bluuebunny/crossref_metadata_2025 huggingface dataset:
External Validation of the Revised Pretransplant Assessment of Mortality Score in Allogeneic Hematopoietic Cell Transplantation: A Cohort Study
Authors: Fattinger Nicolas , Roth Jan A. , Baldomero Helen , Stolz Daiana , Medinger Michael , Heim Dominik , Tamm Michael , Halter Jörg P. , Passweg Jakob R. , Kleber Martina
Published: March 2022

Pretransplant risk scores such as the revised Pretransplant Assessment of Mortality (rPAM) score help to predict outcome of patients receiving allogeneic hematopoietic cell transplantation (allo-HCT). Since the rPAM has not been validated externally in a heterogeneous patient population with different diseases, we aimed to validate the rPAM score in a real-world cohort of allo-HCT patients. A total of 429 patients were included receiving their first allo-HCT from 2008 to 2015. The predictive capacity of the rPAM score for 4-year overall survival (OS), nonrelapse mortality (NRM), and cumulative incidence of relapse (CIR) after allo-HCT was evaluated. Moreover, we evaluated the impact of the rPAM score for OS and used uni- and multivariable analyses to identify patient- and transplant-related predictors for OS. In rPAM score categories of <17, 17–23, 24–30, and >30, the OS probability at 4 years differed significantly with 61%, 36%, 26%, and 10%, respectively (P < 0.0001). In contrast to CIR, the NRM increased significantly in patients with higher rPAM scores (P < 0.001). Regarding the OS, the rPAM score had an area under the receiver operating characteristics curve of 0.676 (95% confidence interval [CI], 0.625-0.727) at 4 years. In the multivariable analysis, the rPAM score was associated with OS—independently of conditioning regimens (adjusted hazard ratio per 1-unit increase, 1.10; 95% CI, 1.06-1.10; P < 0.001). Additionally, forced expiratory volume in 1 second and the disease risk index were the components of the rPAM significantly associated with outcome. In our large real-world cohort with extended follow-up, the rPAM score was validated as an independent predictor of OS in patients with hematologic disorders undergoing allo-HCT.
Association Between Risk Factors and Readmission for Patients With Atrial Fibrillation Treated With Catheter Ablation
Authors: Risom Signe Stelling , Thygesen Lau Caspar , Rasmussen Trine Bernholdt , Borregaard Britt , Nørgaard Marianne Wetendorff , Mols Rikke , Christensen Anne Vinggaard , Thorup Charlotte Brun , Thrysoee Lars , Juel Knud , Ekholm Ola , Berg Selina Kikkenborg
Published: March 2022

Background

Because of high readmission rates for patients treated with ablation for atrial fibrillation (AF), there is great value in nurses knowing which risk factors make the largest contribution to readmission.

Objective

The aims of this study were to (1) describe potential risk factors at discharge and (2) describe the associations of risk factors with readmission from 60 days to 1 year after discharge.

Methods

Data from a national cross-sectional survey exploring patient-reported outcomes were used in conjunction with data from national health registers. This study included patients who had an ablation for AF during a single calendar year. The Hospital Anxiety and Depression Scale and questions on risk factors were included. Sociodemographic and clinical data were collected through registers, and readmissions were examined at 1 year.

Results

In total, 929 of 1320 (response rate, 70%) eligible patients treated with ablation for AF completed the survey. One year after ablation, there were 333 (36%) acute readmissions for AF and 401 (43%) planned readmissions for AF. Readmissions were associated with ischemic heart disease, anxiety, and depression.

Conclusion

High observed readmission rates were associated with risk factors that included anxiety and depression. Postablation care should address these risk factors.
Cardiac arrest and coronavirus disease 2019
Authors: Baldi Enrico , Cortegiani Andrea , Savastano Simone
Published: March 2022

Purpose of review

The impact of the coronavirus disease 2019 (COVID-19) on the cardiovascular system has been highlighted since the very first weeks after the severe acute respiratory syndrome coronavirus 2 identification. We reviewed the influence of COVID-19 pandemic on cardiac arrest, both considering those occurred out of the hospital (OHCA) and in the hospital (IHCA).

Recent findings

An increase in OHCA incidence occurred in different countries, especially in those regions most burdened by the COVID-19, as this seems to be bounded to the pandemic trend. A change of OHCA patients’ characteristics, with an increase of the OHCA occurred at home, a decrease in bystander cardiopulmonary resuscitation and automated external defibrillator use before Emergency Medical Service (EMS) arrival and an increase in non-shockable rhythms, have been highlighted. A dramatic drop in the OHCA patients’ survival was pointed out in almost all the countries, regardless of the high or low-incidence of COVID-19 cases. Concerning IHCA, a reduction in survival was highlighted in patients with COVID-19 who sustained a cardiac arrest.

Cardiac arrest occurrence and survival were deeply affected by the pandemic. Informative campaigns to the population to call EMS in case of need and the re-allocation of the prehospital resources basing on the pandemic trend are needed to improve survival.
The future of resuscitation education
Authors: Bray Janet E. , Greif Robert , Morley Peter
Published: March 2022

Purpose of review

The purpose of this review is to provide an update for critical care clinicians and providers on the recent developments in patient and healthcare professional (HCP) resuscitation education.

