removed, sent for culture, and the obstruction was relieved. The patient maintained saturation after the procedure, and was ultimately extubated and discharged., Competing Interests: Conflict of interestNone., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Non-timber forest products (NTFPs) are known to provide livelihoods for forest-based communities across the world. While ensuring the sustainability of NTFP harvests is a key challenge, optimizing the production of NTFPs through appropriate silvicultural practices is also critical for forest-based economies. In Central India, the suitability of fire or pruning practices for enhancing the production of leaves of the tendu tree ( Diospyros melanoxylon ) has been much debated. While villagers commonly adopt annual litter fires, the state Forest Department urges leaf collectors to adopt the more labor-intensive practice of pruning. On the other hand, conservationists recommend completely hands-off management (no fire or pruning). In this study, we compared leaf production from the competing practices of litter fire, pruning, pruning-with-fire, and hands-off management, that are experimented with in community-managed forests. We checked for confounding factors such as tree canopy cover, presence of tendu trees, and inherent differences in forest type. We conducted the study during the pre-harvest season from March to May 2020 in villages in the northern Gadchiroli district of Maharashtra, India. We found that pruning and pruning-with-fire lead to higher root sprout production and, in turn, higher leaf production per unit area when compared to litter fire and the control (no pruning or fire). Fire alone led to a negative impact on leaf production. Implementing pruning instead of litter fire, however, comes with labor costs. Its adoption is therefore linked with the institutional arrangements for tendu management and marketing that shape community perception of costs. गौण वन उत्पादने जगभरातील वन-आधारित समुदायांसाठी उपजीविका म्हणून महत्त्वाची आहेत. त्यांच्या शाश्वत उपलब्धतेसाठी तसेच त्यांच्यावर अवलंबून आजीविकांच्या दृष्टीने वन उपजाच्या नियोजन पद्धतींचा वनवृक्षशास्त्राच्या दृष्टीने अभ्यास होणे गरजेचे आहे. मध्य भारतातील वन-आधारित समुदाय अनेक वर्ष तेंदू वृक्षाच्या पानांना (म्हणजे बिडी-पत्त्याला) निरनिराळ्या पद्धतीने संकलित करीत आहेत व त्याकरिता निरनिराळ्या पद्धतीने नियोजन करीत आहेत. झाडाची झुडपी वाढ करून, पाने हाता जवळ वाढवणे हा त्यातील मुख्य उद्देश आहे. यामध्ये झाडाच्या रोपांची मुळाशी छाटणी करणे (खुट/बेल कटाई) किंवा, जंगलातील पाचोळा पेटवणे, किंवा या दोन्ही पद्धती एकत्रित वापरणे ('छाटणी-व-आग') अशा पद्धतींचा समावेश आहे. अलीकडे काही लोक तेंदू संवर्धनासाठी झाडाची विना-नियोजन वाढ होऊ देतात (म्हणजे विना आग आणि विना खुट कटाईने). यातील कोणत्या पद्धतीने प्रती हेक्टरी सर्वात जास्त तेंदू पाने तयार होतात याचा अभ्यास आम्ही केला. यासाठी आम्ही उत्तर गडचिरोली, महाराष्ट्र येथील काही गावांच्या सामुहिक वन क्षेत्रात मार्च ते मे २०२० मध्ये वेगवेगळ्या नियोजन पद्धतीमध्ये होणाऱ्या तेंदूपत्ता उत्पन्नाचा पद्धतशीर अभ्यास केला. एकूण आम्हाला असे दिसले की, आग वापरण्यापेक्षा तेंदूच्या रोपांची मुळाशी केलेली छाटणी व 'छाटणी-व-आग' या पद्धती अधिक पानांचे उत्पन्न देतात. आम्ही पाहिले की स्थानिक जंगल प्रकार, त्याची दाटी, व तेंदू वृक्षाची निकटता या निकषांमुळे पानांच्या उत्पन्नात नियोजन पद्धतीपेक्षा जास्त परिणाम होत नाही. परंतु यातील कोणतीही पद्धत वापरताना व वन-आधारित उपजीविका सांभाळत, तसेच सामुहिक वन नियोजन करताना काही व्यावहारिक अडचणी आहेत. त्यांचावरही आम्ही या अभ्यासात विचार केला आहे., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The New York Botanical Garden 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Aim: N95 masks are recommended for the healthcare providers (HCPs) taking care of patients with coronavirus disease 2019. However, the use of these masks hampers communication. We aimed to evaluate the effect of N95 masks on speech comprehension among listeners and vocal efforts (VEs) of the HCPs., Materials and Methods: This prospective study involved 50 HCPs. We used a single observer with normal hearing to assess the difficulty in comprehension, while VE was estimated in HCPs. The speech reception threshold (SRT), speech discrimination score (SDS), and VEs were evaluated initially without using N95 mask and then repeated with HCPs wearing N95 mask., Results: The use of masks resulted in a statistically significant increase in mean SRT [4.25 (1.65) dB] and VE [2.6 (0.69)], with simultaneous decrease in mean SDS [19.2 (8.77)] (all p-values < 0.0001). Moreover, demographic parameters including age, sex, and profession were not associated with change in SRT, SDS, and VE (all p-values > 0.05)., Conclusion: Though use of N95 masks protects the HCPs against the viral infection, it results in decreased speech comprehension and increased VEs. Moreover, these issues are universal among the HCPs and are applicable to the general public as well., Competing Interests: Conflict of InterestThere is no conflicts of interest among the authors., (© Association of Otolaryngologists of India 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that significantly affects the patient's quality of life. A disrupted skin barrier, type 2 cytokine-dominated inflammation, and microbial dysbiosis with increased Staphylococcus aureus colonization are critical components of AD pathogenesis. Patients with AD exhibit decreased expression of antimicrobial peptides (AMPs) which is linked to increased colonization by Staphylococcus aureus . The skin microbiome itself is a source of several AMPs. These host- and microbiome-derived AMPs define the microbial landscape of the skin based on their differential antimicrobial activity against a range of skin microbes or their quorum sensing inhibitory properties. These are particularly important in preventing and limiting dysbiotic colonization with Staphylococcus aureus . In addition, AMPs are critical for immune homeostasis. In this article, we share our perspectives about the implications of microbial derived AMPs in AD patients and their potential effects on overlapping factors involved in AD. We argue and discuss the potential of bacterial AMPs as therapeutics in AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Joshi, Vocanson, Nicolas, Wolf and Patra.)

