bluuebunny/crossref_metadata_2025 huggingface dataset:
Advantages and Disadvantages of Using Small and Large Animals in Burn Research: Proceedings of the 2021 Research Special Interest Group
Authors: Burmeister David M , Supp Dorothy M , Clark Richard A , Tredget Edward E , Powell Heather M , Enkhbaatar Perenlei , Bohannon Julia K , Cancio Leopoldo C , Hill David M , Nygaard Rachel M
Published: July 2022

Multiple animal species and approaches have been used for modeling different aspects of burn care, with some strategies considered more appropriate or translatable than others. On April 15, 2021, the Research Special Interest Group of the American Burn Association held a virtual session as part of the agenda for the annual meeting. The session was set up as a pro/con debate on the use of small versus large animals for application to four important aspects of burn pathophysiology: burn healing/conversion, scarring, inhalation injury, and sepsis. For each of these topics, two experienced investigators (one each for small and large animal models) described the advantages and disadvantages of using these preclinical models. The use of swine as a large animal model was a common theme due to anatomic similarities with human skin. The exception to this was a well-defined ovine model of inhalation injury; both of these species have larger airways which allow for incorporation of clinical tools such as bronchoscopes. However, these models are expensive and demanding from labor and resource standpoints. Various strategies have been implemented to make the more inexpensive rodent models appropriate for answering specific questions of interest in burns. Moreover, modeling burn-sepsis in large animals has proven difficult. It was agreed that the use of both small and large animal models has merit for answering basic questions about the responses to burn injury. Expert opinion and the ensuing lively conversations are summarized herein, which we hope will help inform experimental design of future research.
Reference Genome of the California Sheephead,Semicossyphus pulcher(Labridae, Perciformes), A Keystone Fish Predator in Kelp Forest Ecosystems
Authors: Bernardi Giacomo , DeBiasse Melissa , Escalona Merly , Marimuthu Mohan P A , Nguyen Oanh , Sacco Samuel , Beraut Eric , Miller Courtney , Toffelmier Erin , Shaffer H Bradley
Published: July 2022

Keystone species are known to play a critical role in kelp forest health, including the well-known killer whales, sea otter, sea urchin, kelp trophic cascade in the Aleutian Islands, Alaska, USA. In California, a major player in the regulation of sea urchin abundance, and in turn, the health of kelp forests ecosystems, is a large wrasse, the California Sheephead, Semicossyphus pulcher. We present a reference genome for this ecologically important species that will serve as a key resource for future conservation research of California’s inshore marine environment utilizing genomic tools to address changes in life-history traits, dispersal, range shifts, and ecological interactions among members of the kelp forest ecological assemblages. Our genome assembly of S. pulcher has a total length of 0.794 Gb, which is similar to many other marine fishes. The assembly is largely contiguous (N50 = 31.9 Mb) and nearly complete (BUSCO single-copy core gene content = 98.1%). Within the context of the California Conservation Genomics Project (CCGP), the genome of S. pulcher will be used as an important reference resource for ongoing whole genome resequencing efforts of the species.
Compact laboratory-based X-ray microscope enabling nondestructive 3D structure acquisition of mouse nephron with high speed and better user accessibility
Authors: Kunishima Naoki , Takeda Yoshihiro , Hirose Raita , Kume Satoshi , Maeda Mitsuyo , Oguchi Akiko , Yanagita Motoko , Shibuya Hirotoshi , Tamura Masaru , Kataoka Yosky , Murakawa Yasuhiro , Ito Koichiro , Omote Kazuhiko
Published: July 2022

X-ray microscopes adopting computed tomography enable nondestructive 3D visualization of biological specimens at micron-level resolution without conventional 2D serial sectioning that is a destructive/laborious method and is routinely used for analyzing renal biopsy in clinical diagnosis of kidney diseases. Here we applied a compact commercial system of laboratory-based X-ray microscope to observe a resin-embedded osmium-stained 1-mm strip of a mouse kidney piece as a model of renal biopsy, toward a more efficient diagnosis of kidney diseases. A reconstructed computed tomography image from several hours of data collection using CCD detector allowed us to unambiguously segment a single nephron connected to a renal corpuscle, which was consistent with previous reports using serial sectioning. Histogram analysis on the segmented nephron confirmed that the proximal and distal tubules were distinguishable on the basis of their X-ray opacities. A 3D rendering model of the segmented nephron visualized a convoluted structure of renal tubules neighboring the renal corpuscle and a branched structure of efferent arterioles. Furthermore, another data collection using scientific complementary metal-oxide semiconductor detector with a much shorter data acquisition time of 15 min provided similar results from the same samples. These results suggest a potential application of the compact laboratory-based X-ray microscope to analyze mouse renal biopsy.
User Involvement as a Catalyst for Collaborative Public Service Innovation
Authors: Callens Chesney
Published: July 2022

