bluuebunny/crossref_metadata_2025 huggingface dataset:
Prestige and financial stability: motivating factors to pursue a doctor of pharmacy degree
Authors: Osmond Dane , Shcherbakova Natalia , Huston Sally
Published: November 2022

Objective

This study aims to identify factors influencing students’ decision to pursue a doctorate in pharmacy (PharmD).

Methods

Focus-group interviews and quantitative surveys were used in sequence to investigate pharmacy students’ motivations. A total of 36 current PharmD students from two US colleges of pharmacy participated in five focus groups. The resulting qualitative findings, along with existing literature, informed the development of a survey questionnaire, which was then administered to two cohorts of first-year pharmacy students at one of the participating colleges.

Key findings

Identified themes include prestige of a doctorate, patient interaction, career versatility, and pharmacy school’s lower intensity vis-à-vis medical school. A total of 110 first-year pharmacy students from a 4-year program (average (SD) age 23 (5); 65% female) completed the survey (98.5% response rate). The order of factors that respondents ranked as important or somewhat important for choosing pharmacy include: financial stability (n = 107 (97%)), prestige of a doctorate degree ((n = 97 (88%)), good work-life balance ((n = 96 (87%)), the opportunity to use critical thinking skills ((n = 93 (85%)), having patient interaction and communication ((n = 91 (83%)), and being in a profession or service ((n = 91 (83%)).

Conclusions

US PharmD students are mainly drawn by job and financial stability, prestige of a doctorate, and a good work-life balance.
Mycoplasmataceae dominate microbial community differences between gut regions in mammals with a simple gut architecture
Authors: Swanson Mark T , Henson Michael W , Handika Heru , Achmadi Anang S , Anita Syahfitri , Rowe Kevin C , Esselstyn Jacob A
Published: November 2022

Faunivorous mammals with simple guts are thought to rely primarily on endogenously produced enzymes to digest food, in part because they lack fermentation chambers for facilitating mutualistic interactions with microbes. However, variation in microbial community composition along the length of the gastrointestinal tract has yet to be assessed in faunivorous species with simple guts. We tested for differences in bacterial taxon abundances and community compositions between the small intestines and colons of 26 individuals representing four species of shrew in the genus Crocidura. We sampled these hosts from a single locality on Sulawesi Island, Indonesia, to control for potential geographic and temporal variation. Bacterial community composition differed significantly between the two gut regions and members of the family Mycoplasmataceae contributed substantially to these differences. Three operational taxonomic units (OTUs) of an unclassified genus in this family were more abundant in the small intestine, whereas 1 OTU of genus Ureaplasma was more abundant in the colon. Species of Ureaplasma encode an enzyme that degrades urea, a metabolic byproduct of protein catabolism. Additionally, a Hafnia–Obesumbacterium OTU, a genus known to produce chitinase in bat gastrointestinal tracts, was also more abundant in the colon compared to the small intestine. The presence of putative chitinase- and urease-producing bacteria in shrew guts suggests mutualisms with microorganisms play a role in facilitating the protein-rich, faunivorous diets of simple gut mammals.
Radiation-driven warping of accretion discs due to X-ray bursts
Authors: Ballantyne D R
Published: November 2022

The outpouring of radiation during an X-ray burst can affect the properties of accretion discs around neutron stars: the corona can cool and collapse, the inner regions can be bled away due to enhanced accretion, and the additional heating will lead to changes in the disc height. In this paper, we investigate whether radiation from bursts can cause the disc to distort through a warping instability. Working in the limit of isotropic viscosity and linear growth, we find that bursts are more likely to drive disc warps when they have larger luminosities and longer durations. Therefore, warps will be most probable during intermediate-duration bursts (IMDBs) and superbursts with evidence for photospheric radius expansion. Further, the development of warps depends on the disc viscosity with larger values of α increasing the likelihood of warp growth. We perform time-dependent evolution calculations of the development of warps during type I bursts and IMDBs. Depending on the initial warp prior to the burst, we find that the burst produces warps at r ≲ 50rg that rapidly grow and decay on second-long time-scales, or ones that grow more slowly and cover a large fraction of the disc. The pulsations of warp at small radii appear to have the properties needed to explain the achromatic fluctuations that have been observed during the tails of some IMDBs. The large-scale, slowly growing warps could account for the large reflection strengths and absorbing column densities inferred late in the 4U 1820-30 and 4U 1636-53 superbursts.
A common origin for the fundamental plane of quiescent and star-forming galaxies in the EAGLE simulations
Authors: de Graaff Anna , Franx Marijn , Bell Eric F , Bezanson Rachel , Schaller Matthieu , Schaye Joop , van der Wel Arjen
Published: November 2022

