bluuebunny/crossref_metadata_2025 huggingface dataset:
General Anesthesia versus Sedation, Both with Hemodynamic Control, during Intraarterial Treatment for Stroke: The GASS Randomized Trial
Authors: Maurice Axelle , Eugène François , Ronzière Thomas , Devys Jean-Michel , Taylor Guillaume , Subileau Aurélie , Huet Olivier , Gherbi Hakim , Laffon Marc , Esvan Maxime , Laviolle Bruno , Beloeil Helene ,   for the GASS (General Anesthesia versus Sedation for Acute Stroke Treatment) Study Group and the French Society of Anesthesiologists (SFAR) Research Network
Published: February 2022

Background

It is speculated that the anesthetic strategy during endovascular therapy for stroke may have an impact on the outcome of the patients. The authors hypothesized that conscious sedation is associated with a better functional outcome 3 months after endovascular therapy for the treatment of stroke compared with general anesthesia.

Methods

In this single-blind, randomized trial, patients received either a standardized general anesthesia or a standardized conscious sedation. Blood pressure control was also standardized in both groups. The primary outcome measure was a modified Rankin score less than or equal to 2 (0 = no symptoms; 5 = severe disability) assessed 3 months after treatment. The main secondary outcomes were complications, mortality, reperfusion results, and National Institutes of Health Stroke Scores at days 1 and 7.

Results

Of 351 randomized patients, 345 were included in the analysis. The primary outcome occurred in 129 of 341 (38%) of the patients: 63 (36%) in the conscious sedation group and 66 (40%) in the general anesthesia group (relative risk, 0.91 [95% CI, 0.69 to 1.19]; P = 0.474). Patients in the general anesthesia group experienced more intraoperative hypo- or hypertensive episodes, while the cumulative duration was not different (mean ± SD, 36 ± 31 vs. 39 ± 25 min; P = 0.079). The time from onset and from arrival to puncture were longer in the general anesthesia group (mean difference, 19 min [i.e., −00:19] [95% CI, −0:38 to 0] and mean difference, 9 min [95% CI, −0:18 to −0:01], respectively), while the time from onset to recanalization was similar in both groups. Recanalization was more often successful in the general anesthesia group (144 of 169 [85%] vs. 131 of 174 [75%]; P = 0.021). The incidence of symptomatic intracranial hemorrhage was similar in both groups.

Conclusions

The functional outcomes 3 months after endovascular treatment for stroke were similar with general anesthesia and sedation. Our results, therefore, suggest that clinicians can use either approach.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Basal Infusion versus Automated Boluses and a Delayed Start Timer for “Continuous” Sciatic Nerve Blocks after Ambulatory Foot and Ankle Surgery: A Randomized Clinical Trial
Authors: Finneran John J. , Said Engy T. , Curran Brian P. , Swisher Matthew W. , Black Jessica R. , Gabriel Rodney A. , Sztain Jacklynn F. , Abramson Wendy B. , Alexander Brenton , Donohue Michael C. , Schaar Adam , Ilfeld Brian M.
Published: February 2022

Background

The common technique using a basal infusion for an ambulatory continuous peripheral nerve blocks frequently results in exhaustion of the local anesthetic reservoir before resolution of surgical pain. This study was designed to improve and prolong analgesia by delaying initiation using an integrated timer and delivering a lower hourly volume of local anesthetic as automated boluses. The hypothesis was that compared with a traditional continuous infusion, ropivacaine administered with automated boluses at a lower dose and 5-h delay would (1) provide at least noninferior analgesia (difference in average pain no greater than 1.7 points) while both techniques were functioning (average pain score day after surgery) and (2) result in a longer duration (dual primary outcomes).

Methods

Participants (n = 70) undergoing foot or ankle surgery with a popliteal–sciatic catheter received an injection of ropivacaine 0.5% with epinephrine (20 ml) and then were randomized to receive ropivacaine (0.2%) either as continuous infusion (6 ml/h) initiated before discharge or as automated boluses (8 ml every 2 h) initiated 5 h after discharge using a timer. Both groups could self-deliver supplemental boluses (4 ml, lockout 30 min); participants and outcome assessors were blinded to randomization. All randomized participants were included in the data analysis.

Results

The day after surgery, participants with automated boluses had a median [interquartile range] pain score of 0.0 [0.0 to 3.0] versus 3.0 [1.8 to 4.8] for the continuous infusion group, with an odds ratio of 3.1 (95% CI, 1.23 to 7.84; P = 0.033) adjusting for body mass index. Reservoir exhaustion in the automated boluses group occurred after a median [interquartile range] of 119 h [109 to 125] versus 74 h [57 to 80] for the continuous infusion group (difference of 47 h; 95% CI, 38 to 55; P < 0.001 adjusting for body mass index).

Conclusions

For popliteal–sciatic catheters, replacing a continuous infusion initiated before discharge with automated boluses and a start-delay timer resulted in better analgesia and longer infusion duration.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Telehealth Utilization and Follow-Up Visits in Developmental-Behavioral Pediatrics During the COVID-19 Pandemic in 2020
Authors: Ripp Asher , Steinway Caren , Katzow Michelle Weiss , Jan Sophia , Chen Jack , Chen Victoria
Published: February 2022

Objective:

The goal of this study was to understand the effect of transition to telehealth care on follow-up visit attendance in a developmental-behavioral pediatric (DBP) practice in 2020 versus in-person care in 2019.