Innovation in public services is propelled by collaborations between public actors, private actors, and service users. A substantial literature has centered on the benefits of user involvement in public services, but how user involvement can stimulate collaborative innovation is still largely unknown. This article develops and tests a theoretical framework based on the combined effect of (1) the empowerment of users, (2) specialized knowledge of the users, and (3) the absence of hindering rules and procedures. Data from 19 public–private eHealth collaborations in five European countries, collected through 132 interviews and 124 surveys, are analyzed through fuzzy-set qualitative comparative analysis, and the results indicate that innovation in these partnerships is influenced by the combined effect of these conditions, but that this combined effect is also contingent on the roles the users adopt in the innovation process.
The Case for Medicine-Pediatrics Training in the U.S. Military
Authors: Maciuba Joseph M , Jenkins Mary C
Published: July 2022

Residency programs in the combined specialty of Internal Medicine-Pediatrics (Med-Peds) are not offered in the military graduate medical education system despite existing in the civilian sector for over 50 years. This residency consists of 4 years of training and results in the development of board-certified internists and pediatricians who can care for patients from infancy to death. This versatility, combined with an emphasis on the transition from childhood to adulthood, would be valuable to the Military Health System. Med-Peds physicians could serve in a variety of settings depending on the needs of the military: in the outpatient clinic, in the hospital, or in an operational setting. Specifically, Med-Peds doctors could operate as critical care extenders in austere or operational environments to patients of all ages. This could improve outcomes of pediatric casualties in war because of specific training in both medical and pediatric intensive care units. Med-Peds physicians would integrate seamlessly into the Military Health System to work alongside family medicine doctors, internists, and pediatricians to provide high-quality primary care to service members; this may also allow for the increased flexibility of the medical corps. As there are already military residency programs in pediatrics and internal medicine, the required infrastructure for such a training program exists. The addition of this residency may also lead to more interest in military medicine from prospective applicants to medical school. This essay uses personal experience to explain how the addition of this specialty to the military would benefit the medical mission domestically and abroad.
From the Defense Health Board: Military Accessions and the Continuum of Mental Health Research
Authors: Zebrowski Catherine A , Schaettle Paul R , Alemagno Sonia A , McCaw Brigid R , Valadka Alex B , Sharfstein Steven S , Reid-Arndt Stephanie A , Gorman Gregory H , Lazarus Jeremy A
Published: July 2022

The Defense Health Board conducted a year-long examination of mental health accession screening and related issues. In its August 2020 report, Examination of Mental Health Accession Screening: Predictive Value of Current Measures and Processes, the Board recommends a paradigm shift in how mental health impacts on readiness are understood and addressed. This shift can only occur with the development and implementation of a research plan that follows cohorts of military personnel from recruitment through their military career. The following article describes this research plan as an excerpt of the larger report.
Warthog Genomes Resolve an Evolutionary Conundrum and Reveal Introgression of Disease Resistance Genes
Authors: Garcia-Erill Genís , Jørgensen Christian H F , Muwanika Vincent B , Wang Xi , Rasmussen Malthe S , de Jong Yvonne A , Gaubert Philippe , Olayemi Ayodeji , Salmona Jordi , Butynski Thomas M , Bertola Laura D , Siegismund Hans R , Albrechtsen Anders , Heller Rasmus
Published: July 2022

African wild pigs have a contentious evolutionary and biogeographic history. Until recently, desert warthog (Phacochoerus aethiopicus) and common warthog (P. africanus) were considered a single species. Molecular evidence surprisingly suggested they diverged at least 4.4 million years ago, and possibly outside of Africa. We sequenced the first whole-genomes of four desert warthogs and 35 common warthogs from throughout their range. We show that these two species diverged much later than previously estimated, 400,000–1,700,000 years ago depending on assumptions of gene flow. This brings it into agreement with the paleontological record. We found that the common warthog originated in western Africa and subsequently colonized eastern and southern Africa. During this range expansion, the common warthog interbred with the desert warthog, presumably in eastern Africa, underlining this region’s importance in African biogeography. We found that immune system–related genes may have adaptively introgressed into common warthogs, indicating that resistance to novel diseases was one of the most potent drivers of evolution as common warthogs expanded their range. Hence, we solve some of the key controversies surrounding warthog evolution and reveal a complex evolutionary history involving range expansion, introgression, and adaptation to new diseases.
Exposure to Cigarette Smoke Impedes Human Osteoblast Differentiation Independently of Nicotine
Authors: Martinez Ivann K C , Sparks Nicole R L , Madrid J V , Talbot Prue , zur Nieden Nicole I
Published: July 2022

Introduction

Tobacco smoking has been implicated in an array of adverse health outcomes, including those that affect adult bone. However, little is known about the impact of tobacco products on developing bone tissue as it develops in the embryo.

Aims and Methods

Here, human embryonic stem cells were differentiated into osteoblasts in vitro and concomitantly exposed to various concentrations of smoke solutions from two conventional, one additive-free and two harm-reduction brands of cigarettes. Differentiation inhibition was determined by calcium assays that quantified matrix mineralization and compared to the cytotoxicity of the tobacco product.