Recent findings

The family members of patients at high-risk of cardiac arrest need to be provided with access to basic life support (BLS) training. Many low-cost methods are now available to provide BLS training beyond attending a traditional BLS instructor-led cardiopulmonary resuscitation (CPR) class. Hybrid-blended learning formats provide new opportunities to receive individualized CPR-training in a flexible and convenient format. HCPs’ participation in accredited advanced life support courses improves patient outcomes. Monitoring HCPs exposure to resuscitation and supplementing with frequent simulation is recommended. Training should include human factors and nontechnical skills. Volunteering for first responder programs when off-duty provides a great opportunity for HCP's to improve out-of-hospital cardiac arrest survival and increase exposure to resuscitation.

Frequent resuscitation education and training is critical to improving cardiac arrest patient outcomes. Recent evidence shows the effectiveness of technological developments to improve access to training and outcomes.
Cardiac output monitoring – invasive and noninvasive
Authors: Arya Virendra K. , Al-Moustadi Waiel , Dutta Vikas
Published: March 2022

Purpose of review

The purpose of this article is to review various contemporary cardiac output (CO) measurement technologies available and their utility in critically ill patients.

Recent findings

CO measurement devices can be invasive, minimally invasive, or noninvasive depending upon their method of CO measurement. All devices have pros and cons, with pulmonary artery catheter (PAC) being the gold standard. The invasive techniques are more accurate; however, their invasiveness can cause more complications. The noninvasive devices predict CO via mathematical modeling with several assumptions and are thus prone to errors in clinical situations. Recently, PAC has made a comeback into clinical practice especially in cardiac intensive care units (ICUs). Critical care echocardiography (CCE) is an upcoming tool that not only provides CO but also helps in differential diagnosis. Lack of proper training and nonavailability of equipment are the main hindrances to the wide adoption of CCE.

PAC thermodilution for CO measurement is still gold standard and most suitable in patients with cardiac pathology and with experienced user. CCE offers an alternative to thermodilution and is suitable for all ICUs; however, structural training is required.
Endohepatology – current status
Authors: Edelson Jerome C. , Mitchell Natalie E. , Rockey Don C.
Published: March 2022

Purpose of review

This article discusses the most recent studies regarding the emerging field of endohepatology – the use of diagnostic and therapeutic endoscopic tools for the management of patients with liver disease and portal hypertension.

Recent findings

New research has shown that liver biopsy specimens obtained by each Endoscopic ultrasound (EUS)-guidance, the percutaneous approach, and the transjugular approach contained sufficient portal triads to adequately analyzed by experienced pathologists – suggesting that any of these routes of liver biopsy is clinically acceptable; further, all had similar rates of adverse events. An initial prospective study showed that EUS guided portal pressure measurement was safe, effective, and accurate. A recent metanalysis showed that EUS-guided cyanoacrylate injection and coil embolization was statistically more efficacious and with less complications than EUS guided cyanoacrylate injection and EUS guided coil injection alone, suggesting that combination therapy appears to be the preferred approach for gastric varices (GV) bleeding. A prospective study evaluating focal liver lesions showed that the use of artificial intelligence had up to 100% sensitivity and 81% specificity for identifying malignant focal liver lesions.

EUS guided liver biopsy is safe and enables accurate diagnosis of underlying liver disease. EUS guided portal pressure measurement is also safe and is accurate. Combination therapy of EUS guided cyanoacrylate injection and coil embolization is more efficacious and has less complications than injection or coil therapy alone when used for GV bleeding. Artificial intelligence is highly sensitive and specific when used in conjunction with EUS in the diagnosis of malignant focal liver lesions. Endohepatology is a rapidly expanding field with great potential.
Small dense low-density lipoprotein particles: clinically relevant?
Authors: Krauss Ronald M.
Published: March 2022

Purpose of review

Levels of small, dense low-density lipoprotein (LDL) (sdLDL) particles determined by several analytic procedures have been associated with risk of atherosclerotic cardiovascular disease (ASCVD). This review focuses on the clinical significance of sdLDL measurement.

Recent findings

Results of multiple prospective studies have supported earlier evidence that higher levels of sdLDL are significantly associated with greater ASCVD risk, in many cases independent of other lipid and ASCVD risk factors as well as levels of larger LDL particles. A number of properties of sdLDL vs. larger LDL, including reduced LDL receptor affinity and prolonged plasma residence time as well as greater oxidative susceptibility and affinity for arterial proteoglycans, are consistent with their heightened atherogenic potential. Nevertheless, determination of the extent to which sdLDL can preferentially impact ASCVD risk compared with other apoprotein B-containing lipoproteins has been confounded by their metabolic interrelationships and statistical collinearity, as well as differences in analytic procedures and definitions of sdLDL.

A growing body of data points to sdLDL concentration as a significant determinant of ASCVD risk. Although future studies should be aimed at determining the clinical benefit of reducing sdLDL levels, there is sufficient evidence to warrant consideration of sdLDL measurement in assessing and managing risk of cardiovascular disease.