Methods:

This was a retrospective observational cohort study of follow-up visits occurring in a large DBP practice during a 6-week period in March/April of 2019 and 2020. The primary outcome was follow-up visit adherence, defined as completion of scheduled follow-up visit. The primary exposure was telehealth visit in 2020 versus in-person visit in 2019. Covariates included patient demographics and clinical characteristics. Data were analyzed using descriptive statistics and logistic regression.

Results:

The cohort included 2142 visits for 1868 unique patients. The patient mean age was 9.2 ± 4.8 years, with 73.4% male, 56.5% non-Hispanic, 51.4% White, and 68.3% commercial insurance. There were 470 telehealth visits from March to April 2020 and 1672 in-person visits from March to April 2019. Compared with in-person visits, telehealth visits were more likely to be completed (75.3% vs 64.4%, p < 0.001). After adjusting for age, sex, race, ethnicity, insurance, and week of visit (weeks 1–3 vs 4–6), odds of having a complete follow-up visit were higher for telehealth visits than for in-person visits (odds ratio = 1.57; 95% confidence interval [1.23–2.00], p < 0.001).

Conclusion:

Follow-up visit attendance was higher for telehealth care in 2020 than in-person care in 2019. This association persisted after adjusting for insurance, age, race, and ethnicity, suggesting that telehealth is associated with increased follow-up visit attendance in DBP care. Further studies are needed to understand the impact of telehealth on DBP clinical outcomes in chronic disease management.
Prevention of multiple pregnancies in gonadotropin-insemination cycles
Authors: Dahdouh Elias M. , Zreik Tony G. , Ghaname Wadih , Garcia-Velasco Juan A. , Balayla Jacques
Published: February 2022

Purpose of review

Although elective single embryo transfer has significantly reduced, the rate of multiple pregnancy in IVF cycles, this rate is still relatively high in gonadotropin-insemination cycles. Patients who fail to ovulate or to conceive with oral agents and have constraints for IVF are usually candidates for gonadotropin injections. The current review article provides an up-to-date summation of the different strategies that can be adopted to reduce the risk of multiple pregnancies in gonadotropin-stimulated intrauterine insemination cycles.

Recent findings

Gonadotropin-insemination treatments should be used judiciously by experienced providers. One should always start with the lowest effective gonadotropin dose (∼37.5 IU), monitor closely the ovarian response, and consider cycle cancellation or conversion to IVF whenever a high response is encountered. Therefore, every infertility practice should define its own cancellation and ‘rescue IVF’ criteria depending on the number of mature ovarian follicles and the age of the female partner.

These preventive measures amongst others should mitigate the risk of multiple pregnancies that can arise from gonadotropin-insemination cycles.
Partial Second Toe Pulp Flap Transfer for the Coverage of Great Toe Hemipulp Flap Donor Site
Authors: Hattori Yoshitsugu , Tamemoto Tomoyuki , Niu Atsushi
Published: February 2022

The great toe hemipulp flap transfer is a viable reconstructive method for finger pulp defect. However, early functional recovery of the donor foot is essential for returning to daily life activities, and functional and aesthetic restoration of the donor site remains challenging. We present a case in which the great toe hemipulp flap donor site was reconstructed with pedicled partial second toe pulp flap transfer, aiming for early recovery of the donor foot and aesthetically and functionally satisfactory donor-site reconstruction. A 62-year-old man underwent left little finger-pulp crush amputation in Tamai zone 2 and received free great toe hemipulp flap transfer. For the defect following flap harvest, the partial second toe pulp flap was elevated and transferred. The donor site of the partial second toe pulp flap was primarily closed. The postoperative course was uneventful, and the patient started walking on postoperative day 2. Postoperatively, the sensory recovery of the transferred flap was excellent, and the reconstructed great toe was functionally and aesthetically satisfactory. The pedicled partial second toe pulp flap transfer may be a viable alternative for the coverage of great toe hemipulp flap donor site.
Risk Reduction Strategies for Adolescent Cannabis Use Considering COVID-19 Stressors
Authors: Mayfield Brenda L. , Fogger Susanne Astrab
Published: February 2022

The past 2 years has been a challenge as society made huge adaptations to keep people safe from COVID-19 and struggled to continue life on a day-to-day basis. Working with families, young adults, and adolescents, nurses are often faced with caring for individuals who recreationally use cannabis and believe use is harmless. Adolescents as a group tend to appraise information from a different lens than adults. In an evolving world, where cannabis is legalized for medicinal and recreational use, it is important to shift the paradigm of how we approach cannabis use in adolescents. This article will focus on COVID-19's impact on cannabis use in adolescents and apply the transtheoretical model of change to promote safer choices while supporting adolescent autonomy. In addition, we will incorporate behavioral health strategies to reduce risks of cannabis use by equipping adolescents with guidelines, boundaries, and tools.
Overcoming Barriers to Human Papillomavirus Vaccination
Authors: Domurat Paige A. , Nickasch Bonnie L.
Published: February 2022

Introduction

Despite the human papillomavirus (HPV) vaccine's ability to help prevent certain types of cancer, rates of vaccination against HPV remain low, and choosing to have a child receive the HPV vaccine has become a controversial topic. The primary objective of this quality improvement project was to increase HPV vaccination rates through creating and distributing an all-in-one education and reminder system to pediatric clinic patients and their families once patients are eligible to receive the HPV vaccination.