Background Mechanical circulatory support devices, such as the intra-aortic balloon pump (IABP) and Impella, are often used in patients on veno-arterial extracorporeal life support (VA-ECLS) with cardiogenic shock despite limited supporting clinical trial data. Methods and Results Hospitalizations for cardiogenic shock from 2016 to 2018 were identified from the National Inpatient Sample. Trends in the use of VA-ECLS with and without an IABP or Impella were assessed semiannually. Multivariable logistic regression and general linear regression evaluated the association of Impella and IABP use with in-hospital outcomes. Overall, 12 035 hospitalizations with cardiogenic shock and VA-ECLS were identified, of which 3115 (26%) also received an IABP and 1880 (16%) an Impella. Use of an Impella with VA-ECLS substantially increased from 10% to 18% over this period ( P <0.001), whereas an IABP modestly increased from 25% to 26% ( P <0.001). In-hospital mortality decreased 54% to 48% for VA-ECLS only, 61% to 58% for VA-ECLS with an Impella, and 54% to 49% for VA-ECLS with an IABP ( P <0.001 each). Most (57%) IABPs or Impellas were placed on the same day as VA-ECLS. After adjustment, there were no differences in in-hospital mortality or length of stay with the addition of an IABP or Impella compared with VA-ECLS alone. Conclusions From 2016 to 2018 in the United States, use of an Impella and IABP with VA-ECLS significantly increased. More than half of Impellas and IABPs were placed on the same day as VA-ECLS, and the use of a second mechanical circulatory support device did not impact in-hospital mortality. Further studies are needed to decipher the optimal timing and patient selection for this growing practice.

The receptor for advanced glycation endproducts (RAGE) is involved in multiple inflammatory processes. RAGE participates in adaptive and innate immune responses but its role in human immune cell responses has not been directly tested in vivo. We treated humanized mice (NSG) with the small molecule antagonist of RAGE, azeliragon, (AZ), and measured effects on xenogeneic (B6) skin graft rejection. AZ delayed the median time to xenograft rejection (22 vs 56 days, P = 0.0001). PD-1 expression on CD4+ and CD8+ T cells was lower following AZ therapy. Transcriptome studies showed inhibition of pathways in splenocytes with AZ including IL-23, IL-17A and IL-1β signaling. The serum levels of IL-1β and IL-17A in AZ treated mice were reduced in mice that did not reject skin grafts. The RAGE antagonist prevented xenograft rejection by human immune cells in a murine model. A RAGE antagonist may be a useful inhibitor of adaptive human immune responses., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To summarize the evidence and determine the most effective impression technique for implant-supported prostheses in terms of accuracy, time efficiency, and patient preference in partially and completely edentulous arches., Materials and Methods: The searches were performed independently up to April 30, 2021 by two review authors through the Cochrane Oral Health Review, MEDLINE/PubMed, LILACS, and Science Direct databases. Moreover, manual and gray literature searches were performed to identify further potential reviews. Only English language-based systematic reviews with and without meta-analyses evaluating the different dental implant impression techniques were included. The outcomes assessed were accuracy, time efficiency, and patient preference. The methodologic quality of the included reviews was investigated by using the R-AMSTAR tool, and the degree of overlap of primary studies was assessed by calculating the percentage of corrected covered area (CCA) as proposed by Pieper et al. 64 Results: The qualitative analysis included a total of 28 reviews, 8 of which included meta-analyses, published between 2008 and 2021, involving a total of 42 clinical trials and 203 laboratory studies. Digital vs conventional implant impression techniques were compared in 17 reviews, different digital impressions in 3 reviews, and different conventional impression techniques in the remaining reviews. Overall, the methodologic quality assessed by using the R-AMSTAR tool was moderate (mean: 26.7 ± 5.5) with slight overlap of primary studies (CCA; 5.23%)., Conclusion: Within an overall moderate methodologic quality, the digital implant impressions showed favorable outcomes in terms of accuracy, time efficiency, and patient preference in partially edentulous arches involving three or fewer implants. However, the accuracy of full-arch digital impressions involving multiple implants is not satisfactory and needs significant improvements. Hence, future studies following stringent guidelines and robust methodology are recommended to substantiate the findings of this overview and provide a high level of evidence.