Video abstract

https://www.dropbox.com/s/lioohr2ead7yx2p/zoom_0.mp4?dl=0
Addition of “Septal Window” to Lower Blepharoplasty for the Management of Fat of the Lower Eyelids
Authors: Tran Bao Ngoc N. , Luthringer Margaret , Reed Laura , Asaadi Mokhtar
Published: March 2022

Background

The most common reason for dissatisfaction and reoperation in lower blepharoplasty patients is persistent bulging of the lateral fat pad. This compartment contributes the most to fat herniation and yet is the most commonly overlooked. The addition of a septal window, a small opening of the septum on the most prominent part of the lateral fat compartment, helps with precise removal of lateral fat and allows for additional fat excision after septal reset without disrupting the arcuate expansion.

Methods

Our lower blepharoplasty approach includes 1) a subcilliary incision; 2) aggressive lateral fat excision through a septal window; 3) central and medial fat excision, transposition, and septal reset; 4) canthopexy; 5) orbicularis oculi muscle suspension; and 6) no dissection of orbicularis oculi medially and no skin resected medially to avoid lid retraction. We performed a retrospective review of all lower blepharoplasty cases by a single surgeon over 10 years. Demographics and operative outcomes were queried.

Results

There were 224 cases, 90% were women with a mean age of 58.2 years. The most common postoperative occurrences were eyelid edema, malar edema, and chemosis, all of which were self-limiting. Two patients needed additional removal of lateral fat of their lower eyelids.

Two patients had lid retraction, one of which had a previous facial nerve palsy and the other did not have a canthopexy and developed transient unilateral lid retraction that resolved with conservative treatment. Resumption of full activities and exercises at 6 weeks was typical.

Conclusion

The septal window facilitates aggressive resection of the lateral fat pad and additional fat excision after septal reset to create a smooth lid-cheek junction. In our practice, it is a critical component of a successful lower blepharoplasty.
Short-Segment Drilling Guides for the Management Comminuted Mandibular Fractures
Authors: Zhuang Hai , Zhu Bowen , Bu Shoushan
Published: March 2022

Treatment of a severely comminuted mandibular fracture is challenging. This technical note describes a novel office-based workflow, combining virtual surgery planning with short-segment drilling guides. The authors reduced the comminuted mandibular fractures via virtual surgery planning. Then, the reconstructed mandible model was printed using an in-house 3D printer. Next, the reconstruction plate was preformed according to the shape of the mandibular model surface, and the position of the screw hole in the mandibular surface was determined. Finally, hand-made short-segment drilling guides for screw position transfer were fabricated with temporary resin. During the operation, the authors reset the guides for the drill to make screw holes as planned. After the hole was drilled, the pre-bent plate was applied to the mandible. The fracture was expected to be reduced, when tightening the screws. in our workflow, by using short and simple operative procedures, the authors were able to achieve precise reduction and reduce the operation time.
Botulinum Toxin Injections as an Adjunct to Surgical Lip Repositioning For Gummy Smile Treatment
Authors: Queiroz Thallita Pereira , Luvizuto Eloá Rodrigues , Marques Daniela Oliveira , Santos Vinícius Bastos Porto , Corbi Sâmara Cruz Tfaile , dos Santos Pamela Leticia
Published: March 2022

Background:

An attractive smile depends on the proper proportion and arrangement of lip, teeth gingiva scaffold. The ideal smile is the exposure of the entire length of maxillary teeth with 1 mm gingiva. A gingival display exceeding 3 mm is unpleasant and termed ‘‘gummy smile (GS).’’ Lip repositioning is a simple surgical procedure intended to minimize the gingival display by removing a strip of mucosa and shortening the vestibular depth. Botulinum toxin injecting overactive muscles with measured quantities results in a reduction of muscle activity, relaxing the lip muscles and decreasing upward pull on the lip. There are some contraindications: patients with short lips and gingival exposures less than 3 mm.

Purpose:

This case report describes the successful management of GS of a young man.

Case Report:

The procedures were performed and these techniques resulted in shortened vestibule and restricted the muscle pull of the elevator muscles of the lip, reducing gingival display when the patient smiles. Surgical lip repositioning can be a minimally invasive alternative to orthognathic surgery. Botulinum Toxin injections can be a useful adjunct to enhance the esthetics and improve patient satisfaction, being a more conservative and immediate nonsurgical treatment modality available.

Conclusions:

In this way, the clinical case report demonstrated that lip repositioning surgery combined to botulinum toxin injections promising outcomes in the GS correction. The effect showed a marked reduction in gingival display at the 4-years follow-up.
Intramuscular Fat Graft Results in Lower Retention but Similar Quality Compared with Subcutaneous Counterpart
Authors: Jin Shengyang , Liu Wei , Jiang Haiyue
Published: March 2022

The adipose tissue has been injected into both subcutaneous and intramuscular planes for volume augmentation. However, the differences in their outcomes have yet to be fully elucidated. To investigate the differences of intramuscular and subcutaneous graft outcome, adipose tissue was harvested from the inguinal fat pad of mice and then placed into the quadriceps femoris or the subcutaneous plane, respectively. At 8 weeks, the graft outcome was evaluated by gross weight assessment, hema-toxylin and eosin staining, and CD31 staining. The authors found out that though the intramuscular graft had lower weight retention than the subcutaneous graft, the histologic quality and vascularity were similar between the intramuscular and subcutaneous graft. To summarize, the muscle is a feasible plane for fat grafting clinically. While performing intramuscular fat grafting, moderate overcorrec-tion may be necessary to achieve satisfactory results.
Sevoflurane diminishes neurogenesis and promotes ferroptosis in embryonic prefrontal cortex via inhibiting nuclear factor-erythroid 2–related factor 2 expression
Authors: Song Ruixue , Wang Rong , Shen Ziying , Chu Haichen
Published: March 2022

