bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the role of the Kölliker–Fuse nucleus in breathing variability by mathematical modelling
Authors: John S. R. , Barnett W. H. , Abdala A. P. L. , Zoccal D. B. , Rubin J. E. , Molkov Y. I.
Published: December 2023

The Kölliker–Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnoea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apnoeas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupnoeic as well as RTT‐like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT‐like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late‐expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing.

image

Key points

The Kölliker–Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation.

Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modelling to explore different dynamical regimes of KF activity and their compatibility with experimental observations.

By analysing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT‐like respiratory patterns and proposes potential KF local circuit organizations.

Two models are presented that simulate both normal breathing and RTT‐like breathing patterns.

These models provide testable hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.
Mountains of research: Where and whom high‐altitude physiology has overlooked
Authors: Tremblay Joshua C.
Published: December 2023

High altitude is a natural setting in which to study human acclimatization and adaptation. Here, I identify where and in whom high‐altitude physiology research has occurred. There has been a mismatch between countries with large high‐altitude populations vs. where high‐altitude research has been conducted. From 1970 to 2020, 83% of high‐altitude physiology research took place in just seven countries: Nepal, China, USA, Peru, India, Bolivia and Italy. Collectively, these countries account for only 35% of the global population living above 2500 m. Furthermore, high‐altitude physiology research has predominantly studied low‐altitude residents visiting high altitude and female participants are under‐represented. Accordingly, the included populations are not necessarily a proportional representation of high‐altitude residents. Here, I discuss how this influences our understanding of high‐altitude adaptation. Finally, I highlight past initiatives to increase diversity in high‐altitude research. By identifying the broad gaps in high‐altitude physiology research, I propose exciting, inclusive opportunities to study human high‐altitude physiology.

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Youths Are Less Susceptible to Exercise-Induced Muscle Damage Than Adults: A Systematic Review With Meta-Analysis
Authors: Fernandes John F.T. , Hayes Lawrence D. , Dingley Amelia F. , Moeskops Sylvia , Oliver Jon L. , Arede Jorge , Twist Craig , Wilson Laura J.
Published: December 2023

Purpose: This meta-analysis aimed to (1) provide a comparison of peak changes in indirect markers of exercise-induced muscle damage (EIMD) in youths versus adults and (2) determine if the involved limb moderated this effect. Method: Studies were eligible for inclusion if they (1) provided a human youth versus adult comparison; (2) provided data on muscle strength, soreness, or creatine kinase markers beyond ≥24 hours; and (3) did not provide a recovery treatment. Effect sizes (ES) were presented alongside 95% confidence intervals. Results: EIMD exhibited larger effects on adults than in youths for muscle strength (ES = −2.01; P < .001), muscle soreness (ES = −1.52; P < .001), and creatine kinase (ES = −1.98; P < .001). The random effects meta-regression indicated that the effects of upper- and lower-limb exercise in youths and adults were significant for muscle soreness (coefficient estimate = 1.11; P < .001) but not for muscle strength or creatine kinase (P > .05). As such, the between-group effects for muscle soreness (ES = −2.10 vs −1.03; P < .05) were greater in the upper than lower limbs. Conclusion: The magnitude of EIMD in youths is substantially less than in their adult counterparts, and this effect is greater in upper than lower limbs for muscle soreness. These findings help guide practitioners who may be concerned about the potential impact of EIMD when training youth athletes.
Exceptionally preserved stomach contents of a young tyrannosaurid reveal an ontogenetic dietary shift in an iconic extinct predator
Authors: Therrien François , Zelenitsky Darla K. , Tanaka Kohei , Voris Jared T. , Erickson Gregory M. , Currie Philip J. , DeBuhr Christopher L. , Kobayashi Yoshitsugu
Published: December 2023

Tyrannosaurids were large carnivorous dinosaurs that underwent major changes in skull robusticity and body proportions as they grew, suggesting that they occupied different ecological niches during their life span. Although adults commonly fed on dinosaurian megaherbivores, the diet of juvenile tyrannosaurids is largely unknown. Here, we describe a remarkable specimen of a juvenileGorgosaurus libratusthat preserves the articulated hindlimbs of two yearling caenagnathid dinosaurs inside its abdominal cavity. The prey were selectively dismembered and consumed in two separate feeding events. This predator-prey association provides direct evidence of an ontogenetic dietary shift in tyrannosaurids. Juvenile individuals may have hunted small and young dinosaurs until they reached a size when, to satisfy energy requirements, they transitioned to feeding on dinosaurian megaherbivores. Tyrannosaurids occupied both mesopredator and apex predator roles during their life span, a factor that may have been key to their evolutionary success.
In vivo protein turnover rates in varying oxygen tensions nominate MYBBP1A as a mediator of the hyperoxia response
Authors: Chen Xuewen , Haribowo Augustinus G. , Baik Alan H. , Fossati Andrea , Stevenson Erica , Chen Yiwen R. , Reyes Nabora S. , Peng Tien , Matthay Michael A. , Traglia Michela , Pico Alexander R. , Jarosz Daniel F. , Buchwalter Abigail , Ghaemmaghami Sina , Swaney Danielle L. , Jain Isha H.
Published: December 2023

