bluuebunny/crossref_metadata_2025 huggingface dataset:
Transitional care for older adults with chronic illness: A qualitative inquiry
Authors: Isac Chandrani , Lee Premila
Published: January 2024

Background

Improved public health strategies and medical advancements have expanded older adults' survival after acute insults from chronic diseases. The resultant increase in disability and care requirements among older adults is significant. However, transitional care interventions to support the efficient transition from acute care settings to home are primitive in developing countries like India.

Objective

This qualitative survey aimed to estimate the transitional care requirements of older adults with chronic illness discharged from acute care facilities.

Methods

Descriptive phenomenological approach was utilised for this qualitative study. The older adult‐family caregiver dyads fulfilling the inclusion criteria were interviewed until the achievement of information saturation. The transcribed narratives between the researcher, older adults and their caregivers were thematically analysed. Consolidated Criteria for Reporting Qualitative Research (COREQ) served as the framework for reporting this research.

Results

Thirteen older adult‐caregiver dyads participated in the semi‐structured interview, which yielded six themes. Older adults have a hidden self with characteristics ranging between a continuum of ‘insistence’ to ‘giving up’. Caregiver attributes identified from this inquiry were exhaustion, engagement and empowerment. The remaining four themes which constitute the framework for the ‘transitional care progression’ model include ‘complications are mature when identified among older adults’, ‘medication knowledge is proportionate with its compliance’, ‘ignorance of supportive care increases caregiver burden’ and ‘deficient follow‐up practices compromise health’.

Conclusions

Transitional care for older adults with chronic illness is premature in developing countries. However, the needs of older adults with chronic disease and their caregivers evolved from the present study align with global perspectives. Themes generated from the current qualitative interview, blended with evidence‐based interventions, yielded the transitional care progression model, which serves as the only available framework for implementing transitional care in the region.

Implications for Practice

Future research to establish the feasibility and validity of the ‘transitional care progression model’ is forecasted. The model requires inclusion within the healthcare curriculum. Professional nurses prepared to implement coordinated transitional care pathways are recommended.
Orthokeratology effect on the corneoscleral profile: Beyond the bull's eye
Authors: Martínez‐Plaza Elena , López‐de la Rosa Alberto , Molina‐Martín Ainhoa , Piñero David P.
Published: January 2024

Purpose

To assess the impact of 3 months of orthokeratology (ortho‐k) contact lenses (CLs) for myopia correction on the corneoscleral profile, as changes in scleral geometry could serve as indirect evidence of alteration in the corneal biomechanical properties.

Methods

Twenty subjects (40 eyes) were recruited to wear ortho‐k lenses overnight; however, after discontinuation (two CL fractures, one under‐correction and two non‐serious adverse events), 16 subjects (31 eyes) finished a 3‐month follow‐up. Corneoscleral topographies were acquired using the Eye Surface Profiler (ESP) system before and after 3 months of lens wear. Steep (SimKs) and flat (SimKf) simulated keratometry and scleral sagittal height measurements for 13‐, 14‐ and 15‐mm chord lengths were automatically calculated by the ESP software. Additionally, sagittal height and slope were calculated in polar format from 21 radii (0–10 mm from the corneal apex) at 12 angles (0–330°). Linear mixed models were fitted to determine the differences between visits.

Results

SimKs and SimKf were increased significantly (p ≤ 0.02). The sagittal height in polar format increased significantly (p = 0.046) at a radius of 2.5 mm for 150°, 180°, 210° and 240° orientations and at a radius of 3.0 mm for 210°. Additionally, the slope in polar format significantly decreased (p ≤ 0.04) at radii ranges of 0.0–0.5, 0.5–1.0 and 1.0–1.5 mm for multiple angles and at a radii range of 5.0–5.5 mm for 90°. It also increased significantly (p ≤ 0.045) at a radii range of 1.5–2.0 mm for 30° and at radii ranges of 2.0–2.5, 2.5–3.0 and 3.0–3.5 mm for multiple angles. No significant changes were found for any parameter measured from the scleral area.

Conclusions

Three months of overnight ortho‐k lens wear changed the central and mid‐peripheral corneal geometry as expected, maintaining the peripheral cornea and the surrounding sclera stability.
Fatty Infiltration of Multifidus Muscles: An Easily Overlooked Risk Factor for the Severity of Osteoporotic Vertebral Fractures
Authors: Xu Wuyan , Liu Xiaowen , Wu Li , Liang Shaohua , Zhang Ye , Huang Junbing , Zeng Xuwen , Li Siming , Xu Fan , Xiong Yuchao
Published: January 2024

Objectives

Osteoporotic vertebral fractures (OVFs) are a critical public health concern requiring urgent attention, and severe OVFs impose substantial health and economic burdens on patients and society. Analysis of the risk factors for severe OVF is imperative to actively prevent the occurrence of this degenerative disorder. This study aimed to investigate the risk factors associated with the severity of OVF, with a specific focus on changes in the paraspinal muscles.

Methods

A total of 281 patients with a first‐time single‐level acute OVF between January 2016 and January 2023 were enrolled in the study. Clinical and radiological data were collected and analyzed. The cross‐sectional area (CSA) and degree of fatty infiltration (FI) of the paraspinal muscles, including the multifidus muscles (MFMs), erector spinae muscles (ESMs), and psoas major muscles (PSMs), were measured by magnetic resonance imaging (MRI) of the L4/5 intervertebral discs. According to the classification system of osteoporotic fractures (OF classification) and recommended treatment plan, OVFs were divided into a low‐grade OF group and a high‐grade OF group. Univariate and multivariate logistic regression analyse s were performed to identify risk factors associated with the severity of OVF.