Results

Exposure to mainstream smoke from conventional and additive-free cigarettes caused no inhibition of cell viability or mineralization, while sidestream smoke (SS) concentration-dependently produced cell death. In contrast, mineralization was inhibited only by the highest mainstream concentration of harm-reduction smoke solution. Additionally, sidestream smoke solution from the harm-reduction cigarettes impeded calcification at concentrations lower than those determined to be cytotoxic for conventional products.

Conclusions

Sidestream smoke impaired in vitro osteogenesis at subtoxic concentrations. In addition, though often perceived as safer, smoke from harm-reduction cigarettes was more potent in inhibiting in vitro osteogenesis than smoke from conventional cigarettes.

Implications

This study adds to a growing list of adverse outcomes associated with pre-natal tobacco exposure. Specifically, in vitro exposure to tobacco products interfered with osteogenic differentiation of human embryonic stem cells, a well-established surrogate model for human embryonic bone development. Contrasting a diverse array of tobacco products unveiled that sidestream smoke was generally more developmentally osteotoxic than mainstream smoke and that harm-reduction products may not be less harmful than conventional products, adverse effects that were seemingly independent of nicotine.
The Impact of the COVID-19 Pandemic on Tobacco Treatment Program Implementation at National Cancer Institute-Designated Cancer Centers
Authors: Hohl Sarah D , Shoenbill Kimberly A , Taylor Kathryn L , Minion Mara , Bates-Pappas Gleneara E , Hayes Rashelle B , Nolan Margaret B , Simmons Vani N , Steinberg Michael B , Park Elyse R , Ashing Kimlin , Beneventi Diane , Sanderson Cox Lisa , Goldstein Adam O , King Andrea , Kotsen Chris , Presant Cary A , Sherman Scott E , Sheffer Christine E , Warren Graham W , Adsit Robert T , Bird Jennifer E , D’Angelo Heather , Fiore Michael C , Van Thanh Nguyen Claire , Pauk Danielle , Rolland Betsy , Rigotti Nancy A
Published: July 2022

Introduction

The COVID-19 pandemic disrupted cancer screening and treatment delivery, but COVID-19’s impact on tobacco cessation treatment for cancer patients who smoke has not been widely explored.

Aims and Methods

We conducted a sequential cross-sectional analysis of data collected from 34 National Cancer Institute (NCI)-designated cancer centers participating in NCI’s Cancer Center Cessation Initiative (C3I), across three reporting periods: one prior to COVID-19 (January–June 2019) and two during the pandemic (January–June 2020, January–June 2021). Using McNemar’s Test of Homogeneity, we assessed changes in services offered and implementation activities over time.

Results

The proportion of centers offering remote treatment services increased each year for Quitline referrals (56%, 68%, and 91%; p = .000), telephone counseling (59%, 79%, and 94%; p = .002), and referrals to Smokefree TXT (27%, 47%, and 56%; p = .006). Centers offering video-based counseling increased from 2020 to 2021 (18% to 59%; p = .006), Fewer than 10% of centers reported laying off tobacco treatment staff. Compared to early 2020, in 2021 C3I centers reported improvements in their ability to maintain staff and clinician morale, refer to external treatment services, train providers to deliver tobacco treatment, and modify clinical workflows.

Conclusions

The COVID-19 pandemic necessitated a rapid transition to new telehealth program delivery of tobacco treatment for patients with cancer. C3I cancer centers adjusted rapidly to challenges presented by the pandemic, with improvements reported in staff morale and ability to train providers, refer patients to tobacco treatment, and modify clinical workflows. These factors enabled C3I centers to sustain evidence-based tobacco treatment implementation during and beyond the COVID-19 pandemic.

Implications

This work describes how NCI-designated cancer centers participating in the Cancer Center Cessation Initiative (C3I) adapted to challenges to sustain evidence-based tobacco use treatment programs during the COVID-19 pandemic. This work offers a model for resilience and rapid transition to remote tobacco treatment services delivery and proposes a policy and research agenda for telehealth services as an approach to sustaining evidence-based tobacco treatment programs.
Beyond “Exercise as Medicine” in Physical Therapy: Toward the Promotion of Exercise as a Public Good
Authors: Davenport Todd E , Griech Sean F , Deamer Kathryn E , Gale Lewis R
Published: July 2022