We use the EAGLE cosmological simulations to perform a comprehensive and systematic analysis of the z = 0.1 fundamental plane (FP), the tight relation between galaxy size, mass, and velocity dispersion. We first measure the total mass and velocity dispersion (including both random and rotational motions) within the effective radius to show that simulated galaxies obey a total mass FP that is very close to the virial relation ($\lt 10{{\ \rm per\ cent}}$ deviation), indicating that the effects of non-homology are weak. When we instead use the stellar mass, we find a strong deviation from the virial plane, which is driven by variations in the dark matter content. The dark matter fraction is a smooth function of the size and stellar mass, and thereby sets the coefficients of the stellar mass FP without substantially increasing the scatter. Hence, both star-forming and quiescent galaxies obey the same FP, with equally low scatter ($0.02\,$dex). We employ simulations with a variable stellar initial mass function (IMF) to show that IMF variations have a modest additional effect on this FP. Moreover, when we use luminosity-weighted mock observations of the size and spatially integrated velocity dispersion, the inferred FP changes only slightly. However, the scatter increases significantly, due to the luminosity-weighting and line-of-sight projection of the velocity dispersions, and measurement uncertainties on the half-light radii. Importantly, we find significant differences between the simulated FP and observations, which likely reflects a systematic difference in the stellar mass distributions. Therefore, we suggest the stellar mass FP offers a simple test for cosmological simulations, requiring minimal post-processing of simulation data.
Incidence proportion and prognosis of leptomeningeal disease among patients with breast vs. non-breast primaries
Authors: Lamba Nayan , Cagney Daniel N , Catalano Paul J , Elhalawani Hesham , Haas-Kogan Daphne A , Wen Patrick Y , Wagle Nikhil , Lin Nancy U , Aizer Ayal A , Tanguturi Shyam
Published: November 2022

Background

Leptomeningeal disease (LMD) is a relatively uncommon manifestation of advanced cancer. Patients with LMD carry a poor prognosis and often decline rapidly, complicating inclusion in clinical trials. Identification of LMD subsets of greater incidence and more favorable prognosis might facilitate dedicated clinical trials in the future. We hypothesized that patients with breast cancer may represent such a population and sought to assess the relative incidence and prognosis of LMD secondary to breast vs. non-breast primaries.

Methods

We identified 2411 patients with intracranial metastases secondary to breast (N = 501) and non-breast (N = 1910) primaries at Brigham and Women’s Hospital/Dana-Farber Cancer Institute between 1996 and 2020, of whom 112 presented with and an additional 161 subsequently developed LMD. A log-rank test and Cox modeling were used to compare outcomes in patients with breast vs. non-breast primaries.

Results

Among patients with newly diagnosed intracranial disease, the incidence proportion of concurrent LMD was 11.4% vs. 2.9% among patients with breast vs. non-breast primaries (P < .001). Development of LMD among initially LMD-naïve patients was also more common among patients with breast vs. non-breast primaries (HR = 1.49 [1.05–2.11], P = .03). Patients with LMD secondary to breast vs. non-breast primaries displayed lower all-cause mortality (HR 0.70 [0.52–0.93], P = .01; median survival: 5.2 vs. 2.4 months, respectively), with a greater numerical difference observed in patients with LMD at intracranial involvement (7.4 vs. 2.6 months, respectively).

Conclusions

Patients with breast cancer and LMD may represent an ideal population for clinical trials given the higher incidence and potentially more favorable prognosis seen in this population.
Dietary energy intake across the menstrual cycle: a narrative review
Authors: Rogan Michaela M , Black Katherine E
Published: November 2022

Females are often underrepresented in the scientific literature, but awareness of the need for female-specific research is increasing. Review articles have been published on the effects of the menstrual cycle on aspects of exercise performance and physiology, yet to date no research has reviewed the effect of menstrual cycle phase on dietary energy intake. Fluctuations in endogenous sex hormones across the menstrual cycle influence a range of physiological processes, including those involved in nutritional status. Observational research typically quantifies female athletes’ nutritional intakes at a single time point; however, this may provide inaccurate information if dietary intake fluctuates across the menstrual cycle. Similarly, this may have implications for interventional research, where dietary intake is often poorly controlled or monitored. This review aimed to synthesize the published literature on dietary energy intakes of naturally menstruating females in various phases of the menstrual cycle. The review critiques the relevant literature in light of recent publications on good practice for female research, explores the impact of the menstrual cycle on energy intake, identifies gaps within the evidence base, and informs future research. Overall, energy intake appears to be lower in the follicular phase compared with the luteal phase, with a particular decrease in the days leading up to and including ovulation. The magnitude of these fluctuations is not yet clearly quantifiable and most likely varies, both between individuals, and from cycle to cycle. This review notes the lack of high-quality research investigating the energy intakes of females across the menstrual cycle, and the very limited data available for female athletes and others who undertake large amounts of physical activity. It also highlights the need for researchers to take into consideration anovulatory cycles and the potential effects of premenstrual disorders on dietary intake.
Intravenous Cyclophosphamide Therapy for Anti-IFN-γ Autoantibody-Associated Talaromyces marneffei Infection
Authors: Zeng Wen , Tang Mengxin , Yang Meiling , Fang Gaoneng , Tang Shudan , Zhang Jianquan
Published: November 2022

High titers of anti-interferon-γ autoantibodies (AIGAs) are an important factor leading to persistent, relapsed, and refractory infections in HIV-negative hosts infected with Talaromyces marneffei (TM). We report 5 patients treated with pulses of high-dose intravenous cyclophosphamide (IVCY) who were followed for 2 years. Before IVCY therapy, all patients had multiple relapses, with a median (interquartile range [IQR]) of 2 (1–3) instances of relapse. The median serum AIGA titers (IQR) were 58 753 (41 203–89 605) ng/mL at diagnosis, 48 189.4 (15 537–83 375) ng/mL before IVCY therapy, and 10 721.2 (5637–13 245) ng/mL at the end of IVCY therapy (P < .05). After 3 months of follow-up, the median AIGA titers (IQR) rose gradually to 21 232.6 (9896–45 626) ng/mL, and to 37 464.2 (19 872–58 321) ng/mL at 24 months (P < .05). Five patients discontinued antimicrobial therapy within 3–12 months after completion of IVCY therapy, but only 1 patient had a relapse. In conclusion, pulses of short-term and high-dose IVCY can effectively reduce AIGA titers.
Children With Cerebral Palsy Show Higher Static—But Not Higher Dynamic—Motor Fatigability in Grip and Pinch Tasks Than Children With Typical Development Do
Authors: Brauers Lieke , Smeets Rob , Feys Peter , Gordon Andrew M , Janssen-Potten Yvonne , Ortibus Els , Feys Hilde , Rameckers Eugene , Klingels Katrijn
Published: November 2022

Objective

The purpose of this study was to investigate differences in static and dynamic motor fatigability during grip and pinch tasks between children with unilateral spastic cerebral palsy (USCP) and children with typical development (TD) and between preferred and nonpreferred hands.