Results

Ninety‐eight patients were included in the low‐grade OF group, and 183 patients were included in the high‐grade OF group. Univariate analysis revealed a significantly higher incidence of a high degree of FI of MFMs (OR = 1.71, p = 0.002) and ESMs (OR = 1.56, p = 0.021) in the high‐grade OF group. Further multivariate logistic regression analysis demonstrated that a high degree of FI of the MFMs (OR = 1.71, p = 0.002) is an independent risk factor for the severity of OVF.

Conclusion

A high degree of FI of the MFMs was identified as an independent risk factor for the severity of OVF. Decreasing the degree of FI in the MFMs might lower the incidence of the severity of OVF, potentially reducing the necessity for surgical intervention in OVF patients.
Incomplete Kawasaki disease presenting with a cellulitis‐like plaque: Lessons from an unusual presentation
Authors: Banbury Sara , Gebre Kirubel , Milgraum David M. , Do Ngan , Yan Albert C.
Published: January 2024

Kawasaki disease (KD) is an acute small to medium‐vessel vasculitis that primarily affects children under the age of 5 years. The cause of KD is unknown, but it is hypothesized to be a systemic inflammatory illness triggered by infections in genetically predisposed individuals. Diagnosis of incomplete KD is made in patients with prolonged fever without a source who do not meet diagnostic criteria but have some findings consistent with KD such as elevated inflammatory markers, transaminitis, and echocardiographic findings. We present a 7‐year‐old boy who developed 10 days of fevers and rash that began 3 days after his first dose of hepatitis A vaccination and had notable features of a peculiar cellulitis‐like plaque and peripheral eosinophilia.
Erianin inhibits tumor growth by promoting ferroptosis and inhibiting invasion in hepatocellular carcinoma through the JAK2/STAT3/SLC7A11 pathway
Authors: Chen Liyan , Sun Rongrong , Fang Kun
Published: January 2024

Iron has been found to be involved in the tumor cell proliferation process, which can lead to the increased sensitivity of cancer cells to ferroptosis. Since erianin is associated with oxidative stress in hepatocellular carcinoma (HCC), we hypothesized that the therapeutic effect and mechanism of erianin on HCC is related to ferroptosis. HCC cells were stimulated with increase of erianin concentrations for 24 h, and the survival rates of Huh‐7 and HepG2 cells gradually decreased. After intervention with different doses of erianin, cell proliferation, clone number, and invasion were prominently decreased, apoptosis ratio was increased. Moreover, Nec‐1, CQ, and Z‐VAD had no effect on the cell viability induced by erianin, while the combination of ferroptosis inhibitors (deferoxamine mesylate, ferrostatin‐1, and liproxstatin‐1) and erianin prominently increased cell survival rate. Erianin pretreatment induced ferroptosis by enhancing reactive oxygen species, MDA, and Fe2+ levels, and reducing GSH levels. Erianin activated JAK2/STAT3 pathway and inhibited SLC7A11 and GPX4 expression, thereby inducing ferroptosis. Besides, tumor growth was significantly inhibited in the erianin‐treated mice, and there was no obvious toxicity in the mice. Erianin reduced proliferation and invasion of HCC cells by inducing ferroptosis by blocking the JAK2/STAT3/SLC7A11 pathway, thereby impeding tumor growth.
Awareness of errors is reduced by sleep loss
Authors: Boardman Johanna M. , Cross Zachariah R. , Bravo Michelle M. , Andrillon Thomas , Aidman Eugene , Anderson Clare , Drummond Sean P. A.
Published: January 2024

The ability to detect and subsequently correct errors is important in preventing the detrimental consequences of sleep loss. The Error Related Negativity (ERN), and the error positivity (Pe) are established neural correlates of error processing. Previous work has shown sleep loss reduces ERN and Pe, indicating sleep loss impairs error‐monitoring processes. However, no previous work has examined behavioral error awareness, in conjunction with EEG measures, under sleep loss conditions, and studies of sleep restriction are lacking. Using combined behavioral and EEG measures, we report two studies investigating the impact of total sleep deprivation (TSD) and sleep restriction (SR) on error awareness. Fourteen healthy participants completed the Error Awareness Task under conditions of TSD and 27 completed the same task under conditions of SR. It was found that TSD did not influence behavioral error awareness or ERN or Pe amplitude, however, SR reduced behavioral error awareness, increased the time taken to detect errors, and reduced Pe amplitude. Findings indicate individuals who are chronically sleep restricted are at risk for reduced recognition of errors. Reduced error awareness may be one factor contributing to the increased accidents and injuries seen in contexts where sleep loss is prevalent.
Exploring MicroRNA biogenesis, applications and bioinformatics analysis in livestock: A comprehensive review
Authors: Jaglan Komal , Dhaka S. S. , Magotra Ankit , Patil C. S. , Ghanghas Amandeep
Published: January 2024