Physical therapists are uniquely positioned through their knowledge and skills to help people become more physically active, which may reduce the consequences of physical inactivity for health-related quality of life and the global economy. The “Exercise Is Medicine” campaign was introduced in 2007. It holds that exercise may be prescribed like a medicine. Although this analogy doubtlessly has promoted innumerable life-changing conversations between clinicians and patients, there are important shortcomings to considering physical activity and exercise as medicine. In the United States, many of these shortcomings relate to how medical services are provided and remunerated. Medical care is provided in the context of exclusive groups, which are established by insurance, preferred service populations, or other characteristics that determine a basis for providing care. Exclusivity means that medical care is frequently provided in a type of club. The club structure of medical care jeopardizes the ability of nonmembers to benefit. Medical care clubs based on payment create an environment in which nonpaying customers may not benefit in the same manner as paying customers from approaches that consider exercise prescribed as medicine. This clinical perspective reviews the characteristics of exercise as a good, focusing on how it is prescribed by physical therapists. It discusses how physical therapists may become involved in the process of making exercise a public good by reducing its exclusivity. Multiple levels of involvement are recommended at the societal, community, and individual levels. These involvements may be guided by an existing construct proposed by the World Health Organization, which would bring the global physical therapy profession into a common alignment. This Perspective concludes with a discussion that anticipates the shortcomings of conceptualizing exercise as a public good to be addressed in future service delivery models.
Soybean Cyst Nematode of Soybean: A Diagnostic Guide
Authors: Mahecha-Garnica Sofia , Ye Weimin , Schumacher Lesley A. , Gorny Adrienne M.
Published: July 2022

The soybean cyst nematode (SCN; Heterodera glycines Ichinohe 1952) is one of the most economically important pathogens of soybean. The species impacts soybean production worldwide and causes significant yield loss even in the absence of visible aboveground symptoms. This diagnostic guide describes the host range, signs, symptoms, and geographic distribution of SCN, and includes information regarding pathogen identification, storage, and pathogenicity tests for this nematode.
Transcriptome Profiling Reveals Molecular Players in Early Soybean–Sclerotinia sclerotiorum Interaction
Authors: Wei Wei , Wu Xing , Blahut-Beatty Laureen , Simmonds Daina H. , Clough Steven J.
Published: July 2022

Sclerotinia sclerotiorum causes Sclerotinia stem rot on soybean. Using RNA sequencing, the transcriptomes of the soybean host and the S. sclerotiorum pathogen were simultaneously determined at 4 and 8 h postinoculation (hpi). Two soybean genotypes were involved: a resistant oxalate oxidase (OxO)-transgenic line and its susceptible parent, AC Colibri (AC). Of the 594 genes that were significantly induced by S. sclerotiorum, both hosts expressed genes related to jasmonic acid, ethylene, oxidative burst, and phenylpropanoids. In all, 36% of the differentially expressed genes encoded genes associated with transcription factors, ubiquitination, or general signaling transduction such as receptor-like kinases, mitogen-activated protein kinase kinases, and hormones. No significant differentially expressed genes were identified between genotypes, suggesting that oxalic acid (OA) did not play a differential role in early disease development or primary lesion formation under the conditions used. Looking at pathogen behavior through its gene expression during infection, thousands of genes in S. sclerotiorum were induced at 8 hpi, compared with expression in culture. Many plant cell-wall-degrading enzymes (PCWDEs), sugar transport genes, and genes involved in secondary metabolism were upregulated and could contribute to early pathogenesis. When infecting the OxO plants, there was a higher induction of genes encoding OA, botcinic acid, PCWDEs, proteases, and potential effectors, revealing the wealth of virulence factors available to this pathogen as it attempts to colonize a host. Data presented identify hundreds of genes associated with the very early stages of infection for both the host and pathogen.
LNIT-Local nasal immunotherapy in allergic rhinitis: revisited evidence and perspectives
Authors: Kanjanawasee Dichapong , Tantilipikorn Pongsakorn
Published: July 2022

Purpose of review

Allergen immunotherapy (AIT) is a personalized treatment approach for the allergic airway disease. The most common routes of administration are subcutaneous and sublingual. Local nasal immunotherapy (LNIT) presents another alternative route for allergen desensitization. Nasal mucosa is the first entry site of pathogens and numerous lymphoid organs are located in this area, making LNIT a favorable method for triggering immune tolerance. LNIT has shown promising results in reducing symptoms and medication use in allergic rhinitis patients. Over time, difficulties in dosing adjustments have made this method less popular. Recent advances in intranasal drug delivery systems warrant re-examination of LNIT as a viable option for the treatment of the allergic airway disease.

Recent findings

The scope of the review includes evidences of LNIT in human trials including comparison with placebo and conventional method of immunotherapy. Recent articles regarding the mechanism of LNIT and the challenges of intranasal drug delivery are reviewed. Advances in the LNIT delivery system which have overcome previous limitations demonstrate promising effects.

LNIT presents a judicious alternative for noninjection AIT. The evidences from previous clinical trials and the novel improvement of drug delivery system will lead into the future allergen vaccine production.
Clinical phenotypes of adult atopic dermatitis and related therapies
Authors: Patruno Cataldo , Potestio Luca , Napolitano Maddalena
Published: July 2022

Purpose of review

To report current knowledge on the different clinical phenotypes of adult atopic dermatitis. Possible therapeutic intervention in relation to phenotype is also evaluated.

Recent findings

Atopic dermatitis is a chronic inflammatory disease affecting up to 10% of adults. It can manifest with different clinical phenotypes, causing diagnostic difficulties. Long-term is often required and systemic drugs are needed for moderate-to-severe forms. However, few drugs are registered for atopic dermatitis in many countries. Furthermore, limited data exist regarding the treatment in relation to individual clinical phenotypes.