Oxygen deprivation and excess are both toxic. Thus, the body’s ability to adapt to varying oxygen tensions is critical for survival. While the hypoxia transcriptional response has been well studied, the post-translational effects of oxygen have been underexplored. In this study, we systematically investigate protein turnover rates in mouse heart, lung, and brain under different inhaled oxygen tensions. We find that the lung proteome is the most responsive to varying oxygen tensions. In particular, several extracellular matrix (ECM) proteins are stabilized in the lung under both hypoxia and hyperoxia. Furthermore, we show that complex 1 of the electron transport chain is destabilized in hyperoxia, in accordance with the exacerbation of associated disease models by hyperoxia and rescue by hypoxia. Moreover, we nominate MYBBP1A as a hyperoxia transcriptional regulator, particularly in the context of rRNA homeostasis. Overall, our study highlights the importance of varying oxygen tensions on protein turnover rates and identifies tissue-specific mediators of oxygen-dependent responses.
Small-molecule targeting AMPA-mediated excitotoxicity has therapeutic effects in mouse models for multiple sclerosis
Authors: Zhai Dongxu , Yan Shuxin , Samsom James , Wang Le , Su Ping , Jiang Anlong , Zhang Haorui , Jia Zhengping , Wallach Izhar , Heifets Abraham , Zanato Chiara , Tseng Chih-Chung , Wong Albert H.C. , Greig Iain R. , Liu Fang
Published: December 2023

While most research and treatments for multiple sclerosis (MS) focus on autoimmune reactions causing demyelination, it is possible that neurodegeneration precedes the autoimmune response. Hence, glutamate receptor antagonists preventing excitotoxicity showed promise in MS animal models, though blocking glutamate signaling prevents critical neuronal functions. This study reports the discovery of a small molecule that prevents AMPA-mediated excitotoxicity by targeting an allosteric binding site. A machine learning approach was used to screen for small molecules targeting the AMPA receptor GluA2 subunit. The lead candidate has potent effects in restoring neurological function and myelination while reducing the immune response in experimental autoimmune encephalitis and cuprizone MS mouse models without affecting basal neurotransmission or learning and memory. These findings facilitate development of a treatment for MS with a different mechanism of action than current immune modulatory drugs and avoids important off-target effects of glutamate receptor antagonists. This class of MS therapeutics could be useful as an alternative or complementary treatment to existing therapies.
Emergence of cefiderocol resistance during ceftazidime/avibactam treatment caused by a large genomic deletion, including
ampD
and
piuCD
genes, in
Pseudomonas aeruginosa
Authors: Gomis-Font María A. , Clari María A. , López-Causapé Carla , Navarro David , Oliver Antonio
Published: December 2023

We report the emergence of cefiderocol resistance during the treatment of a ST312
Pseudomonas aeruginosa
respiratory infection with ceftazidime/avibactam. whole genome sequencing (WGS) revealed that resistance was caused by a large genomic deletion, including PiuDC (iron transport system) and AmpD (
ampC
negative regulator), driven by the integration of phage DNA. Thus, our findings alert that this type of deletion could be an efficient (two mechanisms in one step) specific cefiderocol resistance mechanism that might occur nonspecifically upon treatment with β-lactams that select for AmpC overexpression.
The Human TREX-2 Complex Interacts with Subunits of the ORC Complex
Authors: Kurshakova M. M. , Georgieva S. G. , Kopytova D. V.
Published: December 2023

The TREX-2 protein complex is the key complex involved in the export of mRNA from the nucleus to the cytoplasm through the nuclear pores. Previously, a joint protein complex of TREX-2 with ORC was isolated in D. melanogaster. It was shown that the interaction of TREX-2 with ORC is necessary for efficient mRNA export from the nucleus to the cytoplasm. In this work, we showed that the TREX-2-ORC joint complex is also formed in human cells.
CMV neuroretinitis in a post-transplant patient
Authors: Bonnet Louis Antoine , Evans Kay Frances
Published: December 2023

This report presents an atypical case of neuroretinitis in a post-transplant patient. A man in his 40s presented to a provincial ophthalmology service with unilateral left visual loss. He was immunosuppressed following orthotopic liver transplantation for end-stage liver cirrhosis secondary to primary sclerosing cholangitis. He had received his third Pfizer-BioNTech COVID-19 booster vaccine 34 days prior to symptom onset. His presenting left visual acuity was 6/36. His left optic nerve head was grossly swollen with peripapillary haemorrhage, intraretinal and subretinal fluid extending to involve the fovea. His serological and radiological investigations were all negative except for serum IgG and IgM positivity to cytomegalovirus (CMV). Following the commencement of antiviral treatment and systemic steroids, his neuroretinitis improved with visual recovery to 6/4.5. This report describes an atypical presentation of neuroretinitis in an immunocompromised patient without AIDS but with evidence of CMV exposure.
Characteristics of patients attached to near-retirement family physicians: a population-based serial cross-sectional study in Ontario, Canada
Authors: Premji Kamila , Green Michael E , Glazier Richard H , Khan Shahriar , Schultz Susan E , Mathews Maria , Nastos Steve , Frymire Eliot , Ryan Bridget L
Published: December 2023

Objectives

Population ageing is a global phenomenon. Resultant healthcare workforce shortages are anticipated. To ensure access to comprehensive primary care, which correlates with improved health outcomes, equity and costs, data to inform workforce planning are urgently needed. We examined the medical and social characteristics of patients attached to near-retirement comprehensive primary care physicians over time and explored the early-career and mid-career workforce’s capacity to absorb these patients.