Small non‐coding RNAs called microRNAs (miRNAs) control the expression of genes post‐transcriptionally. Their correlation with commercial economic traits including milk, meat and egg production, as well as their effective role in animal productivity, fertility, embryo survival and disease resistance, make them significant in livestock research. The miRNAs exhibit distinct spatial and temporal expression patterns, offering insights into their functional roles within cells and tissues. Aberrant miRNA production can disrupt vital cellular processes and genetic networks, contributing to conditions like metabolic disorders and viral diseases. These short RNA molecules are present in extracellular fluids, displaying remarkable stability against RNA degradation enzymes and extreme environmental conditions. miRNAs preservation is facilitated through packaging in lipid vesicles or complex formation with RNA‐binding proteins. Numerous studies have illuminated the roles of miRNAs in diverse physiological processes, including embryonic stem cell differentiation, haematopoietic stem cell proliferation and differentiation and the coordinated development of organ systems. The integration of miRNA profiling, next‐generation sequencing and bioinformatics analysis paves the way for transformative advancements in livestock research and industry. The present review underscores the applications of miRNAs in livestock, showcasing their potential to improve breeding strategies, diagnose diseases and enhance our understanding of fundamental biological processes.
Shoreline restoration including armor removal and log placement affect ecosystem recovery through time
Authors: Des Roches Simone , Accola Kerry L. , Faulkner Hannah S. , Morgan Jason R. , Perla Bianca S. , Metler Maria , Dethier Megan N. , Toft Jason D.
Published: January 2024

The impacts of individual restoration activities, such as the total area covered and specific actions taken, can be difficult to measure because they are typically not performed randomly or independently. In Puget Sound, Washington, United States, removal of hard armor is a primary shoreline restoration measure. The length of armor removed from a beach and additional restoration actions implemented can vary considerably. As such, it is challenging to attribute specific ecological responses to particular actions. We use an extensive collection of sites regularly monitored pre‐ and post‐restoration to explore the success of different extents of armor removal and three supplemental “living shoreline” restoration actions: native vegetation planting, log placement, and sediment supplementation (“nourishment”). We measured five ecological response variables: sediments (percent surface, subsurface gravel), beach logs (count, line width), beach wrack (percent cover, depth), riparian vegetation (percent cover of supratidal, backshore), and supratidal invertebrates (density, richness). Only beach logs were affected by the length of armor removed, whereas wrack increased regardless of length. Invertebrate abundance increased through time only when supplemental vegetation planting did not occur. Placement of logs post armor removal was an impactful supplemental restoration strategy, positively affecting not only the further accumulation of logs, but also the amount of wrack and gravel sediments. Sediment nourishment only affected the proportion of subsurface gravel, which decreased through time in nourished sites. We stress the importance of the thorough monitoring of the ecological effects of living shoreline restoration actions to better understand their role in ecosystem recovery through time.
Discovery of the novel HLA‐A*33:256 allele, a variant of HLA‐A*33:03:01:01, by next‐generation sequencing
Authors: Andryushkina Anna V. , Ananeva Anastasiia , Gusev Oleg , Shagimardanova Elena I.
Published: January 2024

One nucleotide substitution in codon 280 of HLA‐A*33:03:01:01 results in the novel allele, HLA‐A*33:256.
The compression-only behavior of coated microbubbles in a wall restricted flow
Authors: Vlachomitrou Maria , Pelekasis Nikos
Published: January 2024

The impact that the onset of the compression-only behavior of lipid shelled contrast agents bears on their dynamic interaction with a rigid wall under acoustic disturbances is investigated numerically in the context of axisymmetry. Wall presence is seen to not significantly affect the onset of compression-only since it only reduces the time frame required to trigger the effect. The standoff distance from the wall bears no significant effect on the amplitude threshold except that as it is reduced, it favors asymmetry by altering the compressed buckled shape around which the bubble oscillates. Above the amplitude threshold for parametric shape mode excitation, the onset of compression-only in the vicinity of a rigid wall typically interrupts the process of entrapment by reversing the direction of motion via the positive pressure drug that is generated as a result of the emerging concave upwards buckled shapes. Below this amplitude threshold, symmetric shapes or asymmetric shapes that are concave downwards continue to translate towards the wall where they perform saturated trapped pulsations around nearly spherical flattened or concave downwards buckled shapes. The latter shapes perform compression-only type pulsations and arise on the longer time scale required for the destabilization of the nearly spherical initially trapped shapes. Phase diagrams are constructed identifying regions of trapped pulsations, compression-only response, and microbubble collapse, in the parameter space defined by sound amplitude and shell viscoelastic properties.
Machine learning based estimation of hoarseness severity using sustained vowels
Authors: Schraut Tobias , Schützenberger Anne , Arias-Vergara Tomás , Kunduk Melda , Echternach Matthias , Döllinger Michael
Published: January 2024

Auditory perceptual evaluation is considered the gold standard for assessing voice quality, but its reliability is limited due to inter-rater variability and coarse rating scales. This study investigates a continuous, objective approach to evaluate hoarseness severity combining machine learning (ML) and sustained phonation. For this purpose, 635 acoustic recordings of the sustained vowel /a/ and subjective ratings based on the roughness, breathiness, and hoarseness scale were collected from 595 subjects. A total of 50 temporal, spectral, and cepstral features were extracted from each recording and used to identify suitable ML algorithms. Using variance and correlation analysis followed by backward elimination, a subset of relevant features was selected. Recordings were classified into two levels of hoarseness, H<2 and H≥2, yielding a continuous probability score ŷ∈[0,1]. An accuracy of 0.867 and a correlation of 0.805 between the model's predictions and subjective ratings was obtained using only five acoustic features and logistic regression (LR). Further examination of recordings pre- and post-treatment revealed high qualitative agreement with the change in subjectively determined hoarseness levels. Quantitatively, a moderate correlation of 0.567 was obtained. This quantitative approach to hoarseness severity estimation shows promising results and potential for improving the assessment of voice quality.
Breaking Barriers: An Innovative Tool to Assess the National and City-Level Physical Activity Policy Development to Practice Disconnect
Authors: Resendiz Eugen , Ramírez-Varela Andrea , Mejía-Grueso Juliana , Moon Jane , Mitáš Josef , Brownson Ross C. , Salvo Deborah , Pratt Michael
Published: January 2024