Background: Ayurdvedic derived medicines are most promising and effective in the treatment of several cardiovascular diseases. Cocculus hirsutus (CH) has been reported for broad spectrum of activities like anticancer, antidiabetic, antioxidant, cardiotonic and hypotensive etc. OBJECTIVES: The present study aimed to find the cardio-protective effect of CH in experimental hypertension in rats., Materials and Methods: For acute renal hypertension, CH animals were pre-treated with CH-1 (250 mg/kg) and CH-2 (500 mg/kg) p. o. for 14 days. On the 15th day, hypertension was induced by renal occlusion and the mean arterial blood pressure (MABP) was recorded. For CAL pretreatment of CH-1 and CH-2 was given for 7 days on the 8th day animals were operated on for ligation. The MABP and the time of onset of ventricular tachycardia (VT), premature ventricular systole (PVS) were recorded. For induction of hypercholesterolemia, animals were fed with a high cholesterol diet (CD) with CH-1 and CH-2 for 21 days. The antioxidant potential of CH was done using the assay of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx)., Results: CH treatment significantly decreases the MABP, the onset of VT and PVS. The histology show intact cardiac muscle with minimum necrosis and inflammation. CH treatment shows significant decrease in cholesterol, triglycerides, and glucose while HDL levels are significantly increased. The aortic section of CH-treated animals shows the intact layers of the artery, normal thickness and restoration of antioxidant enzymatic activity., Conclusion: The study shows significant cardio protective effect of CH in experimental animals., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Teachers are the backbone of any civilized society as they are the keepers of knowledge, wisdom and values. Lack of infrastructure, manpower and resources makes voice the most important tool for a teacher. Teachers need to speak loudly for long periods often under unfavourable circumstances. Increased vocal effort and incorrect phonation techniques can lead to vocal fold tissue damage and vocal fold pathologies and hence voice problems producing adverse effects on teaching performance. To study the prevalence of voice disorders in Indian female secondary school teacher population. To identify the risk factors for the development of voice disorders. A multicentric, cross-sectional observational study of 200 teachers were conducted in 4 schools over a period of 2 years . Female teachers who gave consent and were willing for follow up were included in the study. Details were collected using a structured questionnaire. Subjective analysis by VHI, perceptual analysis by GRABS score, acoustic analysis and direct visualization using Hopkins 70° rigid laryngoscope were done.The prevalence of voice disorders was 18.5%. Risk factors identified were age group 41-60 years, repeated respiratory allergies, comorbidities, constitutional symptoms, increased number of years of teaching and number of lecture hours per week. VHI, GRABS, Acoustic analysis findings were consistent with Rigid Laryngoscopic finding making them effective tools in the assessment of voice., Competing Interests: Conflict of interestNo conflict of interest during this case report., (© Association of Otolaryngologists of India 2020.)

Introduction: Life on Earth depends on oxygen; human tissues require oxygen signaling, whereas many microorganisms, including bacteria, thrive in anoxic environments. Despite these differences, human tissues and bacteria coexist in close proximity to each other such as in the intestine. How oxygen governs intestinal-bacterial interactions remains poorly understood., Methods: To address to this gap, we created a dual-oxygen environment in a microfluidic device to study the role of oxygen in regulating the regulation of intestinal enzymes and proteins by gut bacteria. Two-layer microfluidic devices were designed using a fluid transport model and fabricated using soft lithography. An oxygen-sensitive material was integrated to determine the oxygen levels. The intestinal cells were cultured in the upper chamber of the device. The cells were differentiated, upon which bacterial strains, a facultative anaerobe, Escherichia coli Nissle 1917, and an obligate anaerobe, Bifidobacterium Adolescentis , were cultured with the intestinal cells., Results: The microfluidic device successfully established a dual-oxygen environment. Of particular importance in our findings was that both strains significantly upregulated mucin proteins and modulated several intestinal transporters and transcription factors but only under the anoxic-oxic oxygen gradient, thus providing evidence of the role of oxygen on bacterial-epithelial signaling., Conclusions: Our work that integrates cell and molecular biology with bioengineering presents a novel strategy to engineer an accessible experimental system to provide tailored oxygenated environments. The work could provide new avenues to study intestine-microbiome signaling and intestinal tissue engineering, as well as a novel perspective on the indirect effects of gut bacteria on tissues including tumors., Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-022-00735-x., Competing Interests: Conflict of interestThe authors Chengyao Wang, Andrea Cancino, Jasmine Baste, Daniel Marten, Advait Anil Joshi, Amreen Nasreen, Abhinav Bhushan have declared that no conflict of interest exists., (© The Author(s) under exclusive licence to Biomedical Engineering Society 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: To evaluate whether the placement of endosseous dental implants along with intentionally retained root fragments enhances peri-implant histologic characteristics and outcomes in healthy animal models., Materials and Methods: Two review authors independently performed electronic literature searches across the PubMed/MEDLINE, LILACS, EBSCOhost, and Science Direct databases by using different keywords and Medical Subject Headings terms to identify relevant articles. Only preclinical animal trials evaluating the histology of peri-implant tissues around endosseous dental implants placed along with intentionally retained root fragments were included in the review. The risk of bias assessment was investigated using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool, and the reporting quality of each trial was evaluated using the Animal Research: Reporting in Vivo Experiments guidelines., Results: Seven preclinical trials including a total of 33 animals and 155 endosseous dental implants were eligible for the analysis. One trial reported the histologic assessment of peri-implant tissues around endosseous dental implants with ankylotic root fragments, whereas the other six studies used nonankylotic root fragments. The effects of the length of retained root fragments on peri-implant tissues were reported in two trials that showed contrasting results. The effects of the width of retained root fragments were assessed in two trials reporting that a remaining thickness < 2 mm and buccal bone thickness > 3 mm favors alveolar bone preservation over a period of 12 weeks. Although the mean quality assessment score for all preclinical trials was moderately high, the summary for the risk of bias presented a high risk., Conclusion: Limited data and short-term preclinical evidence showed optimal peri-implant histologic findings of endosseous dental implants placed along with intentionally retained root fragments. However, further preclinical histologic evaluation with homogenous populations and long-term controlled clinical studies are needed to substantiate its applicability in clinical situations.