Objective

Prenatal sevoflurane exposure may pose neurotoxicity to embryonic brain development and lead to cognitive dysfunction in offspring, but the underlying mechanism is still unclear. We aimed to investigate whether sevoflurane could cause neurogenesis abnormality and ferroptosis in embryonic prefrontal cortex (PFC) and to identify the role of nuclear factor-erythroid 2–related factor 2 (Nrf2) in the sevoflurane-related neurotoxicity.

Methods

We used the rodents and primary neural stem cells to examine whether sevoflurane impacted proliferation, differentiation, ferroptosis and apoptosis in the neural stem cells of embryonic PFC. In addition, the expression of Nrf2 and the intensity of reactive oxygen species (ROS) were also assessed to explore the underlying molecular mechanism.

Results

Our results showed that sevoflurane exposure in third trimester could lead to neurogenesis inhibition and ferroptosis in-vivo embryonic PFC, with little influence on apoptosis. Moreover, a significant decrease in the expression of Nrf2 as well as an increase in ROS accumulation were also found in neural stem cells after sevoflurane anesthesia.

Conclusion

We conclude that Nrf2-related neurogenesis inhibition and ferroptosis are a central mechanism contributing to sevoflurane-induced neurotoxicity in embryonic brain. The results of the present study are the first to demonstrate that ferroptosis and the expression of Nrf2 are involved in sevoflurane-related neurotoxicity in embryonic brain, which provides new vision for consideration in anesthesia-associated neurological abnormalities.
II. Observations on the diurnal variation of the magnetic needle, at the Whale Fish Islands, Davi's Strait.
Authors: Foster Henry
Published: March 2022

Previous to leaving England in the spring of 1824, I had determined upon making a series of observations on the daily variation of the magnetic needle, during our stay, at the different places which might be visited by the Expedition. Accordingly, soon after our arrival at the Whale Fish Islands, for the purpose of transhipping the stores from the Transport which had accompanied us thus far; the instrument for observing the diurnal variation was landed, and placed on a pedestal in a small octagonal observatory.
IV. Abstract of the daily variation of the magnetic needle No.2
Authors: Foster Henry
Published: March 2022

Tables showing the diurnal change in the intensity of the magnetic horizontal needle at Port Bowen, from February 15th to May 31st, 1825: the time specified in the different columns being that, during which, the needle performed 60 vibrations at every hour of the above interval.
VI. Observations on the diurnal changes in the position of the horizontal needle, under a reduced directive power, at Port Bowen, 1825.
Authors: Foster Henry
Published: March 2022

The daily variation of the horizontal needle is a subject which has, for nearly a century, attracted the attention of several accurate observers, whose object was principally limited to determining the hour of the day, when its amount was the greatest, and the times of the needle's successive easterly and westerly motions.
Thiomicrorhabdus heinhorstiae sp. nov. and Thiomicrorhabdus cannonii sp. nov.: novel sulphur-oxidizing chemolithoautotrophs isolated from the chemocline of Hospital Hole, an anchialine sinkhole in Spring Hill, Florida, USA
Authors: Updegraff Tatum , Schiff-Clark Grayson , Gossett Hunter , Parsi Sheila , Peterson Rebecca , Whittaker Robert , Dennison Clare , Davis Madison , Bray James , Boden Rich , Scott Kathleen
Published: March 2022

Two sulphur-oxidizing, chemolithoautotrophic aerobes were isolated from the chemocline of an anchialine sinkhole located within the Weeki Wachee River of Florida. Gram-stain-negative cells of both strains were motile, chemotactic rods. Phylogenetic analysis of the 16S rRNA gene and predicted amino acid sequences of ribosomal proteins, average nucleotide identities, and alignment fractions suggest the strains HH1T and HH3T represent novel species belonging to the genus

Thiomicrorhabdus

. The genome G+C fraction of HH1T is 47.8 mol% with a genome length of 2.61 Mb, whereas HH3T has a G+C fraction of 52.4 mol% and 2.49 Mb genome length. Major fatty acids of the two strains included C16 : 1, C18 : 1 and C16 : 0, with the addition of C10:0 3-OH in HH1T and C12 : 0 in HH3T. Chemolithoautotrophic growth of both strains was supported by elemental sulphur, sulphide, tetrathionate, and thiosulphate, and HH1T was also able to use molecular hydrogen. Neither strain was capable of heterotrophic growth or use of nitrate as a terminal electron acceptor. Strain HH1T grew from pH 6.5 to 8.5, with an optimum of pH 7.4, whereas strain HH3T grew from pH 6 to 8 with an optimum of pH 7.5. Growth was observed between 15–35 °C with optima of 32.8 °C for HH1T and 32 °C for HH3T. HH1T grew in media with [NaCl] 80–689 mM, with an optimum of 400 mM, while HH3T grew at 80–517 mM, with an optimum of 80 mM. The name Thiomicrorhabdus heinhorstiae sp. nov. is proposed, and the type strain is HH1T (=DSM 111584T=ATCC TSD-240T). The name Thiomicrorhabdus cannonii sp. nov is proposed, and the type strain is HH3T (=DSM 111593T=ATCC TSD-241T).
Impact of long-term COVID on workers: a systematic review protocol
Authors: do Prado Camila Bruneli , Emerick Giselly Storch , Cevolani Pires Luciana Bicalho , Salaroli Luciane Bresciani
Published: March 2022