Currently, the most relevant data are those for cyclosporine, alitretinoin, and dupilumab. Cyclosporine and dupilumab showed to be effective in the treatment of atopic dermatitis, although in trials and real-life experiences the different phenotypes treated are usually not reported. However, cyclosporine appears to be effective in prurigo nodularis. Alitretinoin is reported to be particularly efficacious for atopic dermatitis of the hands, while it is ineffective for other locations of the disease. Dupilumab demonstrated its efficacy in prurigo nodularis and nummular eczema phenotypes of atopic dermatitis; moreover, especially in elderly patients, its effectiveness seems to be faster if the folds of the limbs are involved.
Neurostimulation for dry eye disease
Authors: Erdinest Nir , Pincovich Shirley , London Naomi , Solomon Abraham
Published: July 2022

Purpose of review

To review the neuroanatomy and physiology of the basal and reflex tearing and present the available and developing therapies using the concept of neurostimulation in dry eye disease (DED).

Recent findings

The most prevalent current DED treatments seek to supplement low tear volume and tear components or reduce inflammation. Neurostimulation is a unique approach gaining momentum in recent years, geared toward increasing the production of all basal tear components by stimulating the nerves responsible for producing the various tear components. The neuroanatomy of the lacrimal unit provides several possible access points to stimulate tear production through two arms of the sensory trigeminal nerves. Modes of stimulation include chemical or energy in electrical or magnetic form. Research thus far has shown that neurostimulation can achieve lacrimal, goblet cell, and meibomian gland stimulation. Subjectively it improves symptoms of DED. Clinically, neurostimulation has improved the signs and symptoms of DED by increasing basal tear production and tear volume.

Neurostimulation using electrical, mechanical, or chemical means is a novel concept to increase tear production and was demonstrated to be an effective, safe, and well-tolerated method for managing DED.
Role of therapeutic contact lenses in management of corneal disease
Authors: Wang Yvonne , Jacobs Deborah S.
Published: July 2022

Purpose of review

The current review highlights areas of innovation and research in the use of contact lenses in the treatment of corneal ectasia and ocular surface disease.

Recent findings

A series of academic reports were published by a committee of experts reviewing evidence-based practice patterns of contact lens use. There continues to be active research in the use of contact lenses in the management of keratoconus, including mini-scleral lenses, custom impression-based scleral lenses and wavefront-guided scleral lenses. Recent reports on contact lenses for ocular surface disease were primarily reviews, retrospective case reports or case series, with publications on contact lens use in corneal epithelial defects, graft-vs.-host disease, limbal stem cell deficiency and neurotrophic keratitis. There are recent publications on advances in drug-eluting contact lenses.

Corneal specialists should be aware of current advances in the field of contact lens expanding their use in corneal ectasia and ocular surface disease.
Indications for keratoplasty in management of corneal ectasia
Authors: Choi Jamie H. , Jeng Bennie H.
Published: July 2022

Purpose of review

The current review aims to describe recent advancements in treatment of corneal ectasias and its effect on indications for corneal transplantation.

Recent findings

The majority of patients affected by ectatic corneal disease use contact lenses to correct resulting astigmatism. Patients who are intolerant of contact lenses or cannot achieve acceptable vision through conservative measures could consider keratoplasty. However, continuing advancements in both nonsurgical and surgical treatments are either reducing or delaying the need for keratoplasty in patients affected by ectatic corneal disease.

Corneal transplantation has been the mainstay of treatment for patients with advanced ectatic corneal disease. In the past decade, numerous improvements have been occurred to make contact lenses not only more effective for visual correction, but also more comfortable. Although corneal cross-linking is the only proven treatment known to prevent progression of disease, several other therapies show early potential for those in which cross-linking is contraindicated. Patients now have access to a wider range of therapies before considering keratoplasty.
Pilocarpine 1.25% and the changing landscape of presbyopia treatment
Authors: Meghpara Beeran B. , Lee Jimmy K. , Rapuano Christopher J. , Mian Shahzad I. , Ho Allen C.
Published: July 2022

Purpose of review

Despite affecting approximately 1.8 billion individuals worldwide, until recently, a pharmacologic treatment for presbyopia was not available. This special commentary reviews the treatment of presbyopia with a focus on the recently approved medication Vuity (pilocarpine 1.25%, Allergan, an AbbVie Company).

Recent Findings

Vuity is a re-engineered formulation of pilocarpine 1.25% specifically designed for the treatment of presbyopia. Recently published results from the GEMINI 1 Phase 3 clinical trial reported improvement in distance corrected near vision without significant compromise in distance vision. No unexpected safety findings were reported with mild headache being the most common adverse event. Notably, there were no reported cases of retinal detachment or angle closure during the 30-day phase 3 clinical trials.