Girls with obesity are at increased risk of early puberty. Obesity is associated with insulin resistance and hyperinsulinemia. We hypothesized that insulin plays a physiological role in pubertal transition, and super-imposed hyperinsulinemia due to childhood obesity promotes early initiation of puberty in girls. To isolate the effect of hyperinsulinemia from adiposity, we compared pre-pubertal and pubertal states in hyperinsulinemic, lean muscle (M)-insulin-like growth factor 1 receptor (IGF-1R)-lysine (K)-arginine (R) (MKR) mice to normoinsulinemic WT, with puberty onset defined by vaginal opening (VO). Our results show MKR had greater insulin resistance and higher insulin levels (P < 0.05) than WT despite lower body weight (P < 0.0001) and similar IGF-1 levels (P = NS). Serum luteinizing hormone (LH) levels were higher in hyperinsulinemic MKR (P = 0.005), and insulin stimulation induced an increase in LH levels in WT. VO was earlier in hyperinsulinemic MKR vs WT (P < 0.0001). When compared on the day of VO, kisspeptin expression was higher in hyperinsulinemic MKR vs WT (P < 0.05), and gonadotropin-releasing hormone and insulin receptor isoform expression was similar (P = NS). Despite accelerated VO, MKR had delayed, disordered ovarian follicle and mammary gland development. In conclusion, we found that hyperinsulinemia alone without adiposity triggers earlier puberty. In our study, hyperinsulinemia also promoted dyssynchrony between pubertal initiation and progression, urging future studies in girls with obesity to assess alterations in transition to adulthood.

Objective: Laryngotracheal reconstructive surgery very often requires placement of laryngeal stents, but most of the available stents either do not conform to the shape of the glottis or are open at the upper end, causing significant tissue reaction and aspiration. LT-Mold is an ideal stent in this respect, but it is not readily available., Case Report: The authors of this study fashioned a laryngeal stent out of a readily available Montgomery T-tube in such a way that it had a closed upper end and was well-conformed to the architecture of the larynx. This stent was used in a case of posterior expansion laryngoplasty, and post-operatively the patient had a patent airway with good voice and no aspiration., Conclusion: A customised laryngeal stent is well tolerated and helps to solve complicated cases of posterior glottic stenosis.

Chronic anemia is commonly observed in patients with hemoglobinopathies, mainly represented by disorders of altered hemoglobin (Hb) structure (sickle cell disease, SCD) and impaired Hb synthesis (e.g. thalassemia syndromes, non-SCD anemia). Both hemoglobinopathies have been associated with white matter (WM) alterations. Novel structural MRI research in our laboratory demonstrated that WM volume was diffusely lower in deep, watershed areas proportional to anemia severity. Furthermore, diffusion tensor imaging analysis has provided evidence that WM microstructure is disrupted proportionally to Hb level and oxygen saturation. SCD patients have been widely studied and demonstrate lower fractional anisotropy (FA) in the corticospinal tract and cerebellum across the internal capsule and corpus callosum. In the present study, we compared 19 SCD and 15 non-SCD anemia patients with a wide range of Hb values allowing the characterization of the effects of chronic anemia in isolation of sickle Hb. We performed a tensor analysis to quantify FA changes in WM connectivity in chronic anemic patients. We calculated the volumetric mean of FA along the pathway of tracks connecting two regions of interest defined by BrainSuite's BCI-DNI atlas. In general, we found lower FA values in anemic patients; indicating the loss of coherence in the main diffusion direction that potentially indicates WM injury. We saw a positive correlation between FA and hemoglobin in these same regions, suggesting that decreased WM microstructural integrity FA is highly driven by chronic hypoxia. The only connection that did not follow this pattern was the connectivity within the left middle-inferior temporal gyrus. Interestingly, more reductions in FA were observed in non-SCD patients (mainly along with intrahemispheric WM bundles and watershed areas) than the SCD patients (mainly interhemispheric)., Competing Interests: Author JW is a Consultant for BluebirdBio, Celgene, Apopharma, WorldcareClinical, and BiomeInformatics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 González-Zacarías, Choi, Vu, Xu, Shen, Joshi, Leahy and Wood.)