Methods

Fifty-three children with USCP and 53 age-matched children with TD (mean = 11 years 1 month; SD = 3 years 8 months) participated in 30-second maximum exertion sustained and repeated grip and pinch tasks. For sustained tasks, the Static Fatigue Index and the ratio of mean force between the first and last thirds of the curve were calculated. For repeated tasks, the ratio of mean force and the ratio of numbers of peaks between the first and last thirds of the curve were calculated.

Results

Higher Static Fatigue Index scores for grip and pinch were found with USCP in both hands and between hands in both groups. Dynamic motor fatigability showed inconsistent results, with higher levels of fatigability in children with TD than in children with USCP for grip in the ratio of mean force between the first and last thirds of the curve in nonpreferred hands and in the ratio of number of peaks between the first and last thirds of the curve in preferred hands.

Conclusion

Higher motor fatigability in children with USCP than in children with TD was found for static but not dynamic grip and pinch. Underlying mechanisms may play different roles in static and dynamic motor fatigability.

Impact

These results highlight that static motor fatigability in grip and pinch tasks should be part of a comprehensive upper limb assessment and that this could be the target of individualized interventions.
HSC Niche Dynamics in Regeneration, Pre-malignancy, and Cancer: Insights From Mathematical Modeling
Authors: Pedersen Rasmus Kristoffer , Andersen Morten , Skov Vibe , Kjær Lasse , Hasselbalch Hans C , Ottesen Johnny T , Stiehl Thomas
Published: November 2022

The hematopoietic stem cell (HSC) niche is a crucial driver of regeneration and malignancy. Its interaction with hematopoietic and malignant stem cells is highly complex and direct experimental observations are challenging. We here develop a mathematical model which helps relate processes in the niche to measurable changes of stem and non-stem cell counts. HSC attached to the niche are assumed to be quiescent. After detachment HSC become activated and divide or differentiate. To maintain their stemness, the progeny originating from division must reattach to the niche. We use mouse data from literature to parametrize the model. By combining mathematical analysis and computer simulations, we systematically investigate the impact of stem cell proliferation, differentiation, niche attachment, and detachment on clinically relevant scenarios. These include bone marrow transplantation, clonal competition, and eradication of malignant cells. According to our model, sampling of blood or bulk marrow provides only limited information about cellular interactions in the niche and the clonal composition of the stem cell population. Furthermore, we investigate how interference with processes in the stem cell niche could help to increase the effect of low-dose chemotherapy or to improve the homing of genetically engineered cells.
Attitudes, knowledge and practices of traditional snakebite healers in Nepal: implications for prevention and control of snakebite
Authors: Pandey Deb P , Subedi (Pandey) Gita , Sapkota Sunil , Dangol Dharma R , Devkota Naba R
Published: November 2022

Background

Traditional healers are a valuable source of information about community-level treatment of snakebite. Snakebite victims in Nepal depend on traditional healers for treatment, but their practices have not been well-documented.

Methods

This was a cross-sectional study of 50 traditional snakebite healers (TSHs) who were selected using a snowball sampling method representing eight districts and four provinces of Nepal. Data were collected using face-to-face-interviews and semi-structured questionnaires.

Results

About half of the respondents liked to gain knowledge on modern care for snakebite management and nearly all respondents (94%) wished to cooperate closely with the local healthcare system to support snakebite management. People's ingrained faith in traditional healing of snakebite (84%), unaffordable modern care of snakebite (60%) and wishes for early treatment of snakebites (44–48%) were the main causes of their dependency on TSHs. Rauvolfia serpentina, Piper nigrum, Momordica charantia and Tinospora cordifolia were commonly used plants in traditional treatment of snakebite.

Conclusions

Easily accessible and affordable healthcare facilities provided by TSHs, public beliefs in traditional healing and inadequate knowledge of antivenom therapy caused dependency on TSHs. The introduction of snakebite treatment centres in snakebite-prone regions and educational interventions are essential to minimize this kind of dependency and associated deaths and disabilities.
Pediatric Fluoroscopic Follies: Part 2—Journey Through the Lower GI Tract
Authors: Rich Natalie , Sharma Priya G.
Published: November 2022

In part 1 of this series (volume 45, number 2), we explained critical portions of the pediatric upper gastrointestinal fluoroscopic examination and provided an overview of pediatric upper gastrointestinal fluoroscopy to improve confidence and accuracy in diagnosing common and emergent conditions. In this part 2, we discuss the fluoroscopic lower gastrointestinal examination in the pediatric population.
Do Cutting Kinematics Change as Boys Mature? A Longitudinal Cohort Study of High-School Athletes
Authors: Chia Lionel , Myer Gregory D. , Hewett Timothy E. , McKay Marnee J. , Sullivan Justin , Ford Kevin R. , Pappas Evangelos
Published: November 2022

Objective:

Examine longitudinal changes in trunk, hip, and knee kinematics in maturing boys during an unanticipated cutting task.

Design:

Prospective cohort study.