Design

A serial cross-sectional population-based analysis using health administrative data.

Setting

Ontario, Canada, where most comprehensive primary care is delivered by family physicians (FPs) under universal insurance.

Participants

All insured Ontario residents at three time points: 2008 (12 936 360), 2013 (13 447 365) and 2019 (14 388 566) and all Ontario physicians who billed primary care services (2008: 11 566; 2013: 12 693; 2019: 15 054).

Outcome measures

The number, proportion and health and social characteristics of patients attached to near-retirement age comprehensive FPs over time; the number, proportion and characteristics of near-retirement age comprehensive FPs over time. Secondary outcome measures: The characteristics of patients and their early-career and mid-career comprehensive FPs.

Results

Patient attachment to comprehensive FPs increased over time. The overall FP workforce grew, but the proportion practicing comprehensiveness declined (2008: 77.2%, 2019: 70.7%). Over time, an increasing proportion of the comprehensive FP workforce was near retirement age. Correspondingly, an increasing proportion of patients were attached to near-retirement physicians. By 2019, 13.9% of comprehensive FPs were 65 years or older, corresponding to 1 695 126 (14.8%) patients. Mean patient age increased, and all physicians served markedly increasing numbers of medically and socially complex patients.

Conclusions

The primary care sector faces capacity challenges as both patients and physicians age and fewer physicians practice comprehensiveness. Nearly 15% (1.7 million) of Ontarians may lose their comprehensive FP to retirement between 2019 and 2025. To serve a growing, increasingly complex population, innovative solutions are needed.
Association between the neutrophil-to-lymphocyte ratio and psoriasis: a cross-sectional study of the National Health and Nutrition Examination Survey 2011–2014
Authors: Hong Jiaxin , Lian Ni , Li Min
Published: December 2023

Objectives

To investigate the association between the neutrophil-to-lymphocyte ratio (NLR) and psoriasis.

Design

Cross-sectional study.

Setting

National Health and Nutrition Examination Survey 2011–2014.

Participants

A subsample of 8387 individuals aged 18 years and older were screened for inclusion, of whom 238 reported a diagnosis of psoriasis.

Primary and secondary outcome measures

Psoriasis and the severity of psoriasis were defined according to participants’ self-reports. Weighted logistic regression, subgroup and restricted cubic spline (RCS) analyses were conducted to estimate the potential relationship of the NLR with psoriasis.

Results

In the fully adjusted models, the fourth quartile of the NLR was significantly and positively associated with the presence of psoriasis using the first quartile as a reference (OR: 2.22, 95% CI: 1.27 to 3.87, p=0.01). Elevated NLR was associated with an increased odds of having more severe psoriasis for the highest quartile (vs the lowest quartile), with an OR of 2.43 (95% CI: 1.10 to 5.36, p=0.003). The association between the NLR and psoriasis differed across prespecified subgroups by age, sex, race, income and education. A non-linear correlation of the NLR with psoriasis was observed using univariable and multivariable RCS (all p for non-linearity <0.05).

Conclusions

The NLR was non-linearly and positively correlated with the presence of psoriasis, and our findings suggest a significant association between the NLR and the severity of psoriasis. The potential role and value in the clinical diagnosis and prognostic assessment of the NLR in psoriasis calls for further longitudinal studies.
Digital health coaching to improve patient preparedness for elective lower limb arthroplasty: a quality improvement project
Authors: Powley Nicola , Tew Garry A , Durrand James , Carr Esther , Nesbitt Alexander , Hackett Rhiannon , Gray Joanne , McCarthy Stephen , Beatty Matthew , Huddleston Robbie , Danjoux Gerard
Published: December 2023

Major surgery carries high risks with comorbidities, frailty and health risk behaviours meaning patients are often unprepared for the physiological insult. Since 2018, the Prepwell programme at South Tees Hospitals NHS Foundation Trust has supported patients to improve their preoperative health and fitness. In April 2020, the face-to-face service was suspended due to the pandemic, leading to the team implementing a three-tiered remote digital support pathway, including digital health coaching via a mobile phone application.

Methods

Patients scheduled for elective lower limb arthroplasty were offered 8 weeks of digital health coaching preoperatively. Following consent, participants were assigned a personal health coach to set individual behaviour change goals supported by online resources, alongside a digitally delivered exercise programme. Participants completed self-assessment questionnaires at Entry to, and Exit from, the programme, with outcome data collected 21 days postoperatively. The primary outcome was the change in Patient Activation Measure (PAM).