Methods

Three barriers to increasing rates of HPV vaccination were identified: cost, lack of knowledge, and lack of provider recommendation. A flyer system was implemented that addressed these barriers. This flyer was given to all patients ages 11–18 years, with a strong verbal provider recommendation.

Results

One-sample proportion tests were run to determine significance in the differing series completion rates in 2018, 2019, and 2020. The pediatric clinic's HPV vaccination series completion rates increased significantly from 2018 to 2019. During the implementation of this flyer system, which occurred during the COVID-19 pandemic, the vaccination series completion rates decreased, but this decrease was not statistically significant.

Discussion

As control is gained over the pandemic, it is anticipated that regular provider visits will increase back to normal and therefore vaccination rates will recover as well. The findings from this study can be used to create or modify current practices in clinics anywhere that the HPV vaccination is administered. Future studies and trials should be implemented for a longer period, and not during a pandemic, ideally to yield more statistically significant results.
Contemporary risk prediction models in chronic kidney disease: when less is more
Authors: Canney Mark , Sood Manish M. , Hundemer Gregory L.
Published: February 2022

Purpose of review

Clinicians have an ever-increasing number of prediction tools at their disposal for estimating the risk of kidney failure in their patients. This review aims to summarize contemporary evidence for chronic kidney disease (CKD) risk prediction models across the spectrum of kidney function, and explore nuances in the interpretation of risk estimates.

Recent findings

A European study using predominantly laboratory data has extended kidney failure prediction to patients with more preserved estimated glomerular filtration rate. For older patients with advanced CKD, prediction tools that censor for death (such as the Kidney Failure Risk Equation) overestimate the risk of kidney failure, especially over time horizons longer than 2 years. This problem can be addressed by accounting for the competing risk of death, as shown in well designed validation studies. The clinical utility of kidney failure risk prediction tools is being increasingly tested at a population level to inform policy and referral guidelines.

There is welcome trend to validate existing prediction tools in diverse clinical settings and identify their role in clinical practice. Clinicians should be cognizant of overestimating kidney failure risk in older patients with advanced CKD due to the competing risk of death. For moderate CKD and for short-term predictions, the Kidney Failure Risk Equation remains the most widely validated prediction tool.
Update on preclinical and clinical efforts on ex-vivo expansion of hematopoietic stem and progenitor cells
Authors: Huang Xinxin , Guo Bin
Published: February 2022

Purpose of review

Ex-vivo expansion of hematopoietic stem cells (HSCs) is one potential approach to enhance the clinical efficacy of hematopoietic cell transplantation-based therapy for malignant and nonmalignant blood diseases. Here, we discuss the major progress of preclinical and clinical studies on the ex-vivo expansion of human HSCs and progenitor cells (HPCs).

Recent findings

Single-cell RNA sequencing identified ADGRG1 as a reliable marker of functional HSCs upon ex-vivo expansion-induced mitochondrial oxidative stress. Both SR1 and UM171 significantly promote ex-vivo expansion of human cord blood HSCs and HPCs, as determined in preclinical animal models. Encouraged by these findings from the bench, multiple phase I/II and phase II clinical trials have been conducted to evaluate the safety, feasibility and efficacy of SR1-expanded and UM171-expanded cord blood units in patients with hematological malignancy.

Preliminary data from multiple phase I/II clinical trials regarding transplants of ex-vivo-expanded HSCs and HPCs have demonstrated that ex-vivo expansion may be used to overcome the limitation of the rarity of HSCs without compromising stemness.
Randomized, Double‐Blind, Placebo‐Controlled Study to Assess the Effect of Two Probiotics on the Preterms’ Gut Microbiota
Authors: Moreno‐Sanz Bárbara , Montes María Teresa , Manzano Susana , Espinosa‐Martos Irene , Cárdenas Nivia , Esteban Sergio , Cruz Marta , Jiménez Esther , de Pipaón Miguel Sáenz
Published: February 2022

Objective:

To evaluate the effect of a new probiotic strain combination, Ligilactobacillus salivarius subsp infantis PS11603 and Bifidobacterium longum PS10402, on gut bacterial colonization of preterm infants.

Methods:

A randomized, double‐blind, placebo‐controlled study was conducted in preterm infants from 28 weeks + 0days to 30 weeks + 6days of gestation. Thirty preterm infants were randomly selected after birth to receive either probiotics or placebo. Stool samples were collected before product intake and then sequentially during the first weeks of their admission. Classical microbiological, metagenomics and multiplex immunological analyses were performed to assess the bacterial and immune profile of the samples.

Results:

Twenty‐seven infants completed the study (14 vs 13, probiotic and placebo groups). A higher number of participants were colonized by Lactobacilli in the probiotic group than in the placebo group (93% vs 46%; P = 0.013). Similar results were obtained when analysing bifidobacterial colonization (100% vs 69%; P = 0.041). Earlier colonization was observed in the probiotics group versus the placebo group, specifically 5 weeks for Lactobacillus and 1 week for Bifidobacterium. Although no effect was observed in the faecal immunological profile, a decreasing trend could be observed in Th17 response during the first week of probiotic treatment. None of the adverse events (AEs) registered were related to product intake.