Setting:

Biomechanical laboratory.

Participants:

Forty-two high-school male basketball, volleyball, and soccer athletes.

Assessment of Risk Factors:

Trunk, hip, and knee range-of-motion (RoM), peak angles, and angles at initial contact during an unanticipated 45 degrees sidestep cutting task were estimated using laboratory-based three-dimensional optoelectronic motion capture. Maturation was classified using a modified Pubertal Maturational Observational Scale (PMOS) into prepubertal, midpubertal, or postpubertal stages.

Main Outcome Measures:

Trunk total RoM in frontal, sagittal, and transverse planes; peak trunk flexion, right lateral flexion and right rotation angles; hip total RoM in frontal, sagittal, and transverse planes; hip flexion angle at initial contact; peak hip flexion and adduction angles; knee total RoM in frontal, sagittal, and transverse planes; knee flexion angle at initial contact; peak knee flexion and abduction angles.

Results:

As boys matured, there was a decrease in hip sagittal-plane RoM (49.02 degrees to 43.45 degrees, Benjamini–Hochberg adjusted P = 0.027), hip flexion at initial contact (29.33 degrees to 23.08 degrees, P = 0.018), and peak hip flexion (38.66 degrees to 32.71 degrees, P = 0.046), and an increase in trunk contralateral rotation (17.47 degrees to 25.05 degrees, P = 0.027).

Conclusions:

Maturing male athletes adopted a more erect cutting strategy that is associated with greater knee joint loading. Knee kinematic changes that increase knee joint loading were not observed in this cohort.
Stakeholder perceptions of the efficacy, barriers, and facilitators of telemental health clinical experiences during COVID for nurse practitioner students
Authors: Calloway Susan J. , Hilliard Wanda , Jimenez Rosalinda
Published: November 2022

Background:

Telemental health services grew during the COVID pandemic, resulting in psychiatric–mental health nurse practitioner students obtaining clinical hours through this modality. Although patient outcome data demonstrate the efficacy of telemental health services, data on the efficacy of learning through telehealth clinical experiences are lacking.

Purpose:

To explore perceptions of learning through telehealth clinical experiences by students, preceptors, and faculty and to identify perceived barriers and facilitators to facilitating telehealth clinical experiences.

Methodology:

Mixed-methods exploratory study using web-based, researcher-designed, cross-sectional surveys eliciting perceptions of learning and perceived barriers and facilitators to telemental health clinical experiences sent to current and former PMHNP students and their preceptors of a state university in the southwest along with PMHNP faculty in the National Organization of Nurse Practitioner Faculties. Students and preceptors were offered the option to participate in a semistructured interview.

Results:

Twenty students (35.7%), 22 preceptors (24.7%), and 19 faculty (25.3%) participated in the surveys. Three preceptors and three students volunteered for interviews. Telemental health clinicals were perceived by students as equivalent to or superior to in-person learning. Preceptors rated the teaching/learning environment through telemental health as equivalent or better as compared with in-person clinicals with two exceptions. Faculty-rated greatest barrier to telemental health clinicals was telephone visits because of technology issues.

Conclusions:

Telemental health clinicals can provide a high-quality learning experience for students.

Implications:

Preceptors should be provided with resources for facilitating telemental health clinicals. Ongoing discussions regarding the number of clinical hours recommended through telehealth are needed.
Isavuconazole for the Treatment of Invasive Mold Disease in Solid Organ Transplant Recipients: A Multicenter Study on Efficacy and Safety in Real-life Clinical Practice
Authors: Fernández-Ruiz Mario , Bodro Marta , Gutiérrez Martín Isabel , Rodriguez-Álvarez Regino , Ruiz-Ruigómez María , Sabé Núria , López-Viñau Teresa , Valerio Maricela , Illaro Aitziber , Fortún Jesús , Salto-Alejandre Sonsoles , Cordero Elisa , Fariñas María del Carmen , Muñoz Patricia , Vidal Elisa , Carratalà Jordi , Goikoetxea Josune , Ramos-Martínez Antonio , Moreno Asunción , Aguado José María ,   SOTIS Study Group
Published: November 2022

Background.

Isavuconazole has theoretical advantages over other mold-active triazoles for the treatment of invasive aspergillosis and mucormycosis after solid organ transplantation (SOT). The available clinical experience, nevertheless, is scarce.

Methods.

We performed a retrospective study including all adult SOT recipients with proven or probable invasive mold disease (IMD) that received isavuconazole for ≥24 h as first-line or salvage therapy at 10 Spanish centers between September 2017 and November 2021. The primary efficacy outcome was clinical response (complete or partial resolution of attributable symptoms and findings) by weeks 6 and 12. Safety outcomes included the rates of treatment-emergent adverse events and premature isavuconazole discontinuation.

Results.

We included 81 SOT recipients that received isavuconazole for a median of 58.0 days because of invasive aspergillosis (n = 71) or mucormycosis (n = 10). Isavuconazole was used as first-line (72.8%) or salvage therapy due because of previous treatment-emergent toxicity (11.1%) or refractory IMD (7.4%). Combination therapy was common (37.0%), mainly with an echinocandin or liposomal amphotericin B. Clinical response by weeks 6 and 12 was achieved in 53.1% and 54.3% of patients, respectively, and was more likely when isavuconazole was administered as first-line single-agent therapy. At least 1 treatment-emergent adverse event occurred in 17.3% of patients, and 6.2% required premature discontinuation. Daily tacrolimus dose was reduced in two-thirds of patients by a median of 50.0%, although tacrolimus levels remained stable throughout the first month of therapy.

Conclusions.

Isavuconazole is a safe therapeutic option for IMD in SOT recipients, with efficacy comparable to other patient groups.
Humoral Response to the Fourth BNT162b2 Vaccination and Link Between the Fourth Dose, Omicron Infection, and Disease Severity in Renal Transplant Recipients
Authors: Hod Tammy , Ben-David Aharon , Mor Eytan , Olmer Liraz , Halperin Rebecca , Indenbaum Victoria , Beckerman Pazit , Doolman Ram , Asraf Keren , Atari Nofar , Benjamini Ohad , Lustig Yaniv , Grossman Ehud , Mandelboim Michal , Rahav Galia
Published: November 2022

Background.

The effectiveness of the fourth BNT162b2 vaccination in reducing the rate and severity of coronavirus disease 2019 (COVID-19) caused by the Omicron variant in renal transplant recipients (RTRs) is unknown.

Methods.

Interviews were conducted with 447 RTRs regarding the status and timing of the fourth vaccination, prior vaccinations, and preceding COVID-19 infection. RTRs with polymerase chain reaction–confirmed COVID-19 infection from December 1, 2021, to the end of March 2022 were considered to have been infected with the Omicron variant and were interviewed to determine their disease severity. In a subgroup of 74 RTRs, the humoral response to the fourth dose was analyzed. In 30 RTRs, microneutralization assays were performed to reveal the humoral response to wild-type, Delta, and Omicron variant isolates before and after the fourth dose.

Results.

Of 447 RTRs, 144 (32.2%) were infected with the Omicron variant, with 71 (49.3%) of the infected RTRs having received the fourth vaccine dose. RTRs who did not receive the fourth dose before the infection had more serious illness. In a subgroup of 74 RTRs, the fourth dose elicited a positive humoral response in 94.6% (70/74), with a significant increase in geometric mean titer for receptor-binding domain immunoglobulin G and neutralizing antibodies (P < 0.001). The humoral responses to the Omicron variant before and after the fourth dose were significantly lower than the responses to the wild-type and the Delta variants.

Conclusions.

Overall, the fourth BNT162b2 dose was effective in reducing the rate and severity of Omicron disease in RTRs, despite the reduced humoral response to the variant.
The purinergic receptors 2X3 on spiral ganglion neurons enhance the medial olivocochlear reflex in mice after long-term moderate noise exposure
Authors: Yin Dongming , Zhang Tianyu , Dai Peidong
Published: November 2022

Our purpose was to study the expression of purinergic receptors 2X2 (P2X2) and purinergic receptors 2X3 (P2X3) in spiral ganglion neurons (SGNs), the afferent nerves of medial olivocochlear (MOC) reflex, after long-term moderate noise exposure, and its relationship with the enhancement of MOC reflex. Mice were exposed a moderate broadband noise for 4 weeks consecutively. Then mouse hearing functions, including threshold auditory brainstem responses, distortion-product otoacoustic emissions, and MOC reflex, were evaluated and the expression of P2X2 and P2X3 on SGNs were assessed by cochlear immunofluorescence. AF-353 was injected before each noise exposure. Four weeks later, mice were also tested for hearing functions and expression of P2X2 and P2X3 on SGNs. The long-term moderate noise strengthened MOC reflex, and AF-353 reduced it in mice and P2X3 expression on SGNs increased after long-term moderate noise exposure, and AF-353 can downregulate it. The P2X3 on SGNs of mice increased after long-term moderate noise exposure, and the upregulation of it mediated the enhancement of MOC reflex.
More than static: altered dynamic functional connectivity of primary visual cortex in the comitant exotropia patients
Authors: Chen Juan , Chen Wan Yun , Huang Xin
Published: November 2022

Previous neuroimaging studies have demonstrated that comitant exotropia (CE) patients exhibit dysfunction in various visual cortical areas. However, whether the CE patients showed abnormal dynamic functional connectivity (dFC) in primary visual cortex (V1) changes remains unknown. A total of 36 CE patients (25 males and 11 females) and 36 well-matched healthy control subjects (HCs) were enrolled in the study. The dFC with sliding window method was applied to investigate the dynamic functional connectivity changes in primary visual cortex (V1). Compared with HCs, CE patients had decreased dFC values between left V1 and right fusiform (Fus), right lingual (LING), left orbital medial frontal gyrus, left Fus, left calcarine and left precuneus (PreCUN). Meanwhile, CE patients had decreased dFC values between right V1 and left cerebelum_6 (CER_6), right lingual and left inferior occipital gyrus. Our study demonstrates that CE patients showed altered dFC within visual network and V1-default mode network, which might indicate the decreased variability FC values in the primary visual cortex in CE patients.
Spermidine inhibits high glucose-induced endoplasmic reticulum stress in HT22 cells by upregulation of growth differentiation factor 11
Authors: Liao Zhou-Zan , Deng Qi , Xiao Fan , Xie Ming , Tang Xiao-Qing
Published: November 2022