Results

Fifty-seven of 189 patients (30.2%) consented to referral for digital health coaching. Forty participants completed the 8-week programme. Median PAM increased from 58.1 to 67.8 (p=0.002). Thirty-five per cent of participants were in a non-activated PAM level at Entry, reducing to 15% at Exit with no participants in PAM level 1 at completion. Seventy-one percent of non-activated participants improved their PAM by one level or more, compared with 45% for the whole cohort. Median LOS was 2 days, 1 day less than the Trust’s arthroplasty patient population during the study period (unadjusted comparison).

Conclusions

Digital health coaching was successfully implemented for patients awaiting elective lower limb arthroplasty. We observed significant improvements in participants’ PAM scores after the programme, with the largest increase in participants with lower activation scores at Entry. Further study is needed to confirm the effects of digital health coaching in this and other perioperative groups.
Health insurance coverage and access to maternal healthcare services by women of reproductive age in Nigeria: a cross-sectional study
Authors: Esan Oluwaseun Taiwo , Adeomi Adeleye Abiodun , Afolabi Olusegun Temitope
Published: December 2023

Background

Inequitable financial access to maternal healthcare services (MHS) has contributed to maternal deaths, especially in low and middle-income countries. Evidence in the literature on women’s health insurance status and access to MHS in Nigeria is sparse. This study aimed to determine the association between health insurance coverage and access to MHS among Nigerian women of reproductive age.

Methods

This is a cross-sectional study that used the 2018 Nigeria Demographic and Health Survey (NDHS). A total of 12 935 women who had their last delivery within 2 years before the NDHS were included in the study. Access to MHS was assessed by using the number of antenatal care (ANC) visits and health facility delivery. Adjusted logistic regression models were fit to control for individual, household and community-level factors.

Results

Only 18.5% and 40.6% of the women in the study attended ≥8 ANC visits and delivered in a health facility, respectively. About 39.5% of women who had ≥8 ANC visits and 71.8% of those who delivered in health facilities had health insurance coverage. There were statistically significant associations between having health insurance and attendance of ≥8 ANC visits (adjusted OR (AOR) 1.9; 95% CI 1.26–2.95) and women delivering at a health facility (AOR 2.0; 95% CI 1.39–2.82). There were also lower significant odds of accessing ≥8 ANC visits and delivering in health facilities among the rural dwellers, unemployed, those with lower educational status and those in the lower social economic quintiles.

Conclusion

There was a low uptake of health insurance programmes among the Nigerian women in this study. Having health insurance coverage was significantly associated with ≥8 ANC visits and women delivering in health facilities. Thus, providing health insurance may be an important way to improve women’s access to MHS in Nigeria.
Taiwan solar-powered UAV flight endurance record
Authors: Hong Ting-Kai , Lin Chung-Yan , Lin Huan-Jung , Ruseno Neno
Published: December 2023

Solar-powered unmanned aerial vehicles (UAVs) possess a unique capability to maintain continuous flight for hours, days, weeks, or even months. This research aims to develop a solar-powered UAV that can fly at low altitudes with extended endurance to establish a new record for full-day continuous flight in Taiwan. The UAV was designed with a 4.7 m wingspan and a T-tail configuration to achieve this goal, utilizing materials and components available in the current market. The flight test was conducted on 2 June 2022, resulting in a remarkable 21 h and 50 min of flight endurance, setting a record in Taiwan. While the full-day flight endurance target was not met, the UAV demonstrates the potential to achieve greater endurance with improvements in its construction and operational aspects.
Quark/gluon discrimination and top tagging with dual attention transformer
Authors: He Minxuan , Wang Daohan
Published: December 2023

Jet tagging is a crucial classification task in high energy physics. Recently the performance of jet tagging has been significantly improved by the application of deep learning techniques. In this study, we introduce a new architecture for jet tagging: the particle dual attention transformer (P-DAT). This novel transformer architecture stands out by concurrently capturing both global and local information, while maintaining computational efficiency. Regarding the self attention mechanism, we have extended the established attention mechanism between particles to encompass the attention mechanism between particle features. The particle attention module computes particle level interactions across all the particles, while the channel attention module computes attention scores between particle features, which naturally captures jet level interactions by taking all particles into account. These two kinds of attention mechanisms can complement each other. Further, we incorporate both the pairwise particle interactions and the pairwise jet feature interactions in the attention mechanism. We demonstrate the effectiveness of the P-DAT architecture in classic top tagging and quark–gluon discrimination tasks, achieving competitive performance compared to other benchmark strategies.
Testable likelihoods for beyond-the-standard model fits
Authors: Beck Anja , Reboud Méril , van Dyk Danny
Published: December 2023

Studying potential BSM effects at the precision frontier requires accurate transfer of information from low-energy measurements to high-energy BSM models. We propose to use normalising flows to construct likelihood functions that achieve this transfer. Likelihood functions constructed in this way provide the means to generate additional samples and admit a “trivial” goodness-of-fit test in form of a$$\chi ^2$$χ2test statistic. Here, we study a particular form of normalising flow, apply it to a multi-modal and non-Gaussian example, and quantify the accuracy of the likelihood function and its test statistic.
Composition and Diversity of Bird Community in the Chemoga Wetland and the Associated Human-Modified Landscapes, East Gojjam, Ethiopia
Authors: Gibru Amare , Hunduma Tadesse , Biru Yihew , Fekensa Tesfu
Published: December 2023