Conclusion:

Probiotic supplementation with L salivarius PS11603 and B longum subsp. infantis PS10402 enhanced an earlier colonization of Lactobacillus and Bifidobacterium in preterm infants’ guts in 5 and 1 week, respectively. A higher number of infants were colonized by Lactobacilli with the probiotics’ intake at the end of the study.
Magnetic Resonance Elastography in Intracranial Neoplasms: A Scoping Review
Authors: Aunan-Diop Jan Saip , Halle Bo , Pedersen Christian Bonde , Jensen Ulla , Munthe Sune , Harbo Frederik , Andersen Mikkel Schou , Poulsen Frantz Rom
Published: February 2022

Background:

Magnetic resonance elastography (MRE) allows noninvasive assessment of intracranial tumor mechanics and may thus be predictive of intraoperative conditions. Variations in the use of technical terms complicate reading of current literature, and there is need of a review using consolidated nomenclature.

Objectives:

We present an overview of current literature on MRE relating to human intracranial neoplasms using standardized nomenclature suggested by the MRE guidelines committee. We then discuss the implications of the findings, and suggest approaches for future research.

Method:

We performed a systematic literature search in PubMed, Embase, and Web of Science; the articles were screened for relevance and then subjected to full text review. Technical terms were consolidated.

Results:

We identified 12 studies on MRE in patients with intracranial tumors, including meningiomas, glial tumors including glioblastomas, vestibular schwannomas, hemangiopericytoma, central nervous system lymphoma, pituitary macroadenomas, and brain metastases. The studies had varying objectives that included prediction of intraoperative consistency, histological separation, prediction of adhesiveness, and exploration of the mechanobiology of tumor invasiveness and malignancy. The technical terms were translated using standardized nomenclature. The literature was highly heterogeneous in terms of image acquisition techniques, post-processing, and study design and was generally limited by small and variable cohorts.

Conclusions:

MRE shows potential in predicting tumor consistency, adhesion, and mechanical homogeneity. Furthermore, MRE provides insight into malignant tumor behavior and its relation to tissue mechanics. MRE is still at a preclinical stage, but technical advances, improved understanding of soft tissue rheological impact, and larger samples are likely to enable future clinical introduction.
Is 3-Dimensional Scanning Really Helpful in Implant-Based Breast Reconstruction?
Authors: Huang Dun-Wei , Chou Yu-Yu , Liu Hung-Hui , Dai Niann-Tzyy , Tzeng Yuan-Sheng , Chen Shyi-Gen
Published: February 2022

Background

Breast reconstruction is an integral part of breast cancer treatment, and implant-based breast reconstruction is the most commonly used method worldwide. However, there is still no technique that allows surgeons to predict the volume of the required implant. Although computed tomography and magnetic resonance imaging provide adequate representations of the breast, these procedures are time-consuming, expensive, and expose patients to radiation. Therefore, there is a need for safer, noninvasive alternatives for preoperative breast volume measurements.

Patients and Methods

This study is a prospective review of 12 patients with early-stage breast cancer who underwent nipple-sparing mastectomy and immediate breast reconstruction with implants. Preoperatively, the Artec Eva 3D scanner was used to acquire volumetric measurements of the breasts. Intraoperatively, the volume of the mastectomy specimen was measured using the water displacement method. Correlations among the preoperative breast, mastectomy specimen, and estimated and final implant volumes were analyzed through Pearson correlation coefficient. A correction prediction factor of 85% was applied where necessary. Patient and physician satisfaction were evaluated 3 months postoperatively.

Results

Our study found a statistically significant correlation between the preoperative breast volumes measured by the Artec Eva 3D scanner and intraoperative mastectomy specimen volumes (r = 0.6578). There was no correlation between the preoperative breast volumes and final implant volumes, mastectomy specimen volumes and final implant volumes, and estimated implant volumes and final implant volumes.

Conclusions

Although the Artec Eva 3D scanner can offer relatively accurate measurement of breast volumes, multiple studies still need to be done to determine how these data can be applied to the mastectomy procedure and breast implant selection. It may be more applicable for preoperative planning in breast augmentation surgery. Future surgeons should also take into account that variabilities in natural breast size, tumor size, cancer stage, and in patient and physician preferences all influence the outcome of breast reconstruction surgery.
Transitioning to a high renewable net-zero power generation system in Malaysia
Authors: Chan Hoy-Yen , Sopian Kamaruzzaman
Published: February 2022

Malaysia is a net importer of coal, petroleum products and piped natural gas. Moreover, its primary energy supply is dominated by fossil fuels, at about 93% in total, with coal and natural gas constituting the highest shares in electricity generation. Thus, there is need for Malaysia to take swift action in transitioning to a high renewable energy system for long-term sustainability and meeting its climate action commitment under the Paris Agreement. A net-zero emissions vision guided by a roadmap may effectively motivate and catalyse carbon-free energy deployments. In this paper, we revisit the carbon-free energy roadmap that was developed in 2015 and compare it with the current generation development plan to identify the gaps between them. We argue that the roadmap is still relevant to the net-zero emissions vision; however, we have also identified gaps that merit further research and improvement. The identified gaps mainly relate to more recent data, along with technology and policy developments. Accordingly, we put forward potential research suggestions to bridge these gaps for future development of a roadmap that would assist Malaysia in shaping a long-term plan towards realizing a high renewable net-zero power generation system.