Vuity is the first treatment designed and FDA approved to treat the growing presbyopia market. Phase 3 clinical trials demonstrated its ability to improve near vision without significant compromise in distance vision. We recognize this paradigm shift in the treatment of presbyopia and anxiously await additional treatment options for this ubiquitous condition.
Descemet membrane endothelial keratoplasty in complex eyes
Authors: Siddiqui Aazim , Chamberlain Winston D.
Published: July 2022

Purpose of review

To review the current literature on Descemet membrane endothelial keratoplasty (DMEK) in complex eyes.

Recent findings

DMEK surgery has become a standardized procedure in Fuchs endothelial dystrophy and simple bullous keratopathy. But eyes with more complex disease present unique intraoperative and postoperative challenges to the DMEK surgeon. Poor visualization during surgery, complex anterior segment anatomy, altered anterior chamber dynamics, glaucoma shunts, and congenital or iatrogenic missing or altered iris and lens make DMEK surgery extremely difficult to accomplish.

DMEK is feasible in complex eyes, including advanced bullous keratopathy, eyes with history of glaucoma or vitreoretinal surgery, previous penetrating keratoplasty, uveitis, pediatric, and congenital anterior segment disorders. The tools and methods reported in the literature to accomplish DMEK in complex eyes vary widely with no particular consensus or standardization of techniques. The outcomes noted for some of these conditions demonstrate the difficulty of the surgery and the uncertainty of long-term graft survival in complex eyes. Both surgical standardization and randomized prospective data will better help elucidate DMEK's role in the corneal rehabilitation of complex eyes.
The preoperative management of meibomian gland dysfunction prior to corneal refractive surgery
Authors: Tauber Jenna , Kennedy Thomas , Juthani Viral
Published: July 2022

Purpose of review

To describe the significance of meibomian gland dysfunction (MGD) in corneal refractive surgery and to describe available approaches to preoperative evaluation and treatment based on current research.

Recent findings

There are several methods available for the evaluation and treatment of MGD. These are relevant for refractive surgeons to understand, as the presence of MGD preoperatively plays a role in the severity of MGD after corneal refractive surgery. Refractive surgery itself can exacerbate MGD. Treatment of MGD prior to surgery may have a meaningful impact on postoperative MGD.

Surgeons should include meibomian gland assessment in the preoperative refractive evaluation and should treat MGD proactively prior to performing refractive surgery. Relevant information in this field is growing; additional prospectively designed studies are needed to further enhance our understanding.
Epithelial thickness mapping for corneal refractive surgery
Authors: Reinstein Dan Z. , Archer Timothy J. , Vida Ryan S.
Published: July 2022

Purpose of review

As more devices become available that offer corneal epithelial thickness mapping, this is becoming more widely used for numerous applications in corneal refractive surgery.

Recent findings

The epithelial thickness profile is nonuniform in the normal eye, being thinner superiorly than inferiorly and thinner temporally than nasally. Changes in the epithelial thickness profile are highly predictable, responding to compensate for changes in the stromal curvature gradient, using the eyelid as an outer template. This leads to characteristic changes that can be used for early screening in keratoconus, postoperative monitoring for early signs of corneal ectasia, and for determining whether further steepening can be performed without the risk of apical syndrome following primary hyperopic treatment. Compensatory epithelial thickness changes are also a critical part of diagnosis in irregular astigmatism as these partially mask the stromal surface irregularities. The epithelial thickness map can then be used to plan a trans-epithelial PRK treatment for cases of irregularly irregular astigmatism. Other factors can also affect the epithelial thickness profile, including dry eye, anterior basement membrane dystrophy and eyelid ptosis.

Epithelial thickness mapping is becoming a crucial tool for refractive surgery, in particular for keratoconus screening, ectasia monitoring, hyperopic treatment planning, and therapeutic diagnosis and treatment.
Local axonal translation sustains synapse-type-specific neurotransmission
Authors: Wong Hovy Ho-Wai , Watt Alanna J. , Sjöström P. Jesper
Published: July 2022

Dendritic protein synthesis is a well-known regulator of neurotransmission in the central nervous system. For example, local on-demand protein synthesis in dendrites is required for hippocampal long-term1,2 and homeostatic plasticity3. Although axonal protein synthesis is a key regulator in neural circuit assembly during early development4–6, it is unclear if local translation in mature axons plays a functional role in neurotransmission of the mammalian central nervous system. Here we show that local translation in axons regulates pyramidal cell neurotransmission in primary visual cortex microcircuits in a synapse-type-specific manner7,8. Using paired recordings to manipulate pre- and postsynaptic neurons independently, we found that presynaptic translation sustains neurotransmission and regulates short-term plasticity. This was mediated via mTOR and cap-dependent translation, with presynaptic NMDA receptors acting as an up-stream trigger. By isolating the axon from the soma with laser microsurgery, we unveiled that axonal translation was required to sustain neurotransmission. With live endogenous RNA imaging, we found that RNA granules stably docked in individual presynaptic compartments, suggesting bouton-specific regulation. In agreement, presynaptic translation influenced pyramidal cell synapses to neighbouring pyramidal cells, but not to inhibitory Martinotti cells. Our study establishes local protein synthesis in mature axons as a fundamental regulatory principle that governs information transfer at central synapses.
The Unmet Needs of People with Parkinson’s Disease and How They Relate to Current Late-Stage Clinical Trials
Authors: Moon Jasmine , Javidnia Monica
Published: July 2022

Objective

To identify the symptoms and unmet needs of people with Parkinson’s Disease and characterize Phase 2-3 and Phase 3 clinical trials.