Background: Population-level physical activity increases are improbable without intersectoral collaboration across government levels and sectors to develop and implement physical activity promotion policies. This study aims to provide information about the development of the Interaction between National and Local Government Levels in Development and Implementation of Physical Activity Policies Tool (INTEGRATE PA-Pol). A framework was created to examine the development and implementation of national and subnational physical activity policies and the (mis)alignment between government levels. Methods: The work was conducted in 3 phases: (1) a scoping review was carried out to identify local government physical activity promotion policies and instruments for assessing them, (2) an expert group designed 6 questionnaires, and (3) cognitive response testing was employed for validity testing and item modification with a panel of research and policy experts. Results: The INTEGRATE PA-Pol Tool consists of 6 questionnaires assessing how national and subnational governments collaborate to develop and implement physical activity promotion policies. Conclusion: This tool can assist in better understanding the development and implementation of a public policy monitoring system that will allow for benchmarking and priority setting to comprehend how physical activity promotion policies are designed and executed.
An Ego-Involving Motivational Climate Can Trigger Inflammation, a Threat Appraisal, and Basic Psychological Need Frustration in an Achievement Context
Authors: Hogue Candace M.
Published: January 2024

In this experimental investigation, male college students (N = 56; Mage = 19.95 years) who did not yet know how to juggle were randomly assigned to a 30-min instructional juggling session with either a caring, task-involving climate or an ego-involving climate. An inflammatory response to psychosocial stress was assessed via salivary interleukin-6 prior to (t = 0) and following (t = +30, +45, +60 min) the session. Surveys were utilized to examine positive and negative affect prior to the session and affect, psychological needs, challenge and threat appraisals, and perceived ability to juggle following the session. This is the first investigation to show that ego-involving climates can trigger inflammation, along with maladaptive psychological responses. Participants in the caring, task-involving climate responded with greater psychological need satisfaction, resource evaluations, positive affect, and perceived juggling ability. This research suggests there may be important physiological consequences to ego-involving climates, in addition to concerning cognitive, affective, and behavioral responses.
Coherently parallel fiber-optic distributed acoustic sensing using dual Kerr soliton microcombs
Authors: Li Jian-Ting , Chang Bing , Du Jun-Ting , Tan Teng , Geng Yong , Zhou Heng , Liang Yu-Pei , Zhang Hao , Yan Guo-Feng , Ma Ling-Mei , Ran Zeng-Ling , Wang Zi-Nan , Yao Bai-Cheng , Rao Yun-Jiang
Published: January 2024

Fiber-optic distributed acoustic sensing (DAS) has proven to be a revolutionary technology for the detection of seismic and acoustic waves with ultralarge scale and ultrahigh sensitivity, and is widely used in oil/gas industry and intrusion monitoring. Nowadays, the single-frequency laser source in DAS becomes one of the bottlenecks limiting its advance. Here, we report a dual-comb–based coherently parallel DAS concept, enabling linear superposition of sensing signals scaling with the comb-line number to result in unprecedented sensitivity enhancement, straightforward fading suppression, and high-power Brillouin-free transmission that can extend the detection distance considerably. Leveraging 10-line comb pairs, a world-class detection limit of 560 fε/√Hz@1 kHz with 5 m spatial resolution is achieved. Such a combination of dual-comb metrology and DAS technology may open an era of extremely sensitive DAS at the fε/√Hz level, leading to the creation of next-generation distributed geophones and sonars.
Integrative analysis of noncoding mutations identifies the druggable genome in preterm birth
Authors: Wang Cheng , Wang Yuejun Jessie , Ying Lihua , Wong Ronald J. , Quaintance Cecele C. , Hong Xiumei , Neff Norma , Wang Xiaobin , Biggio Joseph R. , Mesiano Sam , Quake Stephen R. , Alvira Cristina M. , Cornfield David N. , Stevenson David K. , Shaw Gary M. , Li Jingjing
Published: January 2024

Preterm birth affects ~10% of pregnancies in the US. Despite familial associations, identifying at-risk genetic loci has been challenging. We built deep learning and graphical models to score mutational effects at base resolution via integrating the pregnant myometrial epigenome and large-scale patient genomes with spontaneous preterm birth (sPTB) from European and African American cohorts. We uncovered previously unidentified sPTB genes that are involved in myometrial muscle relaxation and inflammatory responses and that are regulated by the progesterone receptor near labor onset. We studied genomic variants in these genes in our recruited pregnant women administered progestin prophylaxis. We observed that mutation burden in these genes was predictive of responses to progestin treatment for preterm birth. To advance therapeutic development, we screened ~4000 compounds, identified candidate molecules that affect our identified genes, and experimentally validated their therapeutic effects on regulating labor. Together, our integrative approach revealed the druggable genome in preterm birth and provided a generalizable framework for studying complex diseases.
Global oceanic oxygenation controlled by the Southern Ocean through the last deglaciation
Authors: Wang Yi , Costa Kassandra M. , Lu Wanyi , Hines Sophia K. V. , Nielsen Sune G.
Published: January 2024