Introduction

Part of the patients infected by COVID-19 have at least one lasting sequel of the disease and may be framed in the concept of long Covid. These sequelae can compromise the quality of life, increase dependence on other people for personal care, impair the performance of activities of daily living, thus compromising work activities and harming the health of the worker. This protocol aims to critically synthesize the scientific evidence on the effects of Covid-19 among workers and its impact on their health status and professional life.

Method

Searches will be performed in MEDLINE via PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, LILACS and Epistemonikos. Included studies will be those that report the prevalence of long-term signs and symptoms in workers and/or the impact on their health status and work performance, which may be associated with Covid-19 infection. Data extraction will be conducted by 3 reviewers independently. For data synthesis, a results report will be carried out, based on the main outcome of this study.

Discussion

This review will provide evidence to support health surveillance to help decision makers (i.e. healthcare providers, stakeholders and governments) regarding long-term Covid.
Disturbance by soil mixing decreases microbial richness and supports homogenizing community assembly processes
Authors: West Jaimie R. , Whitman Thea
Published: March 2022

The spatial heterogeneity of soil’s microhabitats warrants the study of ecological patterns and community assembly processes in the context of community coalescence, or the combining and restructuring of communities and their environment. By mixing soil at various frequencies in a 16-week lab incubation, we explored the effects of mixing disturbance on soil bacterial richness, community composition, and community assembly processes. We hypothesized that well-mixed soil would harbor less richness, dominated by homogenizing dispersal and homogeneous selection. Using 16S rRNA gene sequencing, we inferred ecological processes, estimated richness and differential abundance, calculated compositional dissimilarity, and constructed co-occurrence networks. Findings supported our hypotheses, with >20% decrease in soil bacterial richness in well-mixed soil. While soil mixing resulted in increasingly dissimilar communities compared to unmixed soil (Bray-Curtis dissimilarity; 0.75 vs. 0.25), well-mixed soil communities were increasingly self-similar. Our results imply that vast soil diversity may be attributed to the unmixed and spatially heterogeneous nature of soil, and also provide insight into soil communities following coalescence events. By isolating and better understanding the effect of spatial heterogeneity and dysconnectivity on soil microbial communities, we may better extrapolate how anthropogenic disturbances, such as climate change or land use change, may affect broad soil functions.

One sentence summary

Soil mixing decreases bacterial richness as several taxa dominate the community, providing evidence for homogenizing community assembly processes.
Self-navigating the “Island of Reil”: a systematic review of real-time fMRI neurofeedback training of insula activity
Authors: Zhang Yuan , Zhang Qiong , Becker Benjamin , Kendrick Keith M. , Yao Shuxia
Published: March 2022

Real-time fMRI (rtfMRI) neurofeedback (NF) is a novel noninvasive technique that permits individuals to voluntarily control brain activity or connectivity, with demonstrated feasibility in experimental and therapeutic applications. The crucial role of the insula in emotional and salience processing makes it a popular target in rtfMRI studies although there is no systematic review of their efficacy. To promote our understanding of mechanisms underlying insula regulation and thereby facilitate therapeutic translation, the present review identified 22 preclinical and clinical studies and found that rtfMRI-based NF training is efficient for modulating insula activity (> 86%) and its associated behavioral and neural changes. Based on findings, continuous feedback for multiple training sessions, specific strategies validated before application, inclusion of a practice session, and choosing appropriate localization strategies are suggested as guidelines. We also recommend standardization of training protocol design, statistical analyses and results reports for future studies. In summary, the present review informs both fundamental research and therapeutic translation of NF training as an intervention in mental disorders, particularly those with insula dysfunction.
Enzyme-Responsive Nanoparticles for the Targeted Delivery of an MMP Inhibitor to the Heart post Myocardial Infarction
Authors: Sullivan Holly L. , Liang Yifei , Worthington Kendra , Luo Colin , Gianneschi Nathan C. , Christman Karen L.
Published: March 2022

In this paper, we describe block copolymer amphiphiles consisting of a hydrophilic matrix metalloproteinase (MMP) peptide substrate, and a hydrophobic small molecule MMP inhibitor PD166793 for the treatment of acute myocardial infarction. These resulting drug loaded peptide-polymer amphiphiles (PPAs) assemble in aqueous solution to yield drug loaded micellar nanoparticles. Following minimally invasive intravenous injection, these nanoparticles preferentially exit the vasculature and are physically trapped at the infarcted region of the heart due to MMP-induced peptide cleavage and aggregation. This MMP directed active assembly prevents the material from leaking out into the blood stream, enabling long-term retention. Further, we show that the conjugated MMP inhibitor (PD166793) is inactivated in the core of the micelles and can be released upon the action of proteases and esterases, leading to MMP inhibition. This work establishes a promising targeted nanoparticle platform for delivering small molecule therapeutics to the heart.
Is virtual care the new normal? Evidence supporting Covid-19’s durable transformation on healthcare delivery
Authors: Mandal Soumik , Wiesenfeld Batia , Mann Devin M. , Lawrence Katharine , Chunara Rumi , Testa Paul A. , Nov Oded
Published: March 2022