Human skin equivalents emerged as novel tools in preclinical dermatological research. It is being claimed that they may bridge the translational gap between preclinical and clinical research, yet only a few studies have investigated their suitability for preclinical drug testing so far. Therefore, we investigated if inflammatory skin equivalents, which emulate hallmarks of atopic dermatitis (AD), are suitable to assess the anti-inflammatory effects of dexamethasone (DXM) in a cream formulation or loaded onto dendritic core-multishell nanoparticles. Topical DXM application resulted in significantly decreased expression of the proinflammatory cytokine TSLP, increased expression of the skin barrier protein involucrin, and facilitated glucocorticoid receptor translocation in a dose-dependent manner. Further, DXM treatment inhibited gene expression of extracellular matrix components, potentially indicative of the known skin atrophy-inducing side effects of glucocorticoids. Overall, we were able to successfully assess the anti-inflammatory effects of DXM and the superiority of the nanoparticle formulation. Nevertheless the identification of robust readout parameters proved challenging and requires careful study design.

We present a new high-quality, single-subject atlas with sub-millimeter voxel resolution, high SNR, and excellent gray-white tissue contrast to resolve fine anatomical details. The atlas is labeled into two parcellation schemes: 1) the anatomical BCI-DNI atlas, which is manually labeled based on known morphological and anatomical features, and 2) the hybrid USCBrain atlas, which incorporates functional information to guide the sub-parcellation of cerebral cortex. In both cases, we provide consistent volumetric and cortical surface-based parcellation and labeling. The intended use of the atlas is as a reference template for structural coregistration and labeling of individual brains. A single-subject T1-weighted image was acquired five times at a resolution of 0.547 mm × 0.547 mm × 0.800 mm and averaged. Images were processed by an expert neuroanatomist using semi-automated methods in BrainSuite to extract the brain, classify tissue-types, and render anatomical surfaces. Sixty-six cortical and 29 noncortical regions were manually labeled to generate the BCI-DNI atlas. The cortical regions were further sub-parcellated into 130 cortical regions based on multi-subject connectivity analysis using resting fMRI (rfMRI) data from the Human Connectome Project (HCP) database to produce the USCBrain atlas. In addition, we provide a delineation between sulcal valleys and gyral crowns, which offer an additional set of 26 sulcal subregions per hemisphere. Lastly, a probabilistic map is provided to give users a quantitative measure of reliability for each gyral subdivision. Utility of the atlas was assessed by computing Adjusted Rand Indices (ARIs) between individual sub-parcellations obtained through structural-only coregistration to the USCBrain atlas and sub-parcellations obtained directly from each subject's resting fMRI data. Both atlas parcellations can be used with the BrainSuite, FreeSurfer, and FSL software packages., (Copyright © 2022. Published by Elsevier B.V.)

Species distribution data are an essential biodiversity variable requiring robust monitoring to inform wildlife conservation. Yet, such data remain inherently sparse because of the logistical challenges of monitoring biodiversity across broad geographic extents. Surveys of people knowledgeable about the occurrence of wildlife provide an opportunity to evaluate species distributions and the ecology of wildlife communities across large spatial scales. We analyzed detection histories of 30 vertebrate species across the Western Ghats biodiversity hotspot in India, obtained from a large-scale interview survey of 2318 people who live and work in the forests of this region. We developed a multispecies occupancy model that simultaneously corrected for false-negative (non-detection) and false-positive (misidentification) errors that interview surveys can be prone to. Using this model, we integrated data across species in composite analyses of the responses of functional species groups (based on disturbance tolerance, diet, and body mass traits) to spatial variation in environmental variables, protection, and anthropogenic pressures. We observed a positive association between forest cover and the occurrence of species with low tolerance of human disturbance. Protected areas were associated with higher occurrence for species across different functional groups compared with unprotected lands. We also observed the occurrence of species with low disturbance tolerance, herbivores, and large-bodied species was negatively associated with developmental pressures, such as human settlements, energy production and mining, and demographic pressures, such as biological resource extraction. For the conservation of threatened vertebrates, our work underscores the importance of maintaining forest cover and reducing deforestation within and outside protected areas, respectively. In addition, mitigating a suite of pervasive human pressures is also crucial for wildlife conservation in one of the world's most densely populated biodiversity hotspots., (© 2021 Society for Conservation Biology.)