Ocean dissolved oxygen (DO) can provide insights on how the marine carbon cycle affects global climate change. However, the net global DO change and the controlling mechanisms remain uncertain through the last deglaciation. Here, we present a globally integrated DO reconstruction using thallium isotopes, corroborating lower global DO during the Last Glacial Maximum [19 to 23 thousand years before the present (ka B.P.)] relative to the Holocene. During the deglaciation, we reveal reoxygenation in the Heinrich Stadial 1 (~14.7 to 18 ka B.P.) and the Younger Dryas (11.7 to 12.9 ka B.P.), with deoxygenation during the Bølling-Allerød (12.9 to 14.7 ka B.P.). The deglacial DO changes were decoupled from North Atlantic Deep Water formation rates and imply that Southern Ocean ventilation controlled ocean oxygen. The coherence between global DO and atmospheric CO
2
on millennial timescales highlights the Southern Ocean’s role in deglacial atmospheric CO
2
rise.
MCJ: A mitochondrial target for cardiac intervention in pulmonary hypertension
Authors: Santamans Ayelén M. , Cicuéndez Beatriz , Mora Alfonso , Villalba-Orero María , Rajlic Sanela , Crespo María , Vo Paula , Jerome Madison , Macías Álvaro , López Juan Antonio , Leiva Magdalena , Rocha Susana F. , León Marta , Rodríguez Elena , Leiva Luis , Pintor Chocano Aránzazu , García Lunar Inés , García-Álvarez Ana , Hernansanz-Agustín Pablo , Peinado Víctor I. , Barberá Joan Albert , Ibañez Borja , Vázquez Jesús , Spinelli Jessica B. , Daiber Andreas , Oliver Eduardo , Sabio Guadalupe
Published: January 2024

Pulmonary hypertension (PH) can affect both pulmonary arterial tree and cardiac function, often leading to right heart failure and death. Despite the urgency, the lack of understanding has limited the development of effective cardiac therapeutic strategies. Our research reveals that MCJ modulates mitochondrial response to chronic hypoxia. MCJ levels elevate under hypoxic conditions, as in lungs of patients affected by COPD, mice exposed to hypoxia, and myocardium from pigs subjected to right ventricular (RV) overload. The absence of MCJ preserves RV function, safeguarding against both cardiac and lung remodeling induced by chronic hypoxia. Cardiac-specific silencing is enough to protect against cardiac dysfunction despite the adverse pulmonary remodeling. Mechanistically, the absence of MCJ triggers a protective preconditioning state mediated by the ROS/mTOR/HIF-1α axis. As a result, it preserves RV systolic function following hypoxia exposure. These discoveries provide a potential avenue to alleviate chronic hypoxia-induced PH, highlighting MCJ as a promising target against this condition.
Sudapyridine (WX-081) antibacterial activity against
Mycobacterium avium
,
Mycobacterium abscessus
, and
Mycobacterium chelonae in vitro
and
in vivo
Authors: Zheng Luyao , Wang Hong , Qi Xueting , Zhang Weiyan , Wang Bin , Fu Lei , Chen Xi , Chen Xiaoyou , Lu Yu
Published: January 2024

Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows anti-tuberculosis and non-tuberculous mycobacteria (NTM) activities but, unlike BDQ, did not prolong QT interval in animal model studies. This study evaluated the antibacterial activity of this novel compound against
Mycobacterium avium
,
Mycobacterium abscessus
, and
Mycobacterium chelonae in vitro
and
in vivo
. The minimum inhibitory concentration (MIC) of WX-081 against three kinds of non-tuberculous mycobacteria (NTM) clinical strains was determined using microplate-based alamarBlue assay (MABA), and the antibacterial activity of WX-081 against NTM in J774A.1 cells and mice was evaluated. MIC ranges of WX-081 against clinical strains of
M. avium
and
M. abscessus
were 0.05–0.94 μg/mL, 0.88–7.22 μg/mL (
M. abscessus
subsp.
abscessus
), and 0.22–8.67 μg/mL (
M. abscessus
subsp.
massiliense
), respectively, which were slightly higher than those of BDQ. For
M. avium
,
M. abscessus
, and
M. chelonae
, WX-081 can reduce the intracellular bacterial load by 0.13–1.18, 0.18–1.50, and 0.17–1.03 log
10
colony forming units (CFU)/mL, respectively, in a concentration-dependent manner. WX-081 has bactericidal activity against three NTM species in mice. WX-081 exhibited anti-NTM activity to the same extent as BDQ both
in vivo
and
in vitro
. WX-081 is a promising clinical candidate and should be studied further in clinical trials.