Methods

We surveyed people with Parkinson’s Disease to determine their symptoms, pharmacological and non-pharmacological treatments, side effects, and insufficiently managed or unmanaged symptoms, and wishes for Parkinson’s Disease research. We identified clinical trials through clinicaltrials.gov.

Results

Twenty-eight people with Parkinson’s Disease completed the study (22 survey, six interview), and 38 clinical trials were characterized. The majority of participants’ desires for clinical development and outcomes of clinical trials characterized targeted motor symptoms.

Conclusions

Despite numerous therapeutics available, motor symptoms continue to be a top priority for people with Parkinson’s Disease and focus for drug development.

All relevant ethical guidelines have been followed, all necessary IRB and/or ethics committee approvals have been obtained, all necessary patient/participant consent has been obtained and the appropriate institutional forms archived.
Early seral vegetation communities increase insect abundance and diversity in a semiarid natural gas field during early and late growing season
Authors: Curran Michael F. , Sorenson Joshua R. , Craft Zoe A. , Crow Taylor M. , Robinson Timothy J. , Stahl Peter D.
Published: July 2022

Insects are critical components of terrestrial ecosystems and are often considered ecosystem engineers. Due to the vast amount of ecosystem services they provide, because statistically valid samples can be captured in short durations, and because they respond rapidly to environmental change, insects have been used as indicators of restoration success and ecosystem functionality. In Wyoming (USA), thousands of acres of land surface has been disturbed to extract natural resources. While traditional reclamation practices of these lands focused on site stabilization and weed control, more recent efforts have been made to restore ecosystem services. It has been suggested that a spatial and temporal mosaic of flowering species will benefit insect populations. In this study, we compared early seral reclamation sites (i.e., well pads undergoing interim reclamation) to reference areas at two points within a growing season. We found reference ecosystems were devoid of forb species, while one year old reclaimed sites contained late-season blooming Rocky Mountain beeplant (Cleome serrulata) and three-four year old well pads contained early-season blooming perennial forb species, mainly western yarrow (Achillea millefolium). We compared insect abundance and family richness on 6 well pads with early season perennial forbs and 6 well pads with the late season annual forb, Rocky Mountain beeplant to insect communities on adjacent reference areas. A total of 237 insects were found on early season reclaimed sites compared to 84 on reference sites, while 858 insects were found on late season reclaimed sites compared to 40 on reference sites. Insect abundance and family richness was significantly higher on reclaimed well pads compared to reference areas at both points in the growing season. We also found interesting differences in abundance at family levels.
netANOVA: novel graph clustering technique with significance assessment via hierarchical ANOVA
Authors: Duroux Diane , Van Steen Kristel
Published: July 2022

Many problems in life sciences can be brought back to a comparison of graphs. Even though a multitude of such techniques exist, often, these assume prior knowledge about the partitioning or the number of clusters and fail to provide statistical significance of observed between-network heterogeneity. Addressing these issues, we developed an unsupervised workflow to identify groups of graphs from reliable network-based statistics. In particular, we first compute the similarity between networks via appropriate distance measures between graphs and use them in an unsupervised hierarchical algorithm to identify classes of similar networks. Then, to determine the optimal number of clusters, we recursively test for distances between two groups of networks. The test itself finds its inspiration in distance-wise ANOVA algorithms. Finally, we assess significance via the permutation of between-object distance matrices. Notably, the approach, which we will call netANOVA, is flexible since users can choose multiple options to adapt to specific contexts and network types. We demonstrate the benefits and pitfalls of our approach via extensive simulations and an application to two real-life datasets. NetANOVA achieved high performance in many simulation scenarios while controlling type I error. On non-synthetic data, comparison against state-of-the-art methods showed that netANOVA is often among the top performers. There are many application fields, including precision medicine, for which identifying disease subtypes via individual-level biological networks improves prevention programs, diagnosis, and disease monitoring.
Modelling Instantaneous Firing Rate of DBS Target Neuronal Ensembles in Basal Ganglia and Thalamus
Authors: Tian Yupeng , Murphy Matthew J. H. , Steiner Leon A , Kalia Suneil K , Hodaie Mojgan , Lozano Andres M , Hutchison William D , Milos R. Popovic , Luka Milosevic , Milad Lankarany
Published: July 2022

Objective

Deep Brain Stimulation (DBS) is an effective treatment for movement disorders, including Parkinson’s disease and essential tremor. However, the underlying mechanisms of DBS remain elusive. Despite the capability of existing models in interpreting experimental data qualitatively, there are very few unified computational models that quantitatively capture the dynamics of the neuronal activity of varying stimulated nuclei—including subthalamic nucleus (STN), substantia nigra pars reticulata (SNr) and ventral intermediate nucleus (Vim)—across different DBS frequencies.