This article is part of the theme issue ‘Developing resilient energy systems’.
An assessment of the impact of 1.5 versus 2 and 2.5°C global temperature increase on flooding in Jamaica: a case study from the Hope watershed
Authors: Mandal Arpita , Stephenson Tannecia , Campbell Jayaka , Taylor Michael , Watson Shavel , Clarke Leonardo , Smith David , Darsan Junior , Wilson Matthew
Published: February 2022

Climate change models project that, within the Caribbean basin, rainfall intensity is likely to increase toward the end of this century, although the region is projected to be drier overall. This may affect the frequency and severity of floods in Jamaica and the Caribbean Small Island Developing States. We investigate how flood hazards may be affected by increases in global mean surface temperature of 1.5, 2.0 and 2.5°C above pre-industrial levels using a case study of a Jamaican watershed. Rainfall projections from the PRECIS regional climate model for the Caribbean are analysed. Six members from the Quantifying Uncertainty in Model Predictions (AENWH, AEXSA, AEXSC, AEXSK, AEXSL and AEXSM) were used to create 100-year flood inundation maps for the Hope river for different global warming levels using hydrological and hydraulic models. Model runs projected peak discharges at 2.0, 2.5 and 1.5°C warming that were higher than discharges in the historical record of events that damaged sections of the watershed. Projections from the hydraulic model show increased flow area, depth and extent for 1.5 followed by 2.0 and 2.5°C rises in temperature. These results imply continued flood risk for the vulnerable areas of the watershed.

This article is part of the theme issue 'Developing resilient energy systems'.
Sea-level rise, coastal salinity and vegetation changes in Sri Lanka
Authors: Mathiventhan Thavanayagam , Gorman Daniel , Jayasingam Thangamuthu
Published: February 2022

Sea-level rise is a key component of many climate change scenarios. Such increases are expected to cause greater coastal inundation by seawater, reduce the depth of the freshwater-saline water lens and have a range of consequences for coastal ecosystems. Soil salinity determines the distribution patterns of coastal vegetation across a sea-to-land gradient, and sea-level rise would be expected to alter these distributions. Our study done along the east coast of Sri Lanka shows that soil salinity decreases predictably from sea to land, varying between 21‰ and 30‰ over a distance of 50 m from the mean high water springs level. Soil salinity also showed declines with increasing soil depth (0, 10, 50 cm) although this was marginally non-significant. The emergence of terrestrial vegetation coincided with a cross-shore ecotone where the soil salinity approached 0‰. Our predictions suggest that if the mean sea-level were to increase by 1 m in the Batticaloa region (Sri Lanka), this would cause landward communities to be inundated with brackish water at various depths. The present permanent coastal vegetation front would likely shift landward by 30–45 m under scenarios involving a 1 m increase in sea level. Sea-level rise and its consequences could result in a variety of changes to coastal vegetation such as altered physiognomy and diversity, colonization of new territory, expansion of salt-tolerant species such as mangroves and saltmarsh and will therefore greatly influence adaptive management and future planning.

This article is part of the theme issue ‘Developing resilient energy systems’.
Low-cost and open-source super-resolution fluorescence microscope with autofocus for teaching and research
Authors: Hanselman Justin D. , Kopek Benjamin G.
Published: February 2022

Super-resolution fluorescence microscopy revolutionized optical microscopy by breaking the theoretical resolution limit and thus providing an unprecedented view of biological structure in exquisite detail. Additionally, the relative ease of use and implementation for some super-resolution microscopes provided hope that this technology would be widely available and accessible. Despite initial excitement, super-resolution microscopy is still largely limited to facilities that can afford expensive commercial instruments or with personnel experienced in optical engineering that can construct an instrument. Recently, the open scientific hardware movement has attempted to make scientific instrumentation more widely available and accessible in a similar way to the open software movement. The widespread availability and affordability of prototyping devices, such as three-dimensional printers and interfaces (e.g., Arduino) have all contributed to unlocking the potential of the open hardware movement, turning expensive “black box” hardware into open-source, affordable, and robust instrumentation. Many others have recognized the potential of describing low-cost implementations of super-resolution microscope designs. However, we have found these microscope designs lacking in the documentation and details required to meet the requirements of open-source hardware. In this paper, we attempt to provide the documentation, details, and instructions necessary for the construction of an open-source and low-cost super-resolution microscope at a targeted cost of <$15,000.
A community-based ANP-led integrated oncology care model for adults receiving oral anticancer medication-protocol for a pilot study
Authors: Richmond J.P. , Johnston A. , Murphy P.J. , Gillespie P. , Murphy A.W.
Published: February 2022

Oncology has been undergoing a profound transition in the last ten years or more with the increased usage in oral anti-cancer medication (OAM). Approximately 25% of all anti-cancer medication is now designed for oral use and this is likely to increase prospectively. Oral anti-cancer medications have the potential to alleviate capacity issues in cancer treating units as patients receive their treatment at home. There remains however a requirement for safe and efficient assessment and monitoring but this does not necessarily require them to repeatedly attend a hospital day unit. Therefore the opportunity exists to transition this cohort to a community-based setting to be assessed by a specialist such as an Advanced Nurse Practitioner (ANP) in nurse-led clinics. Having an OAM assessment closer to their home would be more convenient to the patient. Furthermore, this could help alleviate hospital capacity issues which were brought into sharp focus with the onset of the COVID-19 pandemic and the use of nurse-led clinics are promoted in the aims of the current healthcare system reform process in Ireland.

Within the context of the Irish healthcare system reform and the COVID-19 pandemic this protocol will outline a collaboration between an Oncology Department in Letterkenny University Hospital in Ireland and the National University of Ireland, Galway aimed to develop and pilot a community-based Advanced Nurse Practitioner-led integrated oncology care model for adults receiving OAM. Phase 1 of this two-phase study commenced in September 2020 and comprised a scoping review, a benchmarking exercise and a qualitative analysis of relevant stakeholders. This protocol paper presents a pilot to be undertaken in phase 2 as OAM care is transitioned to an ANP-led community-based model, which is a radical shift for oncology care in Ireland. The pilot outlined will provide data that will identify potential refinements to the model and address specific uncertainties about a definitive trial.
A novel syndrome caused by the constitutional gain-of-function variant p.Glu1099Lys in NSD2
Authors: Popp Bernt , Brugger Melanie , Poschmann Sibylle , Bartolomaeus Tobias , Radtke Maximilian , Hentschel Julia , Di Donato Nataliya , Rump Andreas , Gburek-Augustat Janina , Graf Elisabeth , Wagner Matias , Lemke Johannes , Meitinger Thomas , Jamra Rami Abou , Strehlow Vincent , Brunet Theresa
Published: February 2022

Purpose

NSD2 dimethylates histone H3 at lysine 36 (H3K36me2) and is located in the Wolf-Hirschhorn syndrome (WHS) region. Recent descriptions delineated loss-of-function (LoF) variants in NSD2 with a distinct disorder. The oncogenic missense variant p.Glu1099Lys occures somatically in leukemia and has a gain-of-function (GoF) effect.

Methods

We describe two unrelated individuals carrying c.3295G>A, p.Glu1099Lys as heterozygous de novo germline variants identified by exome sequencing of blood DNA and subsequently confirmed in two ectodermal tissues. We use omics data from the Cancer Cell Line Encyclopedia to analyze the GoF effect.

Results

Clinically these individuals are characterized by intellectual disability, coarse/ square facial gestalt, abnormalities of the hands and organomegaly. We confirmed increased K36me2 methylation in lines with either NSD2 GoF variants or duplications. Cells with GoF variants showed increased DNA promoter methylation and dysregulated RNA expression, influencing cellular modules involved in white blood cell activation, cell growth and organ development.

Conclusion

NSD2 GoF caused by the missense variant p.Glu1099Lys leads to a novel syndromic phenotype distinct from both the previously described LoF phenotypes. Other variants causing NSD2 hyperactivation or overexpression may cause a similar phenotype. This syndrome should be distinguished from the recently named Rauch-Steindl syndrome caused by NSD2 haploinsufficiency.
Genome-wide study on 72,298 Korean individuals in Korean biobank data for 76 traits identifies hundreds of novel loci
Authors: Nam Kisung , Kim Jangho , Lee Seunggeun
Published: February 2022

Genome-wide association studies (GWAS) on diverse ancestry groups are lacking, resulting in deficits of genetic discoveries and polygenic scores. We conducted GWAS for 76 phenotypes in Korean biobank data, namely Korean Genome and Epidemiology Study (KoGES, n=72,298). Our analysis discovered 2,237 associated loci, including 117 novel associations, many of which replicated in Biobank Japan (BBJ) GWAS. We also applied several up-to-date methods for genetic association tests to increase the power, discovering additional associations that are not identified in simple case-control GWAS. We evaluated genetic pleiotropy to investigate genes associated with multiple traits. Following meta-analysis of 32 phenotypes between KoGES and Biobank Japan (BBJ), we further identified 379 novel associations and demonstrated the improved predictive performance of polygenic risk scores by using the meta-analysis results. The summary statistics of 76 KoGES GWAS phenotypes are publicly available, contributing to a better comprehension of the genetic architecture of the East Asian population.
Quantifying antibody dynamics of severe and non-severe patients with COVID-19
Authors: Ordoñez-Jiménez Fernanda , Blanco-Rodríguez Rodolfo , Almocera Alexis Erich S. , Chinney-Herrera Gustavo , Hernández-Vargas Esteban
Published: February 2022

COVID-19 pandemic is a major public health threat with unanswered questions regarding the role of the immune system in the severity level of the disease. In this paper, based on antibody kinetic data of patients with different disease severity, topological data analysis highlights clear differences in the shape of antibody dynamics between three groups of patients, which were non-severe, severe, and one intermediate case of severity. Subsequently, different mathematical models were developed to quantify the dynamics between the different severity groups. The best model was the one with the lowest media value of Akaike Information Criterion for all groups of patients. Although it has been reported high IgG level in severe patients, our findings suggest that IgG antibodies in severe patients may be less effective than non-severe patients due to early B cell production and early activation of the seroconversion process from IgM to IgG antibody.
Monitoring peripheral hemodynamic response to changes in blood pressure via photoacoustic imaging
Authors: Mantri Yash , Dorobek Tyler R. , Tsujimoto Jason , Penny William F. , Garimella Pranav S. , Jokerst Jesse V.
Published: February 2022