IMPORTANCE

Due to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. NTM accounted for 11.57% of all mycobacterial isolates in China, with a high detection rate of
Mycobacterium abscessus
,
Mycobacterium avium
, and
Mycobacterium chelonae
during 2000–2019. Treatment of NTM infection is often challenging, as natural resistance to most antibiotics is quite common among different NTM species. Hence, identifying highly active anti-NTM agents is a priority for potent regimen establishment. The pursuit of new drugs to treat multidrug-resistant tuberculosis may also identify some agents with strong activity against NTM. Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the anti-tuberculosis efficacy but eliminates the severe side effects of BDQ. This study initially evaluated the antimicrobial activity of this novel compound against
M. avium
,
M. abscessus
, and
M. chelonae in vitro
, in macrophages and mice, respectively.
Hepatitis B virus evades the immune system by suppressing the NF-κB signaling pathway with DENND2A
Authors: Ide Mayuko , Tabata Noriko , Yonemura Yuko , Murai Kazuhisa , Wang Ying , Ishida Atsuya , Honda Masao , Kaneko Shuichi , Ito Satoru , Yanagawa Hiroshi
Published: January 2024

Overcoming hepatitis B virus (HBV) is a challenging problem because HBV deceives the host immune system. We have found that DENN domain-containing 2A (DENND2A) was essential for HBV maintenance, although its role remains unclear. In this study, we elucidate its function by screening a novel DENND2A-binding peptide, DENP4-3S. DENP4-3S exhibits homology to SAM and SH3 domain-containing protein 1 (SASH1), a scaffold protein involved in Toll-like receptor signaling that promotes proinflammatory cytokine production. We confirmed that DENND2A interacts with SASH1 specifically. Overexpression and knockdown experiments showed that overexpression of DENND2A suppressed the transcriptional activity of NF-κB, and the knockdown of DENND2A promoted it and the production of cytokines and interferons. Here, we constructed a fusion protein (10M-DEN3SN) consisting of an anti-asialoglycoprotein receptor antibody and DENP4-3S to deliver the peptide to hepatocytes specifically. 10M-DEN3SN inhibited the interaction between DENND2A and SASH1, and rescued SASH1 trapped by DENND2A, leading to the upregulation of NF-κB and its downstream signaling. In addition, 10M-DEN3SN suppressed HBV proliferation in PXB chimeric mice. These results with the DENND2A-binding peptide delivered into hepatocytes suggested the involvement of DENND2A, SASH, and NF-κB signaling pathway in the HBV infection and onset of hepatitis. In conclusion, this study indicates that HBV utilizes DENND2A and SASH1 to evade the immune system.

IMPORTANCE

Hepatitis B virus (HBV) is a serious liver infection with no established cure, causing an abnormal host immune response. Here, we identified a novel peptide that interacts with DENN domain-containing 2A (DENND2A), a host factor essential for HBV maintenance. The resulting peptide showed sequence homology, revealing an interaction between DENND2A and the immune system regulator SASH1. This study suggests that DENND2A contributes to HBV infection by suppressing the cellular immune system by inhibiting SASH1. The DENND2A-binding peptide, incorporated into our hepatocyte-specific peptide delivery system, inhibited the DENND2A-SASH1 interaction and promoted the production of cytokines and interferons in cultured hepatocytes. As a consequence, the peptide suppressed HBV proliferation in humanized mice. We report new insights into the role of DENND2A and SASH1 in HBV maintenance and highlight the importance of the immune system.
Ecological study estimating melanoma overdiagnosis in the USA using the lifetime risk method
Authors: Adamson Adewole S , Naik Geetanjali , Jones Mark A , Bell Katy JL
Published: January 2024

Objectives

To quantify the proportion of melanoma diagnoses (invasive and in situ) in the USA that might be overdiagnosed.

Design

In this ecological study, incidence and mortality data were collected from the Surveillance, Epidemiology and End Results 9 registries database. DevCan software was used to calculate the cumulative lifetime risk of being diagnosed with melanoma between 1975 and 2018, with adjustments made for changes in longevity and risk factors over the study period.

Setting

USA.

Participants

White American men and women (1975–2018).

Main outcome measures

The primary outcome was excess lifetime risk of melanoma diagnosis between 1976 and 2018 (adjusted for year 2018 competing mortality and changes in risk factors), which was inferred as likely overdiagnosis. The secondary outcome was an excess lifetime risk of melanoma diagnosis in each year between 1976 and 2018 (adjusted and unadjusted).

Results

Between 1975 and 2018 the adjusted lifetime risk of being diagnosed with melanoma (invasive and in situ) increased from 3.2% (1 in 31) to 6.4% (1 in 16) among white men, and from 1.6% (1 in 63) to 4.5% (1 in 22) among white women. Over the same period, the adjusted lifetime risk of being diagnosed with melanoma in situ increased from 0.17% (1 in 588) to 2.7% (1 in 37) in white men and 0.08% (1 in 1250) to 2.0% (1 in 50) in white women. An estimated 49.7% of melanomas diagnosed in white men and 64.6% in white women were overdiagnosed in 2018. Among people diagnosed with melanomas in situ, 89.4% of white men and 85.4% of white women were likely overdiagnosed in 2018.

Conclusions

Melanoma overdiagnosis among white Americans is significant and increasing over time with an estimated 44 000 overdiagnosed in men and 39 000 in women in 2018. A large proportion of overdiagnosed melanomas are in situ cancers, pointing to a potential focus for intervention.
Rapid review methods series: Guidance on the use of supportive software
Authors: Affengruber Lisa , Nussbaumer-Streit Barbara , Hamel Candyce , Van der Maten Miriam , Thomas James , Mavergames Chris , Spijker Rene , Gartlehner Gerald
Published: January 2024

This paper is part of a series of methodological guidance from the Cochrane Rapid Reviews Methods Group. Rapid reviews (RRs) use modified systematic review methods to accelerate the review process while maintaining systematic, transparent and reproducible methods. This paper guides how to use supportive software for RRs.