Objective

Despite the surge of telemedicine use during the early stages of the coronavirus-19 (COVID-19) pandemic, research has not evaluated the extent to which the growth of telemedicine has been sustained during recurring pandemic waves. This study provides data on the long-term durability of video-based telemedicine visits and their impact on urgent and non-urgent healthcare delivery from one large health system in New York City.

Materials and Methods

Electronic health record (EHR) data of patients between January 1st, 2020 and November 30th, 2021 were used to conduct the analyses and longitudinal comparisons of telemedicine or in-person visit volumes. Patients’ diagnosis data were used to differentiate COVID-19 suspected visits from non-COVID-19 ones while comparing the visit types.

Results

While COVID-19 prompted an increase in telemedicine visits and a simultaneous decline in in-person clinic visits, telemedicine use has stabilized since then for both COVID-19 and non-COVID suspected visits. For COVID-19 suspected visits, utilization of virtual urgent care facilities is higher than the trend. The data further suggests that virtual healthcare delivery supplements, rather than replaces, in-person care.

Discussion

The COVID-19 pandemic has transformed the use of telemedicine as a means of healthcare delivery, and the data presented here suggests that this is an enduring transformation.

Conclusion

Telemedicine use increased with the surge of infection cases during the pandemic, but evidence suggests that it will persist after the pandemic, especially for younger patients, for both urgent and non-urgent care. These findings have implications for the healthcare delivery system, insurers and policymakers.
The Adaptive Olfactory Measure of Threshold (ArOMa-T): A rapid test of olfactory function
Authors: Weir Elisabeth M. , Hannum Mackenzie E. , Reed Danielle R. , Joseph Paule V. , Munger Steven D. , Hayes John E. , Gerkin Richard C.
Published: March 2022

Many widely-used psychophysical olfactory tests have limitations that can create barriers to adoption outside research settings. For example, tests that measure the ability to identify odors may confound sensory performance with memory recall, verbal ability, and past experience with the odor. Conversely, typical threshold-based tests avoid these issues, but are labor intensive. Additionally, many commercially-available olfactory tests are slow and may require a trained administrator, making them impractical for use in a short wellness visit or other broad clinical assessment. We tested the performance of the Adaptive Olfactory Measure of Threshold (ArOMa-T) – a novel odor detection threshold test that employs an adaptive Bayesian algorithm paired with a disposable odorant – delivery card – in a non-clinical sample of individuals (n=534) at the 2021 Twins Day Festival in Twinsburg, OH. Participants successfully completed the test in under 3 min with a false alarm rate of 9.6% and a test-retest reliability of 0.61. Odor detection thresholds differed by sex (∼3.2-fold lower for females) and age (∼8.7-fold lower for the youngest versus the oldest age group), consistent with prior studies. In an exploratory analysis, we failed to observe evidence of detection threshold differences between participants who reported a history of COVID-19 and matched controls who did not. We also found evidence for broad-sense heritability of odor detection thresholds. Together, these data indicate the ArOMa-T can determine odor detection thresholds. The ArOMa-T may be particularly valuable in clinical or field settings where rapid and portable assessment of olfactory function is needed.
Chromosomal microarray analyses from 5,778 patients with neurodevelopmental disorders and congenital anomalies in Brazil
Authors: Krepischi Ana C. V. , Villela Darine , da Costa Silvia Souza , Mazzonetto Patricia C. , Migliavacca Michele P. , Milanezi Fernanda , Santos Juliana G. , Guarischi-Sousa Rodrigo , Campana Gustavo , Kok Fernando , Schlesinger David , Kitajima Joao Paulo , Campagnari Francine , Vianna-Morgante Angela M. , Pearson Peter L. , Rosenberg Carla
Published: March 2022

Chromosomal microarray analysis (CMA) has been recommended and practiced routinely since 2010 in USA and Europe as the first-tier cytogenetic test for patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies. However, in Brazil, the use of CMA is still limited, due to its high cost and complexity of the combination of private and public health systems. Although the country has one of the world largest single payer public healthcare system, nearly all patients referred for CMA come from the private sector. This reflects on the small number of CMA studies in Brazilian cohorts. This study is by far the largest Brazilian cohort (n=5,788) studied by CMA and results from a joint collaboration formed by the University of Sao Paulo and three private genetic diagnostic centers to investigate the genetic bases of neurodevelopmental disorders and congenital abnormalities. It is common practice to investigate the inheritance of VUS; however, our results indicate an extremely low cost-benefit of this approach, and strongly suggest that in cases of limited budget, investigation of the parents of VUS carriers using CMA should not be prioritized. Another aspect discussed is the classification of variants of low penetrance, once CNV classification is mostly designed to Mendelian or highly-penetrant variants.
Blood transcriptomic biomarkers of alcohol consumption and cardiovascular disease risk factors: the Framingham Heart Study
Authors: Ma Jiantao , Huang Allen , Yan Kaiyu , Sun Xianbang , Joehanes Roby , Huan Tianxiao , Levy Daniel , Liu Chunyu
Published: March 2022

Background

The relations of alcohol consumption and gene expression remain to be elucidated in large study samples.