Chronic wounds and amputations are common in chronic kidney disease patients needing hemodialysis (HD). HD is often complicated by drops in blood pressure (BP) called intra-dialytic hypotension. Whether intra-dialytic hypotension is associated with detectable changes in foot perfusion, a risk factor for wound formation and impaired healing remains unknown. Photoacoustic (PA) imaging is ideally suited to study perfusion changes. We scanned the feet of 20 HD and 11 healthy subjects. HD patients were scanned before and after a dialysis session whereas healthy subjects were scanned twice at rest and once after a 10 min exercise period while BP was elevated. Healthy (r=0.70, p<0.0001) and HD subjects (r=0.43, p<0.01) showed a significant correlation between PA intensity and systolic BP. Furthermore, HD cohort showed a significantly reduced PA response to changes in BP compared to the healthy controls (p<0.0001). Hence showing that PA can monitor hemodynamic changes due to changes in BP.
Effectiveness of the third dose of BNT162b2 vaccine on neutralizing Omicron variant in the Japanese population
Authors: Kawasuji Hitoshi , Morinaga Yoshitomo , Tani Hideki , Saga Yumiko , Kaneda Makito , Murai Yushi , Ueno Akitoshi , Miyajima Yuki , Fukui Yasutaka , Nagaoka Kentaro , Ono Chikako , Matsuura Yoshiharu , Niimi Hideki , Yamamoto Yoshihiro
Published: February 2022

Introduction

The vaccine against SARS-CoV-2 provides humoral immunity to fight COVID-19; however, the acquired immunity gradually declines. Booster vaccination restores reduced humoral immunity; however, its effect on newly emerging variants, such as the Omicron variant, is a concern. As the waves of COVID-19 cases and vaccine programs differ between countries, it is necessary to know the domestic effect of the booster.

Methods

Serum samples were obtained from healthcare workers (20-69 years old) in the Pfizer BNT162b2 vaccine program at the Toyama University Hospital 6 months after the second dose (6mA2D, n = 648) and 2 weeks after the third dose (2wA3D, n = 565). The anti-SARS-CoV-2 antibody level was measured, and neutralization against the wild-type and variants (Delta and Omicron) was evaluated using pseudotyped viruses. Data on booster-related events were collected using questionnaires.

Results

The median anti-SARS-CoV-2 antibody was >30.9-fold elevated after the booster (6mA2D, 710.0 U/mL [interquartile range (IQR): 443.0–1068.0 U/mL]; 2wA3D, 21927 U/mL [IQR: 15321.0–>25000.0 U/mL]). Median neutralizing activity using 100-fold sera against wild-type-, Delta-, and Omicron-derived variants was elevated from 84.6%, 36.2%, and 31.2% at 6mA2D to >99.9%, 99.1%, and 94.6% at 2wA3D, respectively. The anti-SARS-CoV-2 antibody levels were significantly elevated in individuals with fever ≥37.5 °C, general fatigue, and myalgia, local swelling, and local hardness.

Conclusion

The booster effect, especially against the Omicron variant, was observed in the Japanese population. These findings contribute to the precise understanding of the efficacy and side effects of the booster and the promotion of vaccine campaigns.
Oxidation-reduction and photophysical properties of isomeric forms of Safranin
Authors: Andersen Eskil M.E. , Wang Hsin , Khoo Joshua S.H. , Cerda Jose , Koder Ronald L.
Published: February 2022

Safranine O is widely used in the bioenergetics community as an indicator dye to determine membrane potentials and as an electron transfer mediator in potentiometric titrations. Here we show that two different commercial preparations of Safranine O contain less than sixty percent by weight of the title compound, with the rest primarily consisting of two closely related safranine isomers. All three major isomer components were isolated using reverse phase HPLC and their structures determined using mass spectrometry and two-dimensional NMR. These Safranines have two-electron midpoint potentials ranging from −272 to −315 mV vs. SHE. We have also investigated the absorption and fluorescence spectra of the compounds and found that they display distinct spectral and photophysical properties. While this mixture may aid in Safranine O’s utility as a mediator compound, membrane potential measurements must take this range of dye potentials into account.
Temporal matches and mismatches between monarch butterfly and milkweed population changes over the past 12,000 years
Authors: Boyle John H. , Strickler Susan , Twyford Alex , Ricono Angela , Powell Adrian , Zhang Jing , Xu Hongxing , Dalgleish Harmony J. , Jander Georg , Agrawal Anurag A. , Puzey Joshua R.
Published: February 2022

In intimate ecological interactions, the interdependency of species may result in correlated demographic histories. For species of conservation concern, understanding the long-term dynamics of such interactions may shed light on the drivers of population decline. Here we address the demographic history of the monarch butterfly, Danaus plexippus, and its dominant host plant, the common milkweed Asclepias syriaca, using broad-scale sampling and genomic inference. Because genetic resources for milkweed have lagged behind those for monarchs, we first release a chromosome-level genome assembly and annotation for common milkweed. Next, we show that despite its enormous geographic range across eastern North America, A. syriaca is best characterized as a single, roughly panmictic population. Using Approximate Bayesian Computation via Random Forests (ABC-RF), a machine learning method for reconstructing demographic histories, we show that both monarchs and milkweed experienced concurrent range expansion during the most recent recession of North American glaciers ∼12,000 years ago. Our data identify an expansion of milkweed during the large-scale clearing of eastern forests (∼200 years ago) but was inconclusive as to expansion or contraction of the monarch butterfly population during this time. Finally, our results indicate that neither species experienced a population contraction over the past 75 years. Thus, the well-documented decline of monarch abundance over the past 40 years is not visible in our genomic dataset, reflecting a possible mismatch of the overwintering census population to effective population size in this species.
A molecular mechanism for high salt taste in Drosophila
Authors: McDowell Sasha A. T. , Stanley Molly , Gordon Michael D.
Published: February 2022