We strongly encourage the use of supportive software throughout RR production. Specifically, we recommend (1) using collaborative online platforms that enable working in parallel, allow for real-time project management and centralise review details; (2) using automation software to support, but not entirely replace a human reviewer and human judgement and (3) being transparent in reporting the methodology and potential risk for bias due to the use of supportive software.
Development of the Reporting Infographics and Visual Abstracts of Comparative studies (RIVA-C) checklist and guide
Authors: Zadro Joshua R , Ferreira Giovanni E , Stahl-Timmins Will , Egger Veronika , Elkins Mark R , Gamble Andrew R , O'Keeffe Mary , McCaffery Kirsten J , Harris Ian A , Ardern Clare L , West Courtney A , Maher Chris G , Hoffmann Tammy C
Published: January 2024

People often use infographics (also called visual or graphical abstracts) as a substitute for reading the full text of an article. This is a concern because most infographics do not present sufficient information to interpret the research appropriately and guide wise health decisions. The Reporting Infographics and Visual Abstracts of Comparative studies (RIVA-C) checklist and guide aims to improve the completeness with which research findings of comparative studies are communicated and avoid research findings being misinterpreted if readers do not refer to the full text. The primary audience for the RIVA-C checklist and guide is developers of infographics that summarise comparative studies of health and medical interventions. The need for the RIVA-C checklist and guide was identified by a survey of how people use infographics. Possible checklist items were informed by a systematic review of how infographics report research. We then conducted a two-round, modified Delphi survey of 92 infographic developers/designers, researchers, health professionals and other key stakeholders. The final checklist includes 10 items. Accompanying explanation and both text and graphical examples linked to the items were developed and pilot tested over a 6-month period. The RIVA-C checklist and guide was designed to facilitate the creation of clear, transparent and sufficiently detailed infographics which summarise comparative studies of health and medical interventions. Accurate infographics can ensure research findings are communicated appropriately and not misinterpreted. By capturing the perspectives of a wide range of end users (eg, authors, informatics editors, journal editors, consumers), we are hopeful of rapid endorsement and implementation of RIVA-C.
Time to death and predictors of mortality among asphyxiated neonates in southwest Ethiopia, 2022: prospective cohort study
Authors: Kebede Belete Fenta , Biyazin Tesfa Tsegaw , Yetwale Hiwot Aynalem , Mulu Kassa Kindie , Adugnaw Emebet , Mihretu Esmelalem , Sewmehone Enatfenta , Genie Yalemtsehay Dagnaw
Published: January 2024

Objective

This study aimed to determine the time to death and predictors of mortality among asphyxiated neonates admitted to public hospitals in the southwest region of Ethiopia.

Design

An institution-based prospective cohort study was conducted.

Setting

Public hospitals in southwest Ethiopia.

Participants

A total of 144 asphyxiated neonates, who were admitted to the neonatal intensive care unit, and their mothers participated from March 2022 to 30 September 2022. Data were entered into EpiData V.4.4.2.1 and exported to STATA V.16 for analysis. The Cox proportional hazards model using bivariate (p<0.25) and multivariate (p<0.05) analyses was used to identify the predictors of mortality. The median survival time was estimated using Kaplan-Meier survival estimates.

Primary outcome

Time to death from asphyxia and its predictors in neonates.

Results

The mortality incidence rate of asphyxiated neonates was 9.1 deaths per 1000 person-days of observation (95% CI: 7.11 to 11.52) with a median survival time of 8 days, and 45.83% (95% CI: 37.81% to 54.08%) of asphyxiated neonates died. Being male (adjusted HR (AHR) 0.32 (95% CI: 0.14 to 0.76)), neonatal sepsis (AHR 0.321 (95% CI: 0.13 to 0.77)), not receiving kangaroo mother care (AHR 0.16 (95% CI: 0. 07 to 0.39)) and vaginal delivery (AHR 0.39 (95% CI: 0.16 to 0.95)) were independent predictors of mortality of asphyxiated neonates.

Conclusions

In this study, asphyxiated neonates had a higher incidence of mortality with a median survival time of only 8 days. Being male, vaginal delivery, not receiving kangaroo mother care and comorbidities such as neonatal sepsis were independent predictors of mortality among asphyxiated neonates. Therefore, healthcare providers and other stakeholders should provide timely initiation of advanced diagnosis and appropriate therapeutic interventions for neonates with asphyxia to reduce neonatal mortality.
Challenges and knowledge gaps in the management of non-tuberculous mycobacterial pulmonary disease in sub-Saharan African countries with a high tuberculosis burden: a scoping review
Authors: Abbew Elizabeth Tabitha , Lorent Natalie , Mesic Anita , Wachinou Ablo Prudence , Obiri-Yeboah Dorcas , Decroo Tom , Rigouts Leen , Lynen Lutgarde
Published: January 2024

Introduction

In sub-Saharan African (SSA) countries endemic for tuberculosis (TB), previous TB is a significant risk factor for non-tuberculous mycobacterial pulmonary disease (NTM-PD). The deployment of GeneXpert MTB/RIF in pulmonary TB diagnostic work-up regularly identifies symptomatic patients with a positive smear microscopy but negative GeneXpert, indicative of NTM presence. This scoping review outlines recent evidence for NTM-PD diagnosis and management in SSA.