Wetlands and their surrounding habitats are rich in avian communities. However, the desire for human needs has degraded these ecosystems. The current study was carried out in the Chemoga wetland and its associated human-modified landscapes in East Gojjam, Ethiopia, during both the dry and wet seasons from December 2020 to August 2021. The study aims to investigate the species composition and diversity of the bird community. A line transect sampling technique was used in the human-modified landscapes, whereas the total counting method was used to study the wetland habitat. PAST software and Microsoft Excel were used for data analysis. Using a paired diversity T-test, the effect of seasons and habitats on species richness and abundance was compared. In total, 3890 individuals, 76 species, 31 families, and 13 orders were recorded from the studied habitats. Our results showed that the Chemoga wetland with low human disturbance had a greater number of birds and abundance than the human-modified habitats at

P

 < 0.05. Moreover, in both wet and dry seasons, the Chemoga wetland (

P

 < 0.05) shows significant difference in the abundance of avian species. But, in the human-modified habitat, there is no significant difference in the abundance of avian species (

P

 > 0.05). The majority of birds scored frequent and common on the ordinal scale in both habitats and seasons. This study confirms that the studied habitats are important for the conservation of birds. Conservation measures are thus required to limit disturbances and foster species survival in the area.
Length-Weight Relationships (LWRs) of Four Loach Species of the Cobitidae Family from the Surma River, Bangladesh
Authors: Nasren Shamima , Rahman MD Zobayer , Islam MD Shahinul , Mia Rasel , Mian Sohel , Mamun Md. Abdullah-Al
Published: December 2023

Four loaches, namely, Lepidocephalichthys guntea (Hamilton, 1822), Lepidocephalichthys annandalei (Chaudhuri, 1912), Lepidocephalichthys thermalis (Valenciennes, 1846), and Lepidocephalichthys berdmorei (Blyth, 1860) from the Cobitidae family, were collected from the Surma River, Bangladesh. Of the total 376 speciminia, 193 males (51.32%) and 183 females (48.67%) in number; were collected with the support of local fishermen using a variety of nets at 15-day intervals from November 2022 to April 2023. The length-weight relationship (LWR) parameters were analyzed using the equation

W
=
a

L

b

. L. annandalei displayed a notable isometric growth pattern, with a condition factor (K) ranging from 0.725 to 0.734. In addition, L. thermalis exhibited isometric growth among males, while females showcased positive allometric growth with a condition factor (K) varying between 0.697 and 0.714. L. guntea exhibited a consistent positive allometric growth pattern across all aspects, with a condition factor (K) ranging from 0.729 to 0.738. In contrast, L. berdmorei demonstrated positive allometric growth, but males and females both exhibited a negative allometric growth pattern. The condition factor (K) for L. berdmorei ranged from 0.699 to 0.702. This suggests a complex growth pattern influenced by both length and weight in every experimental loach. The research underscores the importance of recognizing gender-specific variations in growth patterns within species.
The Prevalence and Determinants of Inappropriate Oral Anticoagulant Use in Patients with Atrial Fibrillation, in Resource‐Limited Setting
Authors: Yabeyu Abdella Birhan , Mohammed Samiya Yassin , Legesse Eshetu Shiferaw , Adugna Meaza , Kifle Zemene Demelash
Published: December 2023

Introduction. Anticoagulation treatment is routinely underused in patients with atrial fibrillation (AF), particularly in settings with limited resources. The current study is aimed at evaluating the appropriateness of oral anticoagulation treatment among AF patients at the Yekatit 12 Hospital Medical College (Y12HMC), Addis Ababa, Ethiopia. Methods. Institutional‐based retrospective cross‐sectional study conducted in Y12HMC from November 2019 to March 2020. During the study period, 256 patients’ medical records were found; 231 of them met the eligibility criteria and were included in the study. The data were analyzed using SPSS version 25, descriptive statistics were used to summarize the data, and binary logistic regression was performed to identify predictors of inappropriate anticoagulation management. Results. The majority of study participants were males (55.8%), and over half of them (57.6%) had a nonvalvular type of AF. The majority of patients (61.9%) were receiving anticoagulant treatment, and of them, warfarin was prescribed to most of the study subjects (71.3%). Nearly half (47.6%) of the study participants had inappropriate anticoagulation treatment; among these, the majority of them (69.1%) were from a valvular type of AF. Patients with a valvular type of AF and having the diagnosis of congestive heart disease as comorbidity showed a statistically significant association towards inappropriate anticoagulation management. Conclusion. According to the study, a significant portion of AF patients received inappropriate anticoagulant treatment, which may play a significant role for the increased risk of stroke in these groups of patients. All of the inappropriate cases were due to failure to start anticoagulant treatment.
Vertical Marginal Discrepancy of a Monolithic Zirconia Crown with Different Cement Spaces
Authors: Alkhallagi Turki , Alzahrani Meshari , Alkathiri Majed Ali , Basunbul Ghadeer I. , Marghalani Amin
Published: December 2023