Dietary salt detection and consumption are crucial to maintaining fluid and ionic homeostasis. To optimize salt intake, animals employ salt-dependent activation of multiple taste pathways. Generally, sodium activates attractive taste cells, but attraction is overridden at high salt concentrations by cation non-selective activation of aversive taste cells. In flies, high salt avoidance is driven by both ‘bitter’ taste neurons and a class of glutamatergic ‘high salt’ neurons expressing pickpocket23 (ppk23). Although the cellular basis of salt taste has been described, many of the molecular mechanisms remain elusive. Here, we show that ionotropic receptor 7c (IR7c) is expressed in glutamatergic high salt neurons, where it functions with co-receptors IR76b and IR25a to detect high salt. Misexpression of IR7c in sweet neurons, which endogenously express IR76b and IR25a, confers responsiveness to non-sodium salts, indicating that IR7c is sufficient to convert a sodium-selective receptor to a cation non-selective receptor. Furthermore, the resultant transformation of taste neuron tuning switches potassium chloride from an aversive to an attractive tastant. This research provides insight into the molecular basis of monovalent and divalent salt taste coding and the full repertoire of IRs needed to form a functional salt receptor.
Meta-Analysis of the Functional Neuroimaging Literature with Probabilistic Logic Programming
Authors: Abdallah Majd , Iovene Valentin , Zanitti Gaston , Wassermann Demian
Published: February 2022

Inferring reliable brain-behavior associations requires synthesizing evidence from thousands of functional neuroimaging studies through meta-analysis. However, existing meta-analysis tools are limited to investigating simple neuroscience concepts and expressing a restricted range of questions. Here, we expand the scope of neuroimaging meta-analysis by designing NeuroLang: a domain-specific language to express and test hypotheses using probabilistic first-order logic programming. By leveraging formalisms found at the crossroads of artificial intelligence and knowledge representation, NeuroLang provides the expressivity to address a larger repertoire of hypotheses in a meta-analysis, while seamlessly modelling the uncertainty inherent to neuroimaging data. We demonstrate the language’s capabilities in conducting comprehensive neuroimaging meta-analysis through use-case examples that address questions of structure-function associations. Specifically, we infer the specific functional roles of three canonical brain networks, support the role of the visual word-form area in visuospatial attention, and investigate the heterogeneous organization of the fronto-parietal control network.
Morphometric characters in the taxonomic recognition of the species of Dolichopus pennatus group (Diptera: Dolichopodidae)
Authors: Chursina M.A. , Selivanova O.V.
Published: February 2022

Sexually dimorphic structures (ornaments) on the legs are important diagnostic features for Dolichopus males, whereas females of those males are often morphologically similar and their species diagnostics is difficult. To assessing the relevance and feasibility of setting diagnostic characters for five sister species of the genus Dolichopus Latreille, 1796 (D. argyrotarsis, D. lineaticornis, D. pennatus, D. popularis, D. subpennatus) analysis of morphometric trait was used: comparison of wing shape by methods of geometric morphometry, as well as comparison of the ratios of the leg segments lengths. Comparative analysis of morphometric characters with molecular data made it possible to study the phylogenetic signal of male leg ornaments. It was shown for Dolichopus species, that modifications of the males’ middle legs occurred independently several times in the genus. In addition, the evolutionary pattern in the formation of similar ornaments was also associated with changes in the morphometric features of the legs and wings. Based on wing and legs morphometry, new diagnostic characters were proposed for females of the studied species group.
Eribulin normalizes pancreatic cancer-associated fibroblasts by simulating TGFβ inhibition
Authors: Luong Tiffany , Cukierman Edna
Published: February 2022

Less than 11% of pancreatic cancer patients survive 5-years post-diagnosis. The unique biology of pancreatic cancer includes a significant expansion of its desmoplastic tumor microenvironment, wherein cancer-associated fibroblasts (CAFs) and their self-produced extracellular matrix are key components. CAF functions are both tumor-supportive and tumor-suppressive, while normal fibroblastic cells are solely tumor-suppressive. Knowing that CAF-eliminating drugs are ineffective and can accelerate cancer progression, therapies that “normalize” CAF function are highly pursued. Eribulin is a well-tolerated anti-microtubule drug used to treat a plethora of neoplasias, including advanced/metastatic cancers. Importantly, eribulin can inhibit epithelial to mesenchymal transition via a mechanism akin to blocking pathways induced by transforming growth factor-beta (TGFβ). Notably, canonical TGFβ signaling also plays a pivotal role in CAF activation, which is necessary for the development and maintenance of desmoplasia. Hence, we hypothesized that eribulin could modulate, and perhaps “normalize” CAF function. To test this premise, we used a well-established in vivo-mimetic fibroblastic cell-derived extracellular matrix (CDM) system and gauged the effects of eribulin on human pancreatic CAFs and cancer cells. The pathophysiologic cell-culturing system was also used to query eribulin effects on CDM-regulated cancer cell survival and invasive spread. Results demonstrated that intact CDMs modestly restricted eribulin from obstructing cancer cell growth. Nonetheless, eribulin-treated CAFs generated CDMs that limited cancer cell survival under nutritional stress, similar to reported tumor-suppressive CDMs generated by TGFβ-deficient CAFs. Data from this study support the central proposed premise and suggest that eribulin could be used as a CAF-normalizing drug.