Background and Purpose: Although posttraumatic epilepsy is a common complication of traumatic brain injury, the relationship between these conditions is unclear and early posttraumatic epilepsy detection and prevention remain major unmet clinical challenges. This study aimed to identify imaging biomarkers that predict posttraumatic epilepsy among survivors of traumatic brain injury on the basis of an MR imaging data set., Materials and Methods: We performed tensor-based morphometry to analyze brain-shape changes associated with traumatic brain injury and to derive imaging features for statistical group comparison. Additionally, machine learning was used to identify structural anomalies associated with brain lesions. Automatically generated brain lesion maps were used to identify brain regions where lesion load may indicate an increased incidence of posttraumatic epilepsy. We used 138 non-posttraumatic epilepsy subjects for training the machine learning method. Validation of lesion delineation was performed on 15 subjects. Group analysis of the relationship between traumatic brain injury and posttraumatic epilepsy was performed on an independent set of 74 subjects (37 subjects with and 37 randomly selected subjects without epilepsy)., Results: We observed significant F -statistics related to tensor-based morphometry analysis at voxels close to the pial surface, which may indicate group differences in the locations of edema, hematoma, or hemorrhage. The results of the F -test on lesion data showed significant differences between groups in both the left and right temporal lobes. We also saw significant differences in the right occipital lobe and cerebellum., Conclusions: Statistical analysis suggests that lesions in the temporal lobes, cerebellum, and the right occipital lobe are associated with an increased posttraumatic epilepsy incidence., (© 2022 by American Journal of Neuroradiology.)

The presence of outliers can severely degrade learned representations and performance of deep learning methods and hence disproportionately affect the training process, leading to incorrect conclusions about the data. For example, anomaly detection using deep generative models is typically only possible when similar anomalies (or outliers) are not present in the training data. Here we focus on variational autoencoders (VAEs). While the VAE is a popular framework for anomaly detection tasks, we observe that the VAE is unable to detect outliers when the training data contains anomalies that have the same distribution as those in test data. In this paper we focus on robustness to outliers in training data in VAE settings using concepts from robust statistics. We propose a variational lower bound that leads to a robust VAE model that has the same computational complexity as the standard VAE and contains a single automatically-adjusted tuning parameter to control the degree of robustness. We present mathematical formulations for robust variational autoencoders (RVAEs) for Bernoulli, Gaussian and categorical variables. The RVAE model is based on beta-divergence rather than the standard Kullback-Leibler (KL) divergence. We demonstrate the performance of our proposed β -divergence-based autoencoder for a variety of image and categorical datasets showing improved robustness to outliers both qualitatively and quantitatively. We also illustrate the use of our robust VAE for detection of lesions in brain images, formulated as an anomaly detection task. Finally, we suggest a method to tune the hyperparameter of RVAE which makes our model completely unsupervised., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Polymeric nanogels are promising nonirritating nanocarriers for topical delivery applications. However, conventional hydrophilic networks limit encapsulation of hydrophobic therapeutics and hinder tailored interactions with the amphiphilic skin barrier. To address these limitations, we present amphiphilic nanogels containing hydrophilic networks with hydrophobic domains. Two competing factors determine favorable nanogel-skin interactions and need to be balanced through network composition: suitable surface hydrophobicity and low network rigidity (through physical hydrophobic cross-links). To ensure comparability in such investigations, we prepared a library of nanogels with increasing hydrophobic cholesteryl amounts but similar colloidal features. By combining mechanical and surface hydrophobicity tests (atomic force microscopy (AFM)) with dermal delivery experiments on excised human skin, we can correlate an increased delivery efficacy of Nile red to the viable epidermis with a specific network composition, i.e., 20-30 mol % cholesterol. Thus, our nanogel library identifies a specific balance between surface amphiphilicity and network rigidity to guide developments of advanced dermal delivery vehicles.