The long-term clinical success of indirect restorations highly depends on their marginal integrity. The cement space is an element that might affect the marginal integrity, but it can be altered during the configuring of the computer-assisted designing/computer-aided manufacturing (CAD–CAM) restoration. However, there is controversy in the literature regarding the effect of the cement space on the precision of zirconia crown marginal adaptation. The aim of this study was to measure the vertical marginal discrepancies between different cement thickness settings for CAD–CAM monolithic zirconia restorations. Material and Methods. An artificial mandibular right molar tooth mounted on a typodont was prepared for a zirconia crown using the standard method. The study sample consisted of 30 zirconia crowns (Zenostar Zr Translucent Zirconia, Weiland Dental, Germany) milled using an (iMes-iCore) milling machine. Each group of 10 crowns was designed with 30–50 and 70 μm spacer thicknesses. The vertical marginal adaptation at the center of the four different planes (mesial, distal, buccal, and palatal) was measured under a microscope at 40x magnification. A one-way analysis of variance test was used for statistical analysis. Results. The mean of Group 30 was 27.45; of Group 50 was 22.22; and of Group 70 was 22.90. There was no statistically significant difference between the groups (

p
≥
0.5

). Conclusions. The increase in the cement space up to 70 μm did not influence the vertical marginal adaptation of the monolithic zirconia crowns.
Figure S12 from Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors
Authors: Juarez Dennis , Buono Roberta , Matulis Shannon M. , Gupta Vikas A. , Duong Madeleine , Yudiono Jacob , Paul Madhuri , Mallya Sharmila , Diep Grace , Hsin Peter , Lu Alexander , Suh Sang Mi , Dong Vy M. , Roberts Andrew W. , Leverson Joel D. , Jalaluddin Muhammad , Liu Zhuangzhuang , Bueno Orlando F. , Boise Lawrence H. , Fruman David A.
Published: December 2023

Supplementary Figure 12 contains additional data on the role of PERK in statin-induced ISR in MM cell lines.
Gastric Glomus Tumors: The Roles of Endoscopic Ultrasound and Shared Decision-Making
Authors: Malik Alexander , Yousaf Muhammad Nadeem , Samiullah Sami , Tahan Veysel
Published: December 2023

Gastric glomus tumors (GGTs) are mesenchymal neoplasms with indolent behavior that originate from the subepithelial layers of the stomach and represent up to 1% of all gastric tumors. GGT is detected incidentally during esophagogastroduodenoscopy (EGD) in a proportion of patients. Endoscopic ultrasound (EUS) evaluation of GGT is essential to establish the diagnosis and to differentiate it from gastrointestinal stromal tumors or gastric neuroendocrine tumors. An 80-year-old man who presented for abdominal discomfort was incidentally found to have a gastric antral nodule on EGD. Endoscopic biopsy demonstrated moderately erythematous gastric antral mucosa and a 1.5 cm subepithelial lesion along the greater curvature. An EUS revealed a subepithelial 1.6 cm × 1.3 cm isoechoic, homogenous lesion with small calcifications. Immunohistochemical staining of the fine needle biopsy specimen of the nodule was positive for neoplastic cells, smooth muscle actin, vimentin, patchy muscle-specific actin, and synaptophysin. There were no atypical cytologic features. These findings were consistent with GGT. The patient was not deemed to be a candidate for surgical resection due to advanced age and resolution of his symptoms. A shared decision was made to pursue regular surveillance. EUS is essential for evaluation of GGT. Currently, there are no guideline recommendations for surveillance of GGT detected on routine EGD in asymptomatic individuals. A definitive surgical treatment with partial gastrectomy was favored in previously published literature. For asymptomatic patients with GGT or those with resolution of symptoms, careful surveillance with serial abdominal imaging and EUS may be a reasonable option, especially in older patients with poor surgical candidacy.
EVALUATION OF METHODS FOR TOTAL RNA EXTRACTION FROM THE ENDOSPERM OF COCOS NUCIFERA VAR. MAKAPUNO IN VIETNAM FOR MOLECULAR ANALYSIS
Authors: Nguyen Thanh-Diem , Vu Huyen-Trang
Published: December 2023

Sap coconut (Cocos nucifera L. var. makapuno) in Vietnam is a mutant coconut variant; coconut water is in the state of lotus glue, and coconut rice is like cream. For high-quality transcriptome, sequencing, quality, purity and concentration of RNA are the key factors. However, coconut endosperm tissue has higher stiffness and fatness than the leaf tissue, which complicates the extraction process. Moreover, RNA is much more difficult to preserve than DNA. In this study, various RNA extraction methods were examined in Vietnamese waxy coconut endosperm tissue samples. Optimum extraction and preservation of the RNA using the simplest possible chemicals was the objective of this study. The modified CTAB method with LiCl and the TRI reagent method were tested and evaluated. The purity, concentration and quality of RNA after storage were improved. The findings indicated that the TRIsure extraction method with the addition of NaCl and β-mercaptoethanol yielded optimum RNA quality. The RNA concentration was 159 ng/µL, with a purity ratio of 1.94 ± 0.04 for A260/A280 and 1.58 ± 0.02 for A260/230. RNA samples remained stable for up to 3 weeks when stored in absolute ethanol at 8°C–10°C, which significantly reduced their degradation during transportation. This study facilitated the use of simple chemicals for high-quality RNA extraction from coconut endosperm and its preservation for applications in high throughput sequencing.
Homeopathic Repertory of Modern Drugs. 2.ed.
Authors:   Universidade de São Paulo. Faculdade de Medicina, Teixeira Marcus Zulian
Published: December 2023