Materials and Methods

Both synthetic and experimental data were utilized in the model fitting; the synthetic data were generated by an established spiking neuron model that was reported in our previous work1, and the experimental data were provided using single-unit microelectrode recordings (MER) during DBS (microelectrode stimulation). Based on these data, we developed a novel mathematical model to represent the firing rate of neurons receiving DBS, including neurons in STN, SNr and Vim—across different DBS frequencies. In our model, the DBS pulses were filtered through a synapse model and a nonlinear transfer function to formulate the firing rate variability. For each DBS-targeted nucleus, we fitted a single set of optimal model parameters consistent across varying DBS frequencies.

Results

Our model accurately reproduced the firing rates observed and calculated from both synthetic and experimental data. The optimal model parameters were consistent across different DBS frequencies.

Conclusion

The result of our model fitting were in agreement with experimental single-unit microelectrode recording data during DBS. Reproducing neuronal firing rates of different nuclei of the basal ganglia and thalamus during DBS can be helpful to further understand the mechanisms of DBS, and to potentially optimize stimulation parameters based on their actual effects on neuronal activity.
A pals-25 gain-of-function allele triggers systemic resistance against natural pathogens of C. elegans
Authors: Gang Spencer S. , Grover Manish , Reddy Kirthi C. , Raman Deevya , Chang Ya-Ting , Ekiert Damian C. , Barkoulas Michalis , Troemel Emily R.
Published: July 2022

Regulation of immunity throughout an organism is critical for host defense. Previous studies in the nematode Caenorhabditis elegans have described an “ON/OFF” immune switch comprised of the antagonistic paralogs PALS-25 and PALS-22, which regulate resistance against intestinal and epidermal pathogens. Here, we identify and characterize a PALS-25 gain-of-function mutant protein with a premature stop (Q293*), which we find is freed from physical repression by its negative regulator, the PALS-22 protein. PALS-25(Q293*) activates two related gene expression programs, the Oomycete Recognition Response (ORR) against natural pathogens of the epidermis, and the Intracellular Pathogen Response (IPR) against natural intracellular pathogens of the intestine. A subset of ORR/IPR genes is upregulated in pals-25(Q293*) mutants, and they are resistant to oomycete infection in the epidermis, and microsporidia and virus infection in the intestine, but without compromising growth. Surprisingly, we find that activation of PALS-25 seems to primarily stimulate the downstream bZIP transcription factor ZIP-1 in the epidermis, which leads to upregulation of gene expression in both the epidermis and in the intestine. Interestingly, we find that this epidermal-to-intestinal signaling promotes resistance to the N. parisii intestinal pathogen, demonstrating cross-tissue protective immune induction from one epithelial tissue to another in C. elegans.

Author summary

Multicellular organisms need to monitor the health and function of multiple tissues simultaneously to respond appropriately to pathogen infection. Here, we study an ON/OFF switch in the roundworm C. elegans that controls immune responses to diverse natural pathogens of the skin and gut. We show a physical association between the ‘ON switch’ protein PALS-25 and the ‘OFF switch’ protein PALS-22, and that this association is disrupted in a mutant, activated form of PALS-25. When either PALS-22 is lost, or PALS-25 is activated, a downstream immune regulator ZIP-1 is activated specifically in the skin but not the gut. Excitingly, our findings show that skin-specific loss of PALS-22 or skin-specific activation of PALS-25 can induce immune responses in the worm gut. These findings highlight the coordination of immune responses across different tissues that are commonly infected by microbial pathogens.
Recognition of non-self is necessary to activate Drosophila’s immune response against an insect parasite
Authors: Leitão Alexandre B. , Arunkumar Ramesh , Day Jonathan P. , Hanna Nancy , Devi Aarathi , Hayes Matthew P. , Jiggins Francis
Published: July 2022

Innate immune responses can be activated by pathogen-associated molecular patterns (PAMPs) or danger signals released by damaged tissues. As PAMPs are typically conserved across broad groups of pathogens but absent from the host, it is unclear whether they allow hosts to recognize parasites that are phylogenetically related to themselves, such as parasitoid wasps infecting insects. Parasitoids must penetrate the cuticle of Drosophila larvae to inject their eggs. In line with previous results, we find that the danger signal of wounding triggers the differentiation of specialized immune cells called lamellocytes. However, using oil droplets to mimic infection by a parasitoid wasp egg, we find that the activation of melanization response that kills parasitoids also requires exposure to a parasitoid wasp molecule that acts as a PAMP. The unidentified factor enhances the transcriptional response in hemocytes and induces a specific response in the fat body that includes Tep1, which is essential for efficient melanization. We conclude that a combination of danger signals and PAMPs are required activate Drosophila’s immune response against parasitic insects.