Objectives

To study the relationship between alcohol consumption, gene expression, and cardiovascular disease (CVD) risk factors.

Methods

We performed cross-sectional association analysis of whole blood derived gene expression levels with alcohol consumption in 5,531 Framingham Heart Study (FHS) participants (mean age 55 years; 54% women) by splitting the sample into a discovery sample and a replication sample (2:1 ratio) using independent pedigrees. We also examined the cross-sectional association of alcohol-associated genes with three CVD risk factors: obesity, hypertension, and diabetes. Linear mixed models or generalized estimation equations were used to quantify associations accounting for familial relationship and multiple covariates.

Results

We identified 25 alcohol-associated genes (false discovery rate < 0.05 in the discovery sample and Bonferroni corrected P < 0.05 in the replication sample). We further showed cross-sectional associations of 16 alcohol-associated genes with obesity, nine genes with hypertension, and eight genes with diabetes (all P < 0.002). For example, we observed decrease in expression of PROK2 (β = -0.0018; 95%CI: -0.0021, -0.0007; P = 6.5e-5) and PAX5 (β = -0.0014; 95%CI: -0.0021, -0.0007; P = 6.5e-5) per 1 g/day increase in alcohol consumption. Consistent with our previous observation on the inverse association of alcohol consumption with obesity and positive association of alcohol consumption with hypertension, we found that PROK2 was positively associated with obesity (OR = 1.42; 95%CI: 1.17, 1.72; P = 4.5e-4) and PAX5 was negatively associated with hypertension (OR = 0.73; 95%CI: 0.59, 0.89; P = 1.6e-3). We also observed that alcohol consumption was positively associated with expression of ABCA13 (β = 0.0012; 95%CI: 0.0007, 0.0017; P = 1.3e-6) and ABCA13 was positively associated with diabetes (OR = 2.57; 95%CI: 1.73, 3.84; P = 3.5e-06); this finding, however, was inconsistent with our observation on the inverse association between alcohol consumption and diabetes.

Conclusions

We observed that alcohol consumption was associated with whole blood expression levels of 25 genes in middle aged to older adults in the FHS. In addition, complex relationships may exist between alcohol-associated genes and CVD risk factors.
Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury
Authors: Palikuqi Brisa , Rispal Jeremie , Vaka Deedepya , Boffelli Dario , Klein Ophir
Published: March 2022

The intestinal epithelium undergoes continuous renewal and has an exceptional capacity to regenerate after injury. Maintenance and proliferation of intestinal stem cells (ISCs) is regulated by their surrounding niche, largely through Wnt signaling. However, it remains undetermined which niche cells produce signals during different injury states, and the role of endothelial cells (ECs) as a component of the ISC niche during homeostasis and after injury has been underappreciated. Here, we show that lymphatic endothelial cells (LECs) reside in proximity to crypt epithelial cells and secrete molecules that support epithelial renewal and repair. The LECs are an essential source of Wnt signaling in the small intestine, as loss of LEC-derived Rspo3 leads to a lower number of stem and progenitor cells and hinders recovery after cytotoxic injury. Together, our findings identify LECs as an essential niche component for optimal intestinal recovery after cytotoxic injury.
Molecular Dynamic Investigation of H5N1 Influenza Virus Dual H274Y-I222K Mutation Resistance to Peramivir
Authors: Buthelezi Ndumiso M. , Mtambo Sphamandla E. , Amoako Daniel G. , Somboro Anou M. , Yakubu Elliasu , Khan Rene B. , Mhlongo Ndumiso N. , Kumalo Hezekiel M.
Published: March 2022

In light of the rapid rise of an influenza pandemic, the constant genetic mutations of H5N1 influenza viruses pose a threat. Mutations at the sialic site are often responsible for multiple drug resistance. To design effective new inhibitors, it is necessary to undertake research into the mechanism of resistance of influenza viruses and their rapid mutations. The molecular dynamic simulation technique has been an instrumental tool in understanding how proteins function from an atomic perspective. A thorough investigation has not been conducted using molecular dynamics to examine the impact of these mutations (I222K, H274Y, and H274Y-I222K) on Peramivir. This study investigates the effects of I222K, H274Y, H274Y-I222K substitution on the neuraminidase–Peramivir complex and identifies responsible residues for complex conformations. The mutations caused distorted Peramivir orientation in the enzyme active site, which affected the inhibitor’s binding. In the presence of various mutations, interaction between protein and ligand became less thermodynamically favorable. We observed the following trend in binding free energy difference: WT<I222<H274Y<H274Y-I222K. As a result of the thermodynamic instability of the mutant complexes, Peramivir’s potency is reduced due to impaired binding interactions. Wild type complex displays thermodynamic stability and strong protein-ligand interactions due to their high total energy contributions and low residue flexibility. Based on the energy decomposition analysis, Arg117, Arg224, and Arg292 contributed the largest residual energy for the binding of Peramivir to wild type and mutants. These residues are thought to play a key role in the formation of the binding pocket between Peramivir and neuraminidase. This study provides a basis for investigating the effects of other mutations on Peramivir’s efficacy against the H5N1 virus.
The ZuCo Benchmark on Cross-Subject Reading Task Classification with EEG and Eye-Tracking Data
Authors: Hollenstein Nora , Tröndle Marius , Plomecka Martyna , Kiegeland Samuel , Özyurt Yilmazcan , Jäger Lena A. , Langer Nicolas
Published: March 2022