Following the pattern of traditional homeopathy, this work proposes to employ modern drugs according to the principle of therapeutic similitude, stimulating the healing rebound effect (vital reaction) of the organism through the administration of substances (in infinitesimal doses) that caused similar symptoms in healthy human. Is worth emphasizing that the pathogenetic effects (primary actions) of classical homeopathic medicines correspond to the therapeutic, adverse and side effects of conventional drugs, which should be similar to totality of the symptoms of the patient to stimulate the curative vital reaction (curative rebound effect) according to the principle of therapeutic similitude. To make this proposal operative, a Homeopathic Materia Medica of Modern Drugs was elaborated, where the therapeutic, adverse and side effects of drugs were grouped following the structure of the traditional homeopathic materia medica, while giving particular value to the frequency of the symptoms observed during the phases of study of the drugs. In order to facilitate the selection of the individualized remedy (i.e., similar to the totality of symptoms of the patient), and thus the clinical application of the present proposal, at a later stage it was also elaborated a Homeopathic Repertory of Modern Drugs, where symptoms and remedies are arranged as in the traditional homeopathic repertories, described in this work. This book is the third volume of the New homeopathic medicines: use of modern drugs according to the principle of similitude collection.
Short‐Term Mortality Among Pediatric Patients With Heart Diseases Undergoing Veno‐Arterial Extracorporeal Membrane Oxygenation: A Systematic Review and Meta‐Analysis
Authors: Zhou Jingjing , Wang Haiming , Zhao Yunzhang , Shao Junjie , Jiang Min , Yue Shuai , Lin Lejian , Wang Lin , Xu Qiang , Guo Xinhong , Li Xin , Liu Zifan , Chen Yundai , Zhang Ran
Published: December 2023

Background

Veno‐arterial extracorporeal membrane oxygenation serves as a crucial mechanical circulatory support for pediatric patients with severe heart diseases, but the mortality rate remains high. The objective of this study was to assess the short‐term mortality in these patients.

Methods and Results

We systematically searched PubMed, Embase, and Cochrane Library for observational studies that evaluated the short‐term mortality of pediatric patients undergoing veno‐arterial extracorporeal membrane oxygenation. To estimate short‐term mortality, we used random‐effects meta‐analysis. Furthermore, we conducted meta‐regression and binomial regression analyses to investigate the risk factors associated with the outcome of interest. We systematically reviewed 28 eligible references encompassing a total of 1736 patients. The pooled analysis demonstrated a short‐term mortality (defined as in‐hospital or 30‐day mortality) of 45.6% (95% CI, 38.7%–52.4%). We found a significant difference (
P
<0.001) in mortality rates between acute fulminant myocarditis and congenital heart disease, with acute fulminant myocarditis exhibiting a lower mortality rate. Our findings revealed a negative correlation between older age and weight and short‐term mortality in patients undergoing veno‐arterial extracorporeal membrane oxygenation. Male sex, bleeding, renal damage, and central cannulation were associated with an increased risk of short‐term mortality.

Conclusions

The short‐term mortality among pediatric patients undergoing veno‐arterial extracorporeal membrane oxygenation for severe heart diseases was 45.6%. Patients with acute fulminant myocarditis exhibited more favorable survival rates compared with those with congenital heart disease. Several risk factors, including male sex, bleeding, renal damage, and central cannulation contributed to an increased risk of short‐term mortality. Conversely, older age and greater weight appeared to be protective factors.
Ischemic Stroke Temporally Associated With New-Onset Atrial Fibrillation: A Population-Based Registry-Linkage Study
Authors: Putaala Jukka , Teppo Konsta , Halminen Olli , Haukka Jari , Tiili Paula , Jaakkola Jussi , Karlsson Elin , Linna Miika , Mustonen Pirjo , Kinnunen Janne , Kiviniemi Tuomas , Aro Aapo , Hartikainen Juha , Airaksinen Juhani K.E. , Lehto Mika ,   on behalf of the FinACAF Study Group
Published: December 2023

BACKGROUND:

Limited data exist on the temporal relationship between new-onset atrial fibrillation (AF) and ischemic stroke and its impact on patients’ clinical characteristics and mortality.

METHODS:

A population-based registry-linkage database includes all patients with new-onset AF in Finland from 2007 to 2018. Ischemic stroke temporally associated with AF (ISTAF) was defined as an ischemic stroke occurring within ±30 days from the first AF diagnosis. Clinical factors associated with ISTAF were studied with logistic regression and 90-day survival with Cox proportional hazards analysis.