Statement of Problem: Osseodensification, a counterclockwise drilling technique for the placement of endosseous implants is a popular clinical technique. However, the effect of the osseodensification technique on primary implant stability, bone-implant contact, and bone area frequency occupancy is unclear., Purpose: The purpose of this systematic review and meta-analysis was to investigate the biomechanical and histomorphometric outcomes of endosteal implants placed by using the osseodensification technique in animal models., Material and Methods: An electronic search through Medline/PubMed, Lilacs, and Science Direct databases, and an additional manual search of the reference list of included articles was conducted by using specific keywords and Medical Subject Headings (MeSH) terms for articles in the English language and published up to April 31, 2020. Only animal studies comparing the biomechanical and histomorphometric outcomes of endosteal implants placed by using the osseodensification and conventional drilling protocol were included. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) tool was used to determine the risk of bias assessment, and the quality of included studies was assessed by using Animal Research: Reporting in Vivo Experiments (ARRIVE) guidelines., Results: Nine studies were included. The results of the meta-analysis showed that the pooled weighted mean difference of the insertion torque value for the primary implant stability of endosseous dental implants placed by using the osseodensification technique was 2.270 (95% confidence interval [CI]=1.147 to 3.393; P<.001), the weighted mean difference of the percentage of bone-implant contact at 3 weeks was 0.487 (95% CI=0.220 to 0.754; P=.114), the weighted mean difference of the percentage of bone-implant contact at 6 weeks was 0.565 (95% CI=0.219 to 0.911; P=.448), the weighted mean difference of the percentage of bone area frequency occupancy at 3 weeks was 0.679 (95% CI=0.265 to 1.093; P=.073), and the weighted mean difference of the percentage of bone area frequency occupancy at 6 weeks was 0.391 (95% CI=-0.204 to 0.986; P=.027)., Conclusions: Limited data from animal studies suggest that the primary implant stability, bone-implant contact, and bone area frequency occupancy significantly improved for the endosteal implants placed by using the osseodensification technique compared with conventional drilling protocol. However, additional laboratory and clinical studies are recommended to provide stronger evidence., (Copyright © 2020 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Background: The conventional approach for the development of any pharmaceutically active molecule is a time-consuming and costly process because the synthesis is followed by laboratory tests which are then followed by long clinical trials. Hence, a faster approach is desired. This article discusses Ethambutol, a frontline anti-tubercular drug that has its properties predicted by the SwissADME tool and the results would be compared with the findings published in the literature., Objective: The main objective is to study the predicted and experimental ADME properties, compare them and study the predicted targets and understand the use of SwissADME for designing other drug molecules., Methods: SwissADME, an online tool for ADME prediction, was used along with Swiss Target Prediction to understand the targets of the drug. Further, experimental data was obtained from the available scientific literature., Results: We found certain similarities between the predicted and experimental data. However, there were some variations, depending on the testing conditions. The results are interpreted ahead in the article., Conclusion: Ethambutol's predicted ADME properties are discussed and as per findings from results, it can be concluded that other drug molecules can be similarly predicted using these tools. Also, based on predicted data, we can reformulate and prepare some different preparations of the drug., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: To summarize the methodologic quality and outcome measures from systematic reviews and meta-analyses evaluating the efficacy of different nonsurgical therapies for the treatment of peri-implant diseases., Materials and Methods: Two review authors independently searched for systematic reviews and meta-analyses evaluating the efficacy of different nonsurgical therapies for treatment of peri-implant diseases in three different databases: MEDLINE, Embase, and the Cochrane Library. In addition, journals with a high impact factor in the fields of periodontics, prosthodontics, oral maxillofacial surgery, and implant dentistry were analyzed for potential reviews. The search was implemented from January 2010 through August 2020. Eligible reviews were screened and assessed to determine the characteristics and outcome measures. Furthermore, two review authors independently evaluated the methodologic quality by using the AMSTAR tool and the checklist proposed by Glenny et al. The interrater agreement was assessed by using the Cohen kappa coefficient. The assessment of correlation between the findings of the AMSTAR tool and Glenny et al checklist was performed by using the Spearman correlation., Results: Fifteen systematic reviews and 12 meta-analyses were evaluated based on the inclusion criteria. One review investigated the efficacy of growth factors and another investigated glycine powder air polishing, 5 evaluated the role of antimicrobial photodynamic therapy, 8 assessed the effect of laser therapy, and 13 compared the different nonsurgical therapies with the surgical therapies for the treatment of peri-implant diseases. The quality assessment score evaluated by the AMSTAR checklist ranged from 5 to 11 with a mean of 7.5 ± 1.8, whereas the score evaluated by the Glenny et al checklist ranged from 3 to 14 with a mean of 9.7 ± 2.8. Spearman correlation analysis between these two tools reported a high correlation (r = 0.91) that was statistically significant (P < .001)., Conclusion: The summarized evidence of this overview shows that the different nonsurgical therapies are effective for the treatment of peri-implant mucositis. The lack of sufficient long-term data involving large datasets results in their inconclusive efficacy in the treatment of peri-implantitis. However, the summary is determined from the moderate quality of evidence. Hence, future well-designed high-quality trials are encouraged to reassess the findings.

Despite impressive state-of-the-art performance on a wide variety of machine learning tasks in multiple applications, deep learning methods can produce over-confident predictions, particularly with limited training data. Therefore, quantifying uncertainty is particularly important in critical applications such as lesion detection and clinical diagnosis, where a realistic assessment of uncertainty is essential in determining surgical margins, disease status and appropriate treatment. In this work, we propose a novel approach that uses quantile regression for quantifying aleatoric uncertainty in both supervised and unsupervised lesion detection problems. The resulting confidence intervals can be used for lesion detection and segmentation. In the unsupervised setting, we combine quantile regression with the Variational AutoEncoder (VAE). The VAE is trained on lesion-free data, so when presented with an image with a lesion, it tends to reconstruct a lesion-free version of the image. To detect the lesion, we then compare the input (lesion) and output (lesion-free) images. Here we address the problem of quantifying uncertainty in the images that are reconstructed by the VAE as the basis for principled outlier or lesion detection. The VAE models the output as a conditionally independent Gaussian characterized by its mean and variance. Unfortunately, joint optimization of both mean and variance in the VAE leads to the well-known problem of shrinkage or underestimation of variance. Here we describe an alternative Quantile-Regression VAE (QR-VAE) that avoids this variance shrinkage problem by directly estimating conditional quantiles for the input image. Using the estimated quantiles, we compute the conditional mean and variance for the input image from which we then detect outliers by thresholding at a false-discovery-rate corrected p-value. In the supervised setting, we develop binary quantile regression (BQR) for the supervised lesion segmentation task. We show how BQR can be used to capture uncertainty in lesion boundaries in a manner that characterizes expert disagreement.