Hyperglycemia-induced neuronal endoplasmic reticulum (ER) stress is particularly important for the pathogenesis of diabetic encephalopathy. Spermidine (Spd) has neuroprotection in several nervous system diseases. Our current study to explore the potential protective role of Spd in hyperglycemia-induced neuronal ER stress and the underlying mechanisms. HT22 cells were treated with high glucose (HG) to establish an in-vitro model of hyperglycemia toxicity. The HT22 cells’ activity was tested by cell counting kit-8 assay. RNA interference technology was used to silence the expression of growth differentiation factor 11 (GDF11) in HT22 cells. The GDF11 expression levels of mRNA were assessed using reverse transcription-PCR (RT-PCR). Western blotting analysis was applied to evaluate the expressions of GRP78 and cleaved caspase-12. Spd markedly abolished HG-exerted decline in cell viability as well as upregulations of GRP78 and cleaved caspase-12 in HT22 cells, indicating the protection of Spd against HG-induced neurotoxicity and ER stress. Furthermore, we showed that Spd upregulated the expression of GDF11 in HG-exposed HT22 cells. While, silenced GDF11 expression by RNA interference reversed the protective effects of Spd on HG-elicited neurotoxicity and ER stress in HT22 cells. These results indicated that Spd prevents HG-induced neurotoxicity and ER stress through upregulation of GDF11. Our findings identify Spd as a potential treatment for diabetic encephalopathy as well as ER stress-related neurologic diseases.
A Longitudinal Seroepidemiology Study to Evaluate Antibody Response to SARS-CoV-2 Virus and Vaccination in Children in Calgary, Canada from July 2020 to April 2022
Authors: Doucette Emily J. , Gray Joslyn , Fonseca Kevin , Charlton Carmen , Kanji Jamil N. , Tipples Graham , Kuhn Susan , Dunn Jessica , Sayers Payton , Symonds Nicola , Wu Guosong , Freedman Stephen B , Kellner James D. ,   the Alberta COVID-19 Childhood Cohort (AB3C) Study Team
Published: November 2022

Background

Measurement of SARS-CoV-2 antibody seropositivity is important to accurately understand exposure to infection and/or vaccination in specific populations.

Methods

Children with or without prior SARS-CoV-2 infections, was enrolled in Calgary, Canada in 2020. Venous blood was sampled 4 times from July 2020 to April 2022 for SARS-CoV-2 nucleocapsid and spike antibodies. Demographic and clinical information was obtained including SARS-CoV-2 testing results and vaccination records.

Results

1035 children were enrolled and 88.9% completed all 4 visits; median age 9 years (IQR: 5,13); 519 (50.1%) female; and 815 (78.7%) Caucasian. Before enrollment, 118 (11.4%) had confirmed or probable SARS-CoV-2. By April 2022, 39.5% of previously uninfected participants had a SARS-CoV-2 infection. Nucleocapsid antibody seropositivity declined to 16.4% after more than 200 days after diagnosis. Spike antibodies remained elevated in 93.6% of unvaccinated children after more than 200 days after diagnosis. By April 2022, 408 (95.6%) children 12 years and older had received 2 or more vaccine doses, and 241 (61.6%) 5 to 11 year-old children had received 2 vaccine doses. At that time, all 685 vaccinated children had spike antibodies, compared with 94/176 (53.4%) of unvaccinated children.

Conclusions

In our population, after the first peak of Omicron variant infections and introduction of COVID-19 vaccines for children, all vaccinated children had SARS-CoV-2 spike antibodies, in contrast to 53.4% of unvaccinated children. It is not yet known whether a high level of seropositivity at a point in time indicates sustained population-level protection against SARS-CoV-2 transmission or severe COVID-19 outcomes in children.

By April 2022, all vaccinated children with or without acquired SARS-CoV-2 infections had spike antibodies, compared with just over one-half of unvaccinated children. It’s not known whether overall seropositivity level in a population indicates sustained protection against severe COVID-19 outcomes.
Online internal speech decoding from single neurons in a human participant
Authors: Wandelt Sarah K. , Bjånes David A. , Pejsa Kelsie , Lee Brian , Liu Charles , Andersen Richard A.
Published: November 2022

Speech brain-machine interfaces (BMI’s) translate brain signals into words or audio outputs, enabling communication for people having lost their speech abilities due to diseases or injury. While important advances in vocalized, attempted, and mimed speech decoding have been achieved, results for internal speech decoding are sparse, and have yet to achieve high functionality. Notably, it is still unclear from which brain areas internal speech can be decoded. In this work, a tetraplegic participant with implanted microelectrode arrays located in the supramarginal gyrus (SMG) and primary somatosensory cortex (S1) performed internal and vocalized speech of six words and two pseudowords. We found robust internal speech decoding from SMG single neuron activity, achieving up to 91% classification accuracy during an online task (chance level 12.5%). Evidence of shared neural representations between internal speech, word reading, and vocalized speech processes were found. SMG represented words in different languages (English/ Spanish) as well as pseudowords, providing evidence for phonetic encoding. Furthermore, our decoder achieved high classification with multiple internal speech strategies (auditory imagination/ visual imagination). Activity in S1 was modulated by vocalized but not internal speech, suggesting no articulator movements of the vocal tract occurred during internal speech production. This works represents the first proof-of-concept for a high-performance internal speech BMI.
Accuracy and Precision of 3D Optical Imaging for Body Composition and their Associations to Metabolic Markers by Age, BMI, and Ethnicity
Authors: Wong Michael C. , Bennett Jonathan P. , Quon Brandon , Leong Lambert T. , Tian Isaac Y. , Liu Yong E. , Kelly Nisa N. , McCarthy Cassidy , Chow Dominic , Pujades Sergi , Garber Andrea K. , Maskarinec Gertraud , Heymsfield Steven B. , Shepherd John A.
Published: November 2022

Background

Recent three-dimensional optical (3DO) imaging advancements have provided a more accessible, affordable, and self-operating opportunities for assessing body composition. 3DO is accurate and precise compared to clinical measures measured by dual-energy X-ray absorptiometry (DXA) in diverse study samples. However, the accuracy and precision of an overall 3DO body composition model in specific subgroups is unknown. Therefore, this study aimed to evaluate 3DO’s accuracy and precision by subgroups of age, body mass index (BMI), and ethnicity/race.