Objective

The review’s objective was to outline the risk factors, available diagnostics, management options and outcomes of NTM-PD in high-burden TB settings in SSA using the population-concept-context framework.

Design and data sources

We searched existing literature from PubMed, Web of Science, African Journals Online, Google Scholar and grey literature. Studies published between January 2005 and December 2022 were retained. Data were extracted into Rayyan software and Mendeley and summarised using Excel.

Results

We identified 785 potential articles, of which 105 were included in the full-text review, with 7 papers retained. Included articles used international criteria for diagnosing NTM-PD. Multiple papers were excluded due to non-application of the criteria, suggesting challenging application in the SSA setting. Identified risk factors include previous TB, smoking and mining. Most commonly, chest radiography and not CT was used for the radiological diagnosis of PD, which may miss early changes related to NTM-PD. Molecular methods for NTM species identification were employed in research settings, usually at referral centres, but were unavailable for routine care. Most studies did not report a standardised approach to treatment and they were not offered treatment for the specific disease, marking a lack of guidance in treatment decision-making. When treatment was provided, the outcome was often not reported due to the lack of implementation of standardised outcome definitions.

Conclusions

These outlined challenges present a unique opportunity for researchers to undertake further studies in NTM-PD and proffer solutions more applicable to SSA.
HIP fracture Supplemental Therapy to Enhance Recovery (HIPSTER): a protocol for a randomised controlled trial
Authors: Kimmel Lara A , Raper Eleanor , Harris Ian A , Ackerman Ilana N , Page Richard , Naylor Justine M , Burge Angela T , Hepworth Graham , Harris Anthony , Woode Maame Esi , Gabbe Belinda J , Ekegren Christina L , Holland Anne E
Published: January 2024

Introduction

Hip fractures result in substantial health impacts for patients and costs to health systems. Many patients require prolonged hospital stays and up to 60% do not regain their prefracture level of mobility within 1 year. Physical rehabilitation plays a key role in regaining physical function and independence; however, there are no recommendations regarding the optimal intensity. This study aims to compare the clinical efficacy and cost-effectiveness of early intensive in-hospital physiotherapy compared with usual care in patients who have had surgery following a hip fracture.

Methods and analysis

This two-arm randomised, controlled, assessor-blinded trial will recruit 620 participants who have had surgery following a hip fracture from eight hospitals. Participants will be randomised 1:1 to receive usual care (physiotherapy according to usual practice at the site) or intensive physiotherapy in the hospital over the first 7 days following surgery (two additional sessions per day, one delivered by a physiotherapist and the other by an allied health assistant). The primary outcome is the total hospital length of stay, measured from the date of hospital admission to the date of hospital discharge, including both acute and subacute hospital days. Secondary outcomes are functional mobility, health-related quality of life, concerns about falling, discharge destination, proportion of patients remaining in hospital at 30 days, return to preadmission mobility and residence at 120 days and adverse events. Twelve months of follow-up will capture data on healthcare utilisation. A cost-effectiveness evaluation will be undertaken, and a process evaluation will document barriers and facilitators to implementation.

Ethics and dissemination

The Alfred Hospital Ethics Committee has approved this protocol. The trial findings will be published in peer-reviewed journals, submitted for presentation at conferences and disseminated to patients and carers.

Trial registration number

ACTRN12622001442796.
Interventions to improve continence for children and young people with neurodisability: a national survey of practitioner and family perspectives and experiences
Authors: Eke Helen , Ball Susan , Allinson Annette , Anderson Rob , Hunt Harriet , Hutton Eve , Lindsay Claire , Logan Stuart , Madden Nicholas , Melluish Julia , Richardson Davina , Rogers June , Thompson Coon Jo , Whear Rebecca , Wright Anne , Morris Christopher
Published: January 2024

Objective

Describe families’ experiences of interventions to improve continence in children and young people with neurodisability, and health professionals’ and school and social care staff’s perspectives regarding factors affecting intervention use.

Design

Four online surveys were developed and advertised to parent carers, young people with neurodisability, health professionals and school and social care staff, via societies, charities, professional contacts, schools, local authorities, and national parent carer and family forums, who shared invitations with their networks. Survey questions explored: difficulties helping children and young people use interventions; acceptability of interventions and waiting times; ease of use and availability of interventions, and facilitators and barriers to improving continence.

Results

1028 parent carers, 26 young people, 352 health professionals and 202 school and social care staff registered to participate. Completed surveys were received from 579 (56.3%) parent carers, 20 (77%) young people, 193 (54.8%) health professionals, and 119 (58.9%) school and social care staff. Common parent carer-reported difficulties in using interventions to help their children and young people to learn to use the toilet included their child’s lack of understanding about what was required (reported by 337 of 556 (60.6%) parent carers who completed question) and their child’s lack of willingness (343 of 556, 61.7%). Almost all (142 of 156, 91%) health professionals reported lack of funding and resources as barriers to provision of continence services. Many young people (14 of 19, 74%) were unhappy using toilet facilities while out and about.

Conclusions

Perceptions that children lack understanding and willingness, and inadequate facilities impact the implementation of toileting interventions for children and young people with neurodisability. Greater understanding is needed for children to learn developmentally appropriate toileting skills. Further research is recommended around availability and acceptability of interventions to ensure quality of life is unaffected.