Statement of Problem: The performance of the autogenous bone ring (ABR) technique used for the vertical bone augmentation procedure has not yet been determined., Purpose: The purpose of this systematic review was to investigate whether the ABR technique for the vertical bone augmentation procedure with simultaneous implant placement enhances the histologic and histomorphometric outcomes in surgically created bone defects in animal models., Material and Methods: An electronic search of 3 databases, Medline/PubMed, Science Direct, Lilacs, and a manual search of a reference list of relevant studies were performed. Only animal studies regarding vertical bone augmentation by using the ABR technique with simultaneous implant placement in surgically created bone defects were included in the review. The SYstematic Review Center for Laboratory Animal Experimentation tool was used to determine the risk of bias assessment, and the quality of included studies was assessed by using the Animal Research: Reporting in Vivo Experiments guidelines., Results: Five studies were included in the qualitative analysis based on the inclusion and exclusion criteria. One study comparing the ABR technique with the bovine and biphasic ring reported a high percentage of bone area and bone implant contact of the ABR at 5 weeks of osseointegration. Similar histologic findings were reported in another study at 4 months of healing, but contrasting data were reported at 8 months. Another study reported an increase in the percentage of bone area and bone implant contact of the ABR technique from 3 months to 6 months of osseointegration. Two studies reported an increase in the percentage of bone area, and 1 study reported a decrease in the mean of bone implant contact, both with simultaneous and staged implant procedures., Conclusion: Based on the limited available studies, the use of the ABR technique for the vertical bone augmentation procedure with simultaneous implant placement presented optimal histologic and histomorphometric outcomes in surgically created bone defects in animal models. However, the results of the current review are not sufficiently robust to support the use of the ABR technique for vertical bone augmentation in humans., (Copyright © 2020 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

We explored the utility of the real-time FLIPR Membrane Potential (FMP) assay as a method to assess kappa opioid receptor (KOR)-induced hyperpolarization. The FMP Blue dye was used to measure fluorescent signals reflecting changes in membrane potential in KOR expressing CHO (CHO-KOR) cells. Treatment of CHO-KOR cells with kappa agonists U50,488 or dynorphin [Dyn (1-13)NH 2 ] produced rapid and concentration-dependent decreases in FMP Blue fluorescence reflecting membrane hyperpolarization. Both the nonselective opioid antagonist naloxone and the κ-selective antagonists nor-binaltorphimine (nor-BNI) and zyklophin produced rightward shifts in the U50,488 concentration-response curves, consistent with competitive antagonism of the KOR mediated response. The decrease in fluorescent emission produced by U50,488 was blocked by overnight pertussis toxin pretreatment, indicating the requirement for PTX-sensitive G proteins in the KOR mediated response. We directly compared the potency of U50,488 and Dyn (1-13)NH 2 in the FMP and [ 35 S]GTPγS binding assays, and found that both were approximately 10 times more potent in the cellular fluorescence assay. The maximum responses of both U50,488 and Dyn (1-13)NH 2 declined following repeated additions, reflecting receptor desensitization. We assessed the efficacy and potency of structurally distinct KOR small molecule and peptide ligands. The FMP assay reliably detected both partial agonists and stereoselectivity. Using KOR-selective peptides with varying efficacies, we found that the FMP assay allowed high throughput quantification of peptide efficacy. These data demonstrate that the FMP assay is a sensitive method for assessing κ-opioid receptor induced hyperpolarization, and represents a useful approach for quantification of potency, efficacy and desensitization of KOR ligands., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Stereotactic electroencephalography (SEEG) has been widely used to explore the epileptic network and localize the epileptic zone in patients with medically intractable epilepsy. Accurate anatomical labeling of SEEG electrode contacts is critically important for correctly interpreting epileptic activity. We present a method for automatically assigning anatomical labels to SEEG electrode contacts using a 3D-segmented cortex and coregistered postoperative CT images., Method: Stereotactic electroencephalography electrode contacts were spatially localized relative to the brain volume using a standard clinical procedure. Each contact was then assigned an anatomical label by clinical epilepsy fellows. Separately, each contact was automatically labeled by coregistering the subject's MRI to the USCBrain atlas using the BrainSuite software and assigning labels from the atlas based on contact locations. The results of both labeling methods were then compared, and a subsequent vetting of the anatomical labels was performed by expert review., Results: Anatomical labeling agreement between the two methods for over 17 000 SEEG contacts was 82%. This agreement was consistent in patients with and without previous surgery (P = .852). Expert review of contacts in disagreement between the two methods resulted in agreement with the atlas based over manual labels in 48% of cases, agreement with manual over atlas-based labels in 36% of cases, and disagreement with both methods in 16% of cases. Labels deemed incorrect by the expert review were then categorized as either in a region directly adjacent to the correct label or as a gross error, revealing a lower likelihood of gross error from the automated method., Significance: The method for semi-automated atlas-based anatomical labeling we describe here demonstrates potential to assist clinical workflow by reducing both analysis time and the likelihood of gross anatomical error. Additionally, it provides a convenient means of intersubject analysis by standardizing the anatomical labels applied to SEEG contact locations across subjects., (© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)