RESULTS:

Among 229 565 patients with new-onset AF (mean age, 72.7 years; 50% female), 204 774 (89.2%) experienced no ischemic stroke, 12 209 (5.3%) had past ischemic stroke >30 days before AF, and 12 582 (5.8%) had ISTAF. The annual proportion of ISTAF among patients with AF decreased from 6.0% to 4.8% from 2007 to 2018. Factors associated positively with ISTAF were higher age, lower education level, and alcohol use disorder, whereas vascular disease, heart failure, chronic kidney disease cancer, and psychiatric disorders were less probable with ISTAF. Compared with patients without ischemic stroke and those with past ischemic stroke, ISTAF was associated with ≈3-fold and 1.5-fold risks of death (adjusted hazard ratios, 2.90 [95% CI, 2.76–3.04] and 1.47 [95% CI, 1.39–1.57], respectively). The 90-day survival probability of patients with ISTAF increased from 0.79 (95% CI, 0.76–0.81) in 2007 to 0.89 (95% CI, 0.87–0.91) in 2018.

CONCLUSIONS:

ISTAF depicts the prominent temporal clustering of ischemic strokes surrounding AF diagnosis. Despite having fewer comorbidities, patients with ISTAF had worse, albeit improving, survival than patients with a history of or no ischemic stroke.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04645537. URL:
https://www.encepp.eu
; Unique identifier: EUPAS29845.
Inflation and Attention Thresholds
Authors: Korenok Oleg , Munro David , Chen Jiayi
Published: December 2023

One of the dangers of high inflation is that it can cause individuals to pay close attention to it. This internalization of inflation can lead to an accelerationist regime, making inflation harder to control. We empirically assess the relationship between attention and inflation for 38 countries. Our measures of attention are constructed from internet search behavior or the popularity of inflation mentions on Twitter. We find evidence that attention thresholds exist for most of the countries and that they typically occur between 2-4% inflation. We also document interesting variability across countries and find similar thresholds in newspaper coverage of inflation.
Care of People with Special Needs between the Prophetic Tradition and Algerian Law: The National Association al-Ṣāber Yanāl for People with Special Needs as a Model
Authors: Djouahi Abdelhafid , Ramchahi Abdollatif Ahmadi , Suliaman Ishak
Published: December 2023

This study entitled: “Care for people with special needs between the Sunnah of the Prophet and the Algerian law: (The National Association al-Saber Yanal for people with special needs as a model)” discussed the definitions related to people with special needs in linguistic, Qurʾānic and Sunnah context, as well as their definition in Algerian law, while dealing with the most important provisions of the constitution about their rights according to the law 02–09. This study sheds light on their rights in the Sunnah of the Prophet P.B.U.H and had a comprehensive discussion on the difference in their right between the Sunnah of the Prophet P.B.U.H and the Algerian law. The study has also done a field study on al-Ṣāber Yanāl Association for people with special needs in Ouargla (Algeria). The researchers used the inductive approach by extrapolating the hadiths of the Prophet P.B.U.H about people with special needs, and the comparative analytical approach to discuss and analyze the information obtained, and to compare the rights of people with special needs in Algerian law with their rights in the Sunnah of the Prophet P.B.U.H, and the applied approach, which included a field study on al-Ṣāber Yanāl Association, conducted an interview with four (4) members of the permanent members of the association. The study found that the Algerian law is considered a statutory law that falls short of containing the problems and issues of people of special needs, while the Sunnah of the Prophet P.B.U.H was totally the opposite; this is because the law that was legislated was deficient in several aspects and was not studied by qualified officials, and that the good aspects is bad implemented, in contrast to the many rights granted to them by the Prophet’s Sunnah, the most important of which is integrating them into society and making them part of it.
Transition Milestones, Psychological Distress, and Suicidal Ideation Among Transgender Adults: A Structural Equation Analysis
Authors: Klein Hugh , Washington Thomas A.
Published: December 2023

Purpose: This paper examines the relationships among transition milestones (i.e., transition-related events in transgender persons’ lives that demarcate their life circumstances before vs. afte a milestone was reached), psychological distress, and suicidal ideation in a large sample of transgender adults. Methods: Data from the 2015 U.S. National Transgender Survey were used to examine 11 specific transition milestones in a sample of 27,715 transgender Americans aged 18 or older. The Kessler-6 scale was used to measure psychological distress and a dichotomous measure of suicidal ideation during the past year was the other main outcome measure. Covariates in the multivariate analysis included demographic measures, variables assessing support and discrimination, and 11 transition milestones. Results: Bivariate analyses revealed that, in almost all instances, reaching specific transition milestones led to reduced psychological distress and diminished odds of suicidal ideation. Multivariate analysis revealed that psychological distress was a strong predictor of suicidal ideation, but transition milestones were not retained in the final model. Structural equation analysis showed that three specific transition milestones (namely, changing one’s name and/or gender on legal documents, taking gender-affirming hormones, having had any gender-conforming surgical procedures) influenced suicidal ideation indirectly, through their direct impact on psychological distress. Conclusions: Reaching specific transition milestones plays an important role in many transgender adults’ lives, and may be highly beneficial in helping them to reduce psychological distress. This, in turn, is likely to have a positive impact upon their likelihood of contemplating suicide.