Methods

A cross-sectional analysis was performed using the Shape Up! Adults study. Each participant received duplicate 3DO and DXA scans. 3DO meshes were digitally registered and reposed using Meshcapade to standardize the vertices and pose. Principal component analysis was performed on the registered 3DO meshes to orthogonalize and reduce the dimensionality of the data. The resulting principal components estimated DXA whole-body and regional body composition using stepwise forward linear regression with five-fold cross-validation. Duplicate 3DO and DXA scans were used for test-retest precision. Student’s t-test was performed between 3DO and DXA by subgroup to determine significant differences. One-way ANOVA determined if intra-group precision had significant differences. P-value < 0.05 was considered statistically significant.

Results

Six hundred thirty-four participants (females = 346) had completed the study at the time of the analysis. 3DO total fat mass (FM) and fat-free mass (FFM) in the entire sample achieved R2s of 0.94 and 0.92 with RMSEs of 2.91 kg and 2.76 kg, respectively, in females and similarly in males. 3DO total FM and FFM achieved a %CV (RMSE) of 1.76% (0.44 kg) and 1.97% (0.44 kg), while DXA had a %CV (RMSE) of 0.98% (0.24 kg) and 0.59% (0.27 kg), respectively, in females and similarly in males. There were no mean differences by age group (p-value > 0.068). However, there were mean differences for underweight females, NHOPI females and males, and Asian and black females (p-value < 0.038). There were no significant differences among the subgroups for precision (p-value > 0.109).

Conclusion

A single 3DO body composition model derived from a highly-stratified dataset performed well against DXA with minimal differences detected for accuracy and precision. Adjustments to specific subgroups may be warranted to improve the accuracy in those that had significant differences. Nevertheless, 3DO produced accurate and precise body composition estimates that can be used on diverse populations.
Augmenting vaccine efficacy against delta variant with ‘Mycobacterium-w’ mediated modulation of NK-ADCC and TLR-MYD88 pathways
Authors: Jaiswal Sarita Rani , Saifullah Ashraf , Arunachalam Jaganath , Lakhchaura Rohit , Tailor Dhanir , Mehta Anupama , Bhagawati Gitali , Aiyer Hemamalini , Biswas Subhrajit , Khamar Bakulesh , Malhotra Sanjay V. , Chakrabarti Suparno
Published: November 2022

Mycobacterium-w (Mw), was shown to boost adaptive natural killer (ANK) cells and protect against COVID-19 during the first wave of the pandemic. As a follow-up of the trial, 50 healthcare workers (HCW) who had received Mw in September 2020 and subsequently received at least one dose of ChAdOx1 nCoV-19 vaccine (Mw+ChAdOx1 group) were monitored for symptomatic COVID-19, during a major outbreak with the delta variant of SARS-CoV-2 (April-June, 2021), along with 201 HCW receiving both doses of the vaccine without Mw (ChAdOx1 group). Despite 48% having received just a single dose of the vaccine in Mw+ChAdOx1 group, only 2 had mild COVID-19, compared to 36 infections in the ChAdOx1 group (HR-0.46, p=0.009). Transcriptomic studies revealed an enhanced adaptive NK cell-dependent ADCC in the Mw+ChAdOx1 group, along with downregulation of TLR2-MYD88 pathway and concomitant attenuation of downstream inflammatory pathways. This might have resulted in robust protection during the pandemic with the delta variant.
Analysis of 21 appendices from children with multisystem inflammatory syndrome compared to specimens of acute appendicitis – a new insight into MIS-C pathology
Authors: Okarska-Napierała Magdalena , Woźniak Weronika , Mańdziuk Joanna , Ludwikowska Kamila Maria , Feleszko Wojciech , Grzybowski Jakub , Panczyk Mariusz , Berdej-Szczot Elżbieta , Zaryczański Janusz , Górnicka Barbara , Szenborn Leszek , Kuchar Ernest
Published: November 2022

Background & Aims

Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019, commonly involving the gastrointestinal tract. Some children with MIS-C undergo appendectomy before the final diagnosis. There are several hypotheses explaining pathomechanism of MIS-C, with the central role of the viral antigen persistence in the gut, associated with lymphocyte exhaustion and immune system dysregulation. We aimed to examine appendectomy specimens obtained from MIS-C patients and analyze the pathological features of the disease and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in the appendix.

Methods

In this cross-sectional study we included 21 children with MIS-C who underwent appendectomy before the final diagnosis. MIS-C patients were recruited from the Polish national registry of inflammatory syndromes in children. The control group included 21 sex- and age-matched children with acute appendicitis (AA) unrelated to SARS-CoV-2 infection. Histological evaluation involved hematoxylin and eosin staining and immunohistochemical identification of lymphocyte subpopulations, programmed cell death protein 1, and SARS-CoV-2 nucleocapsid antigen.

Results

Appendices of MIS-C patients lacked neutrophilic infiltrate of muscularis propria typical for AA (14 vs 95%, p<0.001). The proportion of CD20+to CD5+cells was higher in patients with MIS-C (p 0.04), as well as the proportion of CD4+to CD8+(p <0.001). We found no proof of SARS-CoV-2 antigen presence, nor lymphocyte exhaustion, in the appendices of MIS-C patients.

Conclusions

Our findings describe pathomorphological features of the appendix in MIS-C and argue against the central role of SARS-CoV-2 persistence in the gut and concomitant lymphocyte exhaustion as the major triggers of MIS-C.
Real-time forecasting the trajectory of monkeypox outbreaks at the national and global levels, July – October 2022
Authors: Bleichrodt Amanda , Dahal Sushma , Maloney Kevin , Casanova Lisa , Luo Ruiyan , Chowell Gerardo
Published: November 2022

Background

Beginning May 7, 2022, multiple nations reported an unprecedented surge in monkeypox cases. Unlike past outbreaks, differences in affected populations, transmission mode, and clinical characteristics have been noted. With the existing uncertainties of the outbreak, real-time short-term forecasting can guide and evaluate the effectiveness of public health measures.

Methods

We obtained publicly available data on confirmed weekly cases of monkeypox at the global level and for seven countries (with the highest burden of disease at the time this study was initiated) from the Our World in Data (OWID) GitHub repository and CDC website. We generated short-term forecasts of new cases of monkeypox across the study areas using an ensemble n-sub-epidemic modeling framework based on weekly cases using 10-week calibration periods. We report and assess the weekly forecasts with quantified uncertainty from the top-ranked, second-ranked, and ensemble sub-epidemic models. Overall, we conducted 324 weekly sequential 4-week ahead forecasts across the models from the week of July 28th, 2022, to the week of October 13th, 2022.

Results

The last 10 of 12 forecasting periods (starting the week of August 11th, 2022), show either a plateauing or declining trend of monkeypox cases for all models and areas of study. According to our latest 4-week ahead forecast from the top-ranked model, a total of 6232 (95% PI: 487.8, 12468.0) cases could be added globally from the week of 10/20/2022 to the week of 11/10/2022. At the country level, the top-ranked model predicts that the United States will report the highest cumulative number of new cases for the 4-week forecasts (median based on OWID data: 1806 (95% PI: 0.0, 5544.5)). The top-ranked and weighted ensemble models outperformed all other models in short-term forecasts.

Conclusions

Our top-ranked model consistently predicted a decreasing trend in monkeypox cases on the global and country-specific scale during the last ten sequential forecasting periods. Our findings reflect the potential impact of increased immunity, and behavioral modification among high-risk populations.
Prevalence of cirrhotic cardiomyopathy according to different diagnostic criteria. Alterations in ultrasonographic parameters of both left and right ventricles before and after stress
Authors: Karagiannakis Dimitrios S , Stefanaki Katerina , Anastasiadis George , Voulgaris Theodoros , Vlachogiannakos Jiannis
Published: November 2022

Background

Prevalence of cirrhotic cardiomyopathy (CC) remains controversial. Several guidelines have been proposed for its assessment.

Aim

To estimate the frequency of CC by using all of the proposed diagnostic criteria, to describe the whole spectrum of cardiac alterations and investigate the role of stress in unmasking latent cases of CC.

Methods

Ninety consecutive patients were recruited. CC was evaluated by using the Montreal, the 2009 and 2019 criteria. Dobutamine stress test was also performed.

Results

LVDD was identified in 72(80%), 36(40%) and 10(11.1%) patients based on the above criteria, respectively. None of the patients had right ventricular systolic dysfunction, neither at rest, nor after stress. Stress test revealed left systolic dysfunction in 4(4.5%) patients. According to 2019 criteria, presence of LVDD was not associated with gender, etiology, or staging of liver disease. Patients with LVDD had longer QTc (p=0.002), larger LAvol (p=0.0001), lower TAPSE(s) (p=0.012), lower SRV(s) (p=0.0001) and lower ΔCI (p=0.009) compared to those without. Patients with Child-B/C had longer QTc (p=0.004), higher BNP (p=0.016), higher E/e’ (p=0.0001) and higher E/e’(s) (p=0.003), compared to Child-A patients. A significant correlation was demonstrated between Child-Pugh score and E/e’ (p=0.0001), or E/e’(s) (p=0.002).

Conclusions

In accordance with the recent guidelines the prevalence of CC seems to be lower. LVDD is the predominant feature of CC and aggravates along with the severity of liver disease. After dobutamine administration several sonographic variables exacerbate, particularly in Child-B/C patients, indicating a potential higher risk for clinical heart failure during stressful invasive interventions.
Modeling post-holiday surge in COVID-19 cases in Pennsylvania counties
Authors: Ren Benny , Hwang Wei-Ting
Published: November 2022

COVID-19 arrived in the United States in early 2020, with cases quickly being reported in many states including Pennsylvania. Many statistical models have been proposed to understand the trends of the COVID-19 pandemic and factors associated with increasing cases. While Poisson regression is a natural choice to model case counts, this approach fails to account for correlation due to spatial locations. Being a contagious disease and often spreading through community infections, the number of COVID-19 cases are inevitably spatially correlated as locations neighboring counties with a high COVID-19 case count are more likely to have a high case count. In this analysis, we combine generalized estimating equations for Poisson regression, a popular method for analyzing correlated data, with a semivariogram, to model daily COVID-19 case counts in 67 Pennsylvania counties between March 20, 2020 to January 23, 2021 in order to study infection dynamics during the beginning of the pandemic. We use a semivariogram that describes the spatial correlation as a function of the distance between two counties as the working correlation. We further incorporate a zero-inflated model in our spatial GEE to accommodate excess zeros in reported cases due to logistical challenges associated with disease monitoring. By modeling time-varying holiday covariates, we estimated the effect of holiday timing on case count. Our analysis showed that the incidence rate ratio was significantly greater than one, 6-8 days after a holiday suggesting a surge in COVID-19 cases approximately one week after a holiday.