We present a new machine learning benchmark for reading task classification with the goal of advancing EEG and eye-tracking research at the intersection between computational language processing and cognitive neuroscience. The benchmark task consists of a cross-subject classification to distinguish between two reading paradigms: normal reading and task-specific reading. The data for the benchmark is based on the Zurich Cognitive Language Processing Corpus (ZuCo 2.0), which provides simultaneous eye-tracking and EEG signals from natural reading. The training dataset is publicly available, and we present a newly recorded hidden testset. We provide multiple solid baseline methods for this task and discuss future improvements. We release our code and provide an easy-to-use interface to evaluate new approaches with an accompanying public leaderboard:www.zuco-benchmark.com.

Highlights

We present a new machine learning benchmark for reading task classification with the goal of advancing EEG and eye-tracking research.

We provide an interface to evaluate new approaches with an accompanying public leaderboard.

The benchmark task consists of a cross-subject classification to distinguish between two reading paradigms: normal reading and task-specific reading.

The data is based on the Zurich Cognitive Language Processing Corpus of simultaneous eye-tracking and EEG signals from natural reading.
The choice of the objective function in flux balance analysis is crucial for predicting replicative lifespans in yeast
Authors: Schnitzer Barbara , Österberg Linnea , Cvijovic Marija
Published: March 2022

Flux balance analysis (FBA) is a powerful tool to study genome-scale models of the cellular metabolism, based on finding the optimal flux distributions over the network. While the objective function is crucial for the outcome, its choice, even though motivated by evolutionary arguments, has not been directly connected to related measures. Here, we used an available multi-scale mathematical model of yeast replicative ageing, integrating cellular metabolism, nutrient sensing and damage accumulation, to systematically test the effect of commonly used objective functions on features of replicative ageing in budding yeast, such as the number of cell divisions and the corresponding time between divisions. The simulations confirmed that assuming maximal growth is essential for reaching realistic lifespans. The usage of the parsimonious solution or the additional maximisation of a growth-independent energy cost can improve lifespan predictions, explained by either increased respiratory activity using resources otherwise allocated to cellular growth or by enhancing antioxidative activity, specifically in early life. Our work provides a new perspective on choosing the objective function in FBA by connecting it to replicative ageing.
Mental Workload Classification of Oceanauts from EEG Data Using Multiclass Support Vector Machines
Authors: Liu Xiaoguang , Shi Lu , Ye Cong , Li Yangyang , Wang Jing
Published: March 2022

This manuscript has been withdrawn by bioRxiv as it was submitted and made public without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author
Idetification of CACNA1B (p.K567R) mutation responsible for familiar AVNRT
Authors: Luo Rong , Cao Xin , Zheng Chenqing , Huang Jichang , Liu Mingjiang , He Tao , Jiang Panpan , Yang Xu , Yang Zhenglin , Wu Xiushan , Li Xiaoping
Published: March 2022

Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of paroxysmal supraventricular tachycardia (PSVT). The exact cause of AVNRT has not yet been found. However, an increasing number of reports suggest that AVNRT is hereditary, but no precise pathogenic gene has been found so far. In our study, we found that a point mutation of CACNA1B (p.K567R) which encoded the α1 subunit of N-type calcium channel (Cav 2.2), was cosegregated with AVNRT in one family. Previous research showed that overexpression and point mutations of human CACNA1B in zebrafish embryos may be related to abnormal heart rate. Telemetric ECG recordings showed that rats with a CACNA1B point mutation displayed sporadic supraventricular tachycardia and altered QRS complex morphology. In addition, the CACNA1B (p.K567R) rats presented a double path phenomenon and AVNRT induction by intracardiac electrophysiological examination. Indexes of heart rate variance in CACNA1B mutation rats showed an in cardiac sympathetic activity and an imbalance of cardiac sympathetic and parasympathetic activity. Single-cell RNA sequencing indicated that the number of neurons in the superior cervical ganglion (SCG) of mutant rats was higher than in wild-type (WT) rats, accompanied by an increased expression of CACNA1B. Functional enrichment in SCG proteomics suggests that point mutant rats have abnormalities in synaptic function and ion transport, which could lead to the release of neurotransmitters. This could affect the cardiac autonomic neural activity and lead to an imbalance in sympathetic and parasympathetic activity and the subsequent occurrence of AVNRT. Our findings indicate that CACNA1B (p.K567R) is the pathogenic gene of AVNRT in familial AVNRT and confirm that CACNA1B is the first definitive AVNRT pathogenic gene that has been discovered.