bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Bortezomib for Treating Anti-Interferon-Gamma Autoantibody-Associated Adult-Onset Immunodeficiency Syndrome
Authors: Angkasekwinai Nasikarn , Suputtamongkol Yupin , Tantibhedhyangkul Wiwit , Onlamoon Nattawat , Phoompoung Pakpoom , Pithukpakorn Manop , Karuphong Ekkapun , Pusuwan Pawana , Angkasekwinai Pornpimon
Published: November 2023

Background

Currently, there is no effective treatment for adult-onset immunodeficiency (AOID) syndrome with anti-interferon-gamma autoantibodies (anti-IFN-γ-auto-Abs). This study aimed to investigate the effectiveness of bortezomib (BTZ) for decreasing anti-IFN-γ-auto-Abs.

Methods

A pre- and post-intervention study was conducted from February 2017 through June 2019 at Siriraj Hospital (Bangkok, Thailand). Five patients were invited to receive once-weekly BTZ (1.3 mg/m2 body surface area) subcutaneously for 8 weeks followed by oral cyclophosphamide (1 mg/kg/d) for 4 months. The primary outcomes were the difference in antibody level at 8 and 48 weeks compared with baseline and the incidence of serious adverse events (AEs). The secondary outcome was the occurrence of opportunistic infections (OIs) during the 72 weeks after starting BTZ.

Results

The median patient age was 46 years (range, 34–53). All patients had 3–5 OIs prior to enrollment. All patients were receiving antimycobacterial agents for treatment of nontuberculous mycobacterial infection at enrollment. There was no significant difference in the mean optical density of auto-Abs at 8 weeks (3.73 ± 0.72) or 48 weeks (3.74 ± 0.53) compared with baseline (3.84 ± 0.49; P = .336 and P = .555, respectively). However, after serum dilution, the antibody titer nonsignificantly decreased 8–16 weeks after BTZ initiation (P = .345). Ten OIs were observed 24–72 weeks after BTZ initiation.

Conclusions

Treatment with BTZ followed by cyclophosphamide yielded no significant decrease in antibody titer levels, and 10 OIs were observed during 24–72 weeks of BTZ treatment. No serious AEs were observed. Combining rituximab with BTZ is likely necessary to prevent generation of new autoantibody-producing plasma cells.

Clinical Trials Registration. NCT03103555.
Brain Abscess Caused by Oral Cavity Bacteria: A Nationwide, Population-based Cohort Study
Authors: Bodilsen Jacob , Mariager Theis , Duerlund Lærke Storgaard , Storgaard Merete , Larsen Lykke , Brandt Christian Thomas , Hansen Birgitte Rønde , Wiese Lothar , Omland Lars Haukali , Nielsen Henrik ,   Danish Study Group of Infections of the Brain, Storgaard Merete , Larsen Lykke , Hansen Birgitte Rønde , Andersen Christian Østergaard , Wiese Lothar , Jepsen Micha Phill Grønholm , Mens Helene , Lüttichau Hans Rudolf , Nielsen Henrik , Bodilsen Jacob
Published: November 2023

Background

Oral cavity bacteria are the most frequent etiology of brain abscess. Yet, data on the clinical presentation and outcome are scarce.

Methods

We performed a nationwide, population-based study comprising all adults (aged ≥18 years) with brain abscess due to oral cavity bacteria in Denmark from 2007 through 2020. Prognostic factors for unfavorable outcome (Glasgow outcome scale, 1–4) were examined using modified Poisson regression to compute adjusted relative risks (RRs) with 95% confidence intervals (CIs).

Results

Among 287 identified patients, the median age was 58 years (interquartile range, 47–66), and 96 of 287 (33%) were female. Preexisting functional impairment was absent or mild in 253 of 280 (90%), and risk factors for brain abscess included immunocompromise in 95 of 287 (33%), dental infection in 68 of 287 (24%), and ear–nose–throat infection in 33 of 287 (12%). Overall, a neurological deficit was present in 246 of 276 (86%) and in combination with headache and fever in 64 of 287 (22%). Identified microorganisms were primarily the Streptococcus anginosus group, Fusobacterium, Actinomyces, and Aggregatibacter spp., and 117 of 287 (41%) were polymicrobial. Unfavorable outcome occurred in 92 of 246 (37%) at 6 months after discharge and was associated with antibiotics before neurosurgery (RR, 3.28; 95% CI, 1.53–7.04), rupture (RR, 1.89; 95% CI, 1.34–2.65), and immunocompromise (RR, 1.80; 95% CI, 1.29–2.51), but not with specific targeted antibiotic regimens. Identified dental infection was associated with favorable prognosis (RR, 0.58; 95% CI, .36–.93).

Conclusions

Brain abscess due to oral cavity bacteria often occurred in previously healthy individuals without predisposing dental infections. Important risk factors for unfavorable outcome were rupture and immunocompromise. However, outcome was not associated with specific antibiotic regimens supporting carbapenem-sparing strategies.
Incremental versus conventional haemodialysis in end-stage kidney disease: a systematic review and meta-analysis
Authors: Takkavatakarn Kullaya , Jintanapramote Kavita , Phannajit Jeerath , Praditpornsilpa Kearkiat , Eiam-Ong Somchai , Susantitaphong Paweena
Published: November 2023

Background

Appropriate dialysis prescription in the transitional setting from chronic kidney disease to end-stage kidney disease is still challenging. Conventional thrice-weekly haemodialysis (HD) might be associated with rapid loss of residual kidney function (RKF) and high mortality. The benefits and risks of incremental HD compared with conventional HD were explored in this systematic review and meta-analysis.

Methods

We searched MEDLINE, Scopus and Cochrane Central Register of Controlled Trials up to April 2023 for studies that compared the impacts of incremental (once- or twice-weekly HD) and conventional thrice-weekly HD on cardiovascular events, RKF, vascular access complications, quality of life, hospitalization and mortality.

Results

A total of 36 articles (138 939 participants) were included in this meta-analysis. The mortality rate and cardiovascular events were similar between incremental and conventional HD {odds ratio [OR] 0.87 [95% confidence interval (CI)] 0.72–1.04 and OR 0.67 [95% CI 0.43–1.05], respectively}. However, hospitalization and loss of RKF were significantly lower in patients treated with incremental HD [OR 0.44 (95% CI 0.27–0.72) and OR 0.31 (95% CI 0.25–0.39), respectively]. In a sensitivity analysis that included studies restricted to those with RKF or urine output criteria, incremental HD had significantly lower cardiovascular events [OR 0.22 (95% CI 0.08–0.63)] and mortality [OR 0.54 (95% CI 0.37–0.79)]. Vascular access complications, hyperkalaemia and volume overload were not statistically different between groups.

Conclusions

Incremental HD has been shown to be safe and may provide superior benefits in clinical outcomes, particularly in appropriately selected patients. Large-scale randomized controlled trials are required to confirm these potential advantages.
API Recommendation For Mashup Creation: A Comprehensive Survey
Authors: Alhosaini Hadeel , Alharbi Sultan , Wang Xianzhi , Xu Guandong
Published: November 2023

Mashups are web applications that expedite software development by reusing existing resources through integrating multiple application programming interfaces (APIs). Recommending the appropriate APIs plays a critical role in assisting developers in building such web applications easily and efficiently. The proliferation of publicly available APIs on the Internet has inspired the community to adopt various models to accomplish the recommendation task. Until present, considerable efforts have been made to recommend the optimal set of APIs, delivering fruitful results and achieving varying recommendation performance. This paper presents a timely review on the topic of API recommendations for mashup creation. Specifically, we investigate and compare not only traditional data mining approaches and recommendation techniques but also more recent approaches based on network representation learning and deep learning techniques. By analyzing the merits and pitfalls of existing approaches, we pinpoint a few promising directions to address the remaining challenges in the current research. This survey provides a timely comprehensive review of the API recommendation research and could be a useful reference for relevant researchers and practitioners.
Role of conduction system pacing in ablate and pace strategies for atrial fibrillation
Authors: Tung Roderick , Burri Haran
Published: November 2023

With the advent of conduction system pacing, the threshold for performing ‘ablate and pace’ procedures for atrial fibrillation has gone down markedly in many centres due to the ability to provide a simple and physiological means of pacing the ventricles. This article reviews the technical considerations for this strategy as well as the current evidence, recognized indications, and future perspectives.
On a collision course: fatal motorcycle and bicycle accidents of adolescents in Finland from 2008 to 2019
Authors: Unkuri Jani , Salminen Päivi , Sihvola Niina , Kosola Silja
Published: November 2023

Background

Transport injuries are a major cause of mortality among adolescents. Our aim was to evaluate the circumstances and trauma associated with fatal accidents involving adolescents and two-wheeled vehicles.

Methods

We analyzed retrospective data from the Finnish Crash Data Institute from 2008 to 2019 involving 10- to 24-year-old victims of fatal traffic accidents who were injured while riding a bicycle, moped or motorcycle. We collected data on patient characteristics, accident circumstances and possible treatment. These fatalities were compared with national mortality rates among the respective age groups.

Results

We identified 147 fatalities over the 12-year period involving 20 bicycle, 50 moped and 77 motorcycle riders. Most accidents involved males (n = 121, 82%). Less than half of vehicles were in good condition (46%); motorized vehicles were often illegally tuned (37%) or had tire problems (31%). Most of the accidents were collisions with another vehicle (n = 99, 67%) or other objects (n = 35, 24%). In 94% of cases, the Injury Severity Score was >25. Head injury was the most common cause of death (62%). Among 15-year-olds, every fifth death was due to accidents on two-wheeled vehicles.

Conclusions

Fatal transport accidents among adolescents comprise several elements that should be incorporated into driver’s education and in case of minors, also communicated to parents. These include the condition of the vehicle, proper helmet use and effects of speed on both control of the vehicle and the consequences of a possible collision.
The impact of helping experience on helper life-history and fitness in a cooperatively breeding bird
Authors: Chesterton Ellie , Sparks Alexandra M , Burke Terry , Komdeur Jan , Richardson David S , Dugdale Hannah L
Published: November 2023

Cooperative breeding occurs when helpers provide alloparental care to the offspring of a breeding pair. One hypothesis of why helping occurs is that helpers gain valuable skills that may increase their own future reproductive success. However, research typically focuses on the effect of helping on short-term measures of reproductive success. Fewer studies have considered how helping affects long-term fitness measures. Here, we analyze how helping experience affects key breeding and fitness-related parameters in the Seychelles warbler (Acrocephalus sechellensis). Importantly, we control for females that have cobred (reproduced as a subordinate by laying an egg within a territory in which they are not a dominant breeder), as they already have experience with direct reproduction. Helping experience had no significant association with any of the metrics considered, except that helpers had an older age at first dominance. Accounting for helping experience, females that had cobred produced more adult offspring (≥1 year) after acquiring dominance and had a higher lifetime reproductive success (LRS) than females that had never cobred. Our results suggest that, in the Seychelles warbler, helping experience alone does not increase the fitness of helpers in any of the metrics considered, and highlights the importance of separating the effects of helping from cobreeding. Our findings also emphasize the importance of analyzing the effect of helping at various life-history stages, as higher short-term fitness may not translate to an overall increase in LRS.
Evolutionary Genomics of Sister Species Differing in Effective Population Sizes and Recombination Rates
Authors: Ye Zhiqiang , Pfrender Michael E , Lynch Michael
Published: November 2023

Studies of closely related species with known ecological differences provide exceptional opportunities for understanding the genetic mechanisms of evolution. In this study, we compared population-genomics data between Daphnia pulex and Daphnia pulicaria, two reproductively compatible sister species experiencing ecological speciation, the first largely confined to intermittent ponds and the second to permanent lakes in the same geographic region. Daphnia pulicaria has lower genome-wide nucleotide diversity, a smaller effective population size, a higher incidence of private alleles, and a substantially more linkage disequilibrium than D. pulex. Positively selected genes in D. pulicaria are enriched in potentially aging-related categories such as cellular homeostasis, which may explain the extended life span in D. pulicaria. We also found that opsin-related genes, which may mediate photoperiodic responses, are under different selection pressures in these two species. Genes involved in mitochondrial functions, ribosomes, and responses to environmental stimuli are found to be under positive selection in both species. Additionally, we found that the two species have similar average evolutionary rates at the DNA-sequence level, although approximately 160 genes have significantly different rates in the two lineages. Our results provide insights into the physiological traits that differ within this regionally sympatric sister-species pair that occupies unique microhabitats.
High-resolution mascon solutions reveal glacier-scale mass changes over the Greenland Ice Sheet from 2002 to 2022
Authors: Wang Wei , Shen Yunzhong , Chen Qiujie , Wang Fengwei
Published: November 2023

As the main contributor to global sea-level rise, the Greenland Ice Sheet (GrIS) has undergone significant mass change over the last two decades. The satellite mission of GRACE (Gravity Recovery And Climate Experiment) and its follow-on mission (GRACE-FO) provide accurate observations but low-spatial resolution. In contrast, satellite altimetry provides observations at a high-spatial resolution but with large uncertainties, limiting the understanding of glacier-scale mass change. To derive accurate and high-spatial resolution mass change estimates from GRACE/GRACE-FO observations, we present a novel constraint mascon method in which the regularization matrix is constructed with the signal variances from satellite altimetry. Based on the proposed method, we derive a series of high-resolution (25 km × 25 km) monthly mascon solutions from 2002 April to September. The glacier-scale estimates from the input–output method agree better with those from our mascon solutions than those from the global mascons of CSR (Center for Space Research, the University of Texas), JPL (Jet Propulsion Laboratory), and GSFC (Goddard Space Flight Center), with a higher linear regression coefficient of 0.71. Benefitting from the greatly improved spatial resolution, our estimates provide the first accurate monthly glacier-scale mass change estimates from GRACE/GRACE-FO observations over the GrIS, to our knowledge. The results show that 20 of the 260 glaciers contributed to more than 42 per cent of the ice loss in the GrIS from 2002 to 2022. Most strikingly, the mass loss of Jakobshavn Isbrae was the most significant at –18.7 ± 0.05 Gt yr−1, accounting for 7.4 per cent of the total in the GrIS during the study period. Furthermore, we find that the SMB (surface mass balance) and ice-dynamics-related mass changes contribute nearly equally to the observed mass changes, but the corresponding spatiotemporal characteristics differ. SMB contributed the most to the mass change in 2019, while ice dynamics played the most dominant role in 2018. Moreover, the SMB effect is widespread, and ice-dynamics-related mass loss is mainly concentrated in five small areas.
A detailed analysis of stochastic models applied to temporal gravity field recovery with GRACE observations
Authors: Yu Biao , You Wei , Kusche Jürgen , Fan Dongming , Su Yong , Zhang Jiahui
Published: November 2023

In this study, we analysed the impacts of errors in background force models and observed non-gravitational forces on the pseudo-observations (pre-fits) during gravity field recovery based on the Gravity Recovery and Climate Experiment (GRACE) satellite gravity mission. To reduce these effects, we introduced the stochastic parameters into the functional model of the variational equation integration approach to absorb this type of noise contribution. Simultaneously, the prior variances of observed orbits and K-band range rates used in traditional method are re-estimated with least-squares variance component estimation (LS-VCE) after considering these stochastic parameters. To improve the computing efficiency, a modified method of the calculation of sensitivity matrices related to the introduced stochastic parameters is proposed. Compared to the method of variation of constants widely used in the precise orbit determination and gravity field recovery, the modified method decreases the computational time of these matrices by about four times. Furthermore, an efficient LS-VCE algorithm is derived in a more generalized case. The efficient algorithm only costs 1 per cent of the time of the unoptimized method. With the GRACE data, we analysed the benefits of these refinements in gravity field recovery, and the results show that these improvements can mitigate the impacts of errors in background force models and accelerometer data on recovered gravity field models, especially in the high-degree signals. Furthermore, the quality of results has less dependence on parametrization.
Using queueing models as a decision support tool in allocating point-of-care HIV viral load testing machines in Kisumu County, Kenya
Authors: Wang Yinsheng , Wagner Anjuli D , Liu Shan , Kingwara Leonard , Oyaro Patrick , Brown Everlyne , Karauki Enerikah , Yongo Nashon , Bowen Nancy , Kiiru John , Hassan Shukri , Patel Rena
Published: November 2023

Point-of-care (POC) technologies—including HIV viral load (VL) monitoring—are expanding globally, including in resource-limited settings. Modelling could allow decision-makers to consider the optimal strategy(ies) to maximize coverage and access, minimize turnaround time (TAT) and minimize cost with limited machines. Informed by formative qualitative focus group discussions with stakeholders focused on model inputs, outputs and format, we created an optimization model incorporating queueing theory and solved it using integer programming methods to reflect HIV VL monitoring in Kisumu County, Kenya. We modelled three scenarios for sample processing: (1) centralized laboratories only, (2) centralized labs with 7 existing POC ‘hub’ facilities and (3) centralized labs with 7 existing and 1–7 new ‘hub’ facilities. We calculated total TAT using the existing referral network for scenario 1 and solved for the optimal referral network by minimizing TAT for scenarios 2 and 3. We conducted one-way sensitivity analyses, including distributional fairness in each sub-county. Through two focus groups, stakeholders endorsed the provisionally selected model inputs, outputs and format with modifications incorporated during model-building. In all three scenarios, the largest component of TAT was time spent at a facility awaiting sample batching and transport (scenarios 1–3: 78.7%, 89.9%, 91.8%) and waiting time at the testing site (18.7%, 8.7%, 7.5%); transportation time contributed minimally to overall time (2.6%, 1.3%, 0.7%). In scenario 1, the average TAT was 39.8 h (SD: 2.9), with 1077 h that samples spent cumulatively in the VL processing system. In scenario 2, the average TAT decreased to 33.8 h (SD: 4.8), totalling 430 h. In scenario 3, the average TAT decreased nearly monotonically with each new machine to 31.1 h (SD: 8.4) and 346 total hours. Frequency of sample batching and processing rate most impacted TAT, and inclusion of distributional fairness minimally impacted TAT. In conclusion, a stakeholder-informed resource allocation model identified optimal POC VL hub allocations and referral networks. Using existing—and adding new—POC machines could markedly decrease TAT, as could operational changes.
Vaping industry participation standards in health organizations: an exploratory policy content analysis
Authors: Haklar Isabelle , Stephens Jacqueline , Bowden Jacqueline , Trigg Joshua
Published: November 2023

The vaping industry has been found to employ similar tactics to tobacco industry actors to seek credibility and distort the scientific evidence base around the health harms of nicotine vaping products. As vaping industry interests undermine vaping control efforts, safeguards are necessary to protect against this influence. We aimed to examine health organizations’ policies on vaping industry participation in their activities in Australia. A descriptive approach integrating policy analysis and key informant surveys was used to obtain vaping industry participation information from health research stakeholders. Descriptive statistics on organization type, policy document type, policy document industry focus (tobacco or vaping) and respondent role and responsibility were collected. We used framework analysis to identify themes describing organizational allowances, constraints, and rationale for vaping industry research participation. Relevant health organizations were identified within Australia for policy searching (n = 156), which identified 47 unique policy documents. After contacting 267 key stakeholders from eligible organizations, 31 survey responses were analysed. Research organizations and universities were highly represented in both the policy and survey data. Most health research stakeholders recognized that vaping industry interests counteract public health priorities and opposed vaping industry participation. However, many organizations lacked clear, vaping industry-specific participation policies. To protect the integrity of the emerging evidence base around vaping harms which inform vaping policy, health organizations require strong, comprehensive policies to resist vaping industry participation in research.
Age- and region-dependent cortical excitability in the zQ175 Huntington disease mouse model
Authors: Wang Yundi , Ramandi Daniel , Sepers Marja D , Mackay James P , Raymond Lynn A
Published: November 2023

The neurodegenerative disorder, Huntington disease (HD), manifests as disorders of movement, cognition and mood. Although studies report abnormal corticostriatal synaptic function early in HD mouse models, less is known about cortical–cortical activity across brain regions and disease stages. Recently, we reported enhanced mesoscale spread of cortical responses to sensory stimulation in vivo at early-manifest stages of two HD mouse models. Here, we investigated cortical excitability of zQ175 HD-model mice compared to their wild-type littermates across different cell types, ages and/or cortical regions using ex vivo electrophysiology. Cortical pyramidal neurons (CPNs) in somatosensory cortex of zQ175 mice showed intrinsic hyper-excitability at 3–4 months, but hypo-excitability at early-manifest stage (8–9 months); reduced frequency of spontaneous excitatory postsynaptic currents (sEPSCs) was seen at both ages. In contrast, motor cortex CPNs in early-manifest zQ175 mice showed increased intrinsic excitability and sEPSC frequency. Large-amplitude excitatory discharges recorded from CPNs in early-manifest zQ175 mice showed increased frequency only in somatosensory cortex, suggesting the intrinsic hypo-excitability of these CPNs may be compensatory against cortical network hyper-excitability. Similarly, in early-manifest zQ175 mice, region-dependent differences were seen in fast-spiking interneurons (FSIs): somatosensory but not motor FSIs from early-manifest zQ175 mice had reduced intrinsic excitability. Moreover, CPNs showed decreased frequency of spontaneous inhibitory postsynaptic currents and increased excitatory-inhibitory (E-I) balance of evoked synaptic currents in somatosensory cortex. Aberrant large-amplitude discharges and reduced inhibitory drive may therefore underlie E-I imbalances that result in circuit changes and synaptic dysfunction in early-manifest HD.
A transcriptomics-based drug repositioning approach to identify drugs with similar activities for the treatment of muscle pathologies in spinal muscular atrophy (SMA) models
Authors: Hoolachan Joseph M , McCallion Eve , Sutton Emma R , Çetin Özge , Pacheco-Torres Paloma , Dimitriadi Maria , Sari Suat , Miller Gavin J , Okoh Magnus , Walter Lisa M , Claus Peter , Wood Matthew J A , Tonge Daniel P , Bowerman Melissa
Published: November 2023

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by the reduction of survival of motor neuron (SMN) protein levels. Although three SMN-augmentation therapies are clinically approved that significantly slow down disease progression, they are unfortunately not cures. Thus, complementary SMN-independent therapies that can target key SMA pathologies and that can support the clinically approved SMN-dependent drugs are the forefront of therapeutic development. We have previously demonstrated that prednisolone, a synthetic glucocorticoid (GC) improved muscle health and survival in severe Smn−/−;SMN2 and intermediate Smn2B/− SMA mice. However, long-term administration of prednisolone can promote myopathy. We thus wanted to identify genes and pathways targeted by prednisolone in skeletal muscle to discover clinically approved drugs that are predicted to emulate prednisolone’s activities. Using an RNA-sequencing, bioinformatics, and drug repositioning pipeline on skeletal muscle from symptomatic prednisolone-treated and untreated Smn−/−; SMN2 SMA and Smn+/−; SMN2 healthy mice, we identified molecular targets linked to prednisolone’s ameliorative effects and a list of 580 drug candidates with similar predicted activities. Two of these candidates, metformin and oxandrolone, were further investigated in SMA cellular and animal models, which highlighted that these compounds do not have the same ameliorative effects on SMA phenotypes as prednisolone; however, a number of other important drug targets remain. Overall, our work further supports the usefulness of prednisolone’s potential as a second-generation therapy for SMA, identifies a list of potential SMA drug treatments and highlights improvements for future transcriptomic-based drug repositioning studies in SMA.
Twenty years’ experience of type B aortic dissections: a population-based national registry study from Finland
Authors: Toimela Juhana Mikael , Sedha Jagdeep , Hedman Marja , Valtola Antti , Selander Tuomas , Husso Annastiina
Published: November 2023

OBJECTIVES

The objective of this study was to investigate the incidence, treatment and survival of Stanford type B aortic dissection (BTAD) during 20 years in the Finnish population.

METHODS

Data collection was made from the Nationwide Care Register for Health Care, Finnish National Institute for Health and Welfare. All patients over 15 years of age with BTAD from 2000 to 2019 were included in the study. A data search of the Registry of Death Cause (Statistic Finland) was carried out to identify the date and cause of death.

RESULTS

There were 1742 cases of BTAD during the study period. BTAD represented 45.6% of all aortic dissections leading to hospital admission. Incidence for BTAD was 1.62 per 100 000 inhabitants per year. The median survival was 12.7 years [95% confidence interval (CI) 9.63–14.7], 12.4 years (95% CI 10.5–14.4) and 8.6 years (95% CI 7.5–9.7) for patients treated with thoracic endovascular aortic repair (TEVAR), surgery and medical treatment (MT), respectively. Survival was significantly better after TEVAR and surgery, compared to MT only (P < 0.001). Age-adjusted survival was significantly better after TEVAR compared to patients treated with MT or surgery (hazard ratio 0.578, 95% CI 0.420–0.794, P < 0.001). Aortic-related death was the most common cause of death in all groups (41%).

CONCLUSIONS

The incidence of BTAD seems to be similar in the Finnish population compared to other populational studies. Patients treated with TEVAR had significantly better survival compared to other patients. A high risk for late aortic-related death should be recognized in patients with BTAD.
A reduced Landau-de Gennes study for nematic equilibria in three-dimensional prisms
Authors: Han Yucen , Shi Baoming , Zhang Lei , Majumdar Apala
Published: November 2023

We model nematic liquid crystal configurations inside three-dimensional prisms, with a polygonal cross-section and Dirichlet boundary conditions on all prism surfaces. We work in a reduced Landau-de Gennes framework, and the Dirichlet conditions on the top and bottom surfaces are special in the sense that they are critical points of the reduced Landau-de Gennes energy on the polygonal cross-section. The choice of the boundary conditions allows us to make a direct correspondence between the three-dimensional Landau-de Gennes critical points and pathways on the two-dimensional Landau-de Gennes solution landscape on the polygonal cross-section. We explore this concept by means of asymptotic analysis and numerical examples, with emphasis on a cuboid and a hexagonal prism, focusing on three-dimensional multistability tailored by two-dimensional solution landscapes.
Whole-Genome Sequencing Predicting Phenotypic Antitubercular Drug Resistance: Meta-analysis
Authors: Tagami Yoichi , Horita Nobuyuki , Kaneko Megumi , Muraoka Suguru , Fukuda Nobuhiko , Izawa Ami , Kaneko Ayami , Somekawa Kohei , Kamimaki Chisato , Matsumoto Hiromi , Tanaka Katsushi , Murohashi Kota , Aoki Ayako , Fujii Hiroaki , Watanabe Keisuke , Hara Yu , Kobayashi Nobuaki , Kaneko Takeshi
Published: November 2023

Background

For simultaneous prediction of phenotypic drug susceptibility test (pDST) for multiple antituberculosis drugs, the whole genome sequencing (WGS) data can be analyzed using either a catalog-based approach, wherein 1 causative mutation suggests resistance, (eg, World Health Organization catalog) or noncatalog-based approach using complicated algorithm (eg, TB-profiler, machine learning). The aim was to estimate the predictive ability of WGS-based tests with pDST as the reference, and to compare the 2 approaches.

Methods

Following a systematic literature search, the diagnostic test accuracies for 14 drugs were pooled using a random-effect bivariate model.

Results

Of 779 articles, 44 with 16 821 specimens for meta-analysis and 13 not for meta-analysis were included. The areas under summary receiver operating characteristic curve suggested test accuracy was excellent (0.97–1.00) for 2 drugs (isoniazid 0.975, rifampicin 0.975), very good (0.93–0.97) for 8 drugs (pyrazinamide 0.946, streptomycin 0.952, amikacin 0.968, kanamycin 0.963, capreomycin 0.965, para-aminosalicylic acid 0.959, levofloxacin 0.960, ofloxacin 0.958), and good (0.75–0.93) for 4 drugs (ethambutol 0.926, moxifloxacin 0.896, ethionamide 0.878, prothionamide 0.908). The noncatalog-based and catalog-based approaches had similar ability for all drugs.

Conclusions

WGS accurately identifies isoniazid and rifampicin resistance. For most drugs, positive WGS results reliably predict pDST positive. The 2 approaches had similar ability.

Clinical Trials Registration

UMIN-ID UMIN000049276.
Subclinical Atherosclerosis Across the Menopausal Transition in Women With and Without HIV
Authors: Peters Brandilyn A , Whalen Adam , Xue Xiaonan , Topper Elizabeth F , Weber Kathleen M , Tien Phyllis C , Kassaye Seble G , Minkoff Howard , Fox Ervin , Fischl Margaret A , Collins Lauren F , Floris-Moore Michelle , Hodis Howard N , Qi Qibin , Hanna David B , Sharma Anjali , Anastos Kathryn , Kaplan Robert C
Published: November 2023

The menopausal transition is a pivotal time of cardiovascular risk, but knowledge is limited in HIV. We studied longitudinal carotid artery intima-media thickness (CIMT) in the Women's Interagency HIV Study (2004–2019; 979 women/3247 person-visits; 72% with HIV). Among women with HIV only, those who transitioned had greater age-related CIMT progression compared to those remaining premenopausal (difference in slope = 1.64 µm/year, P = .002); and CIMT increased over time in the pretransition (3.47 µm/year, P = .002) and during the menopausal transition (9.41 µm/year, P < .0001), but not posttransition (2.9 µm/year, P = .19). In women with HIV, menopause may accelerate subclinical atherosclerosis as measured by CIMT.
Prior Sexually Transmitted Infections and HIV in Patients With Mpox, Chicago, Illinois (June 2022–March 2023)
Authors: Faherty Emily A G , Holly Taylor , Herrera Kara , Guidry Taylor , Lyang Jeffrey , Black Stephanie , Tabidze Irina
Published: November 2023

HIV is associated with severe mpox. Sexually transmitted infections (STIs) could facilitate mpox transmission. We estimated HIV and STI frequency among patients with mpox and compared characteristics associated with mpox severity. Mpox cases during 1 June 2022 to 31 March 2023 were matched to Illinois HIV/AIDS surveillance data. Among 1124 patients with mpox, 489 (44%) had HIV and 786 (70%) had prior or concurrent STI; 307 (39%) had ≥3 STI episodes. More patients with mpox who were living with HIV were hospitalized than those without HIV (10.3% vs 4.1%, P < .001). STI screening visits are opportunities to vaccinate against mpox and provide HIV prophylaxis or treatment.
Sarecycline pharmacokinetics/pharmacodynamics in the hollow-fibre model of Mycobacterium avium complex: so near and yet so far
Authors: Singh Sanjay , Boorgula Gunavanthi D , Aryal Santosh , Philley Julie V , Gumbo Tawanda , Srivastava Shashikant
Published: November 2023

Background

Poor sustained sputum culture conversion rates with the standard-of-care therapy highlight the need for better drugs to treat Mycobacterium avium complex pulmonary disease (MAC-PD).

Objective

To determine the pharmacokinetics/pharmacodynamics (PK/PD)-optimized exposure of sarecycline and its potential role in treating MAC-PD.

Methods

We performed MIC studies with MAC ATCC 700898 and 19 clinical isolates and test-tube static concentration–response studies. A dynamic hollow-fibre system model of intracellular MAC (HFS-MAC) study was performed mimicking six human-equivalent sarecycline dose concentration–time profiles to identify the PK/PD optimal exposure of sarecycline for MAC kill. The inhibitory sigmoid maximal effect (Emax) model was used for PK/PD analysis.

Results

The sarecycline MIC of MAC ATCC 700898 was 1 mg/L, while the MIC for the 19 clinical strains ranged between 32 and >256 mg/L. The concentration mediating 50% of Emax (EC50) was similar between intracellular and extracellular MAC. In the HFS-MAC, all six sarecycline doses killed intracellular MAC, with an Emax of 1.0 log10 cfu/mL below Day 0 burden (stasis). The sarecycline EC80 (optimal) exposure was identified as AUC0–24/MIC = 139.46.

Conclusions

Sarecycline demonstrated anti-MAC Emax in the HFS-MAC model better than ethambutol but worse than omadacycline (>5 log10 cfu/mL below stasis) in HFS-MAC. However, since currently approved highest oral sarecycline dose achieves an AUC0–24 of 48.2 mg·h/L and MAC MICs are >32 mg/L, the target AUC0–24/MIC of 139.46 is unlikely to be achieved in patients.
Involvement of cardiac glycosides targeting Na/K-ATPase in their inhibitory effects on c-Myc expression via its transcription, translation and proteasomal degradation
Authors: Tokugawa Muneshige , Inoue Yasumichi , Aoki Hiromasa , Miyajima Chiharu , Ishiuchi Kan'ichiro , Tsurumi Kento , Kujirai Chisane , Morishita Daisuke , Matsuno Michiyo , Mizukami Hajime , Ri Masaki , Iida Shinsuke , Makino Toshiaki , Aoyama Mineyoshi , Hayashi Hidetoshi
Published: November 2023

Cardiac glycosides (CGs) have been used for decades to treat heart failure and arrhythmic diseases. Recent non-clinical and epidemiological findings have suggested that CGs exhibit anti-tumor activities. Therefore, CGs may be repositioned as drugs for the treatment of cancer. A detailed understanding of the anti-cancer mechanisms of CGs is essential for their application to the treatment of targetable cancer types. To elucidate the factors associated with the anti-tumor effects of CGs, we performed transcriptome profiling on human multiple myeloma AMO1 cells treated with periplocin, one of the CGs. Periplocin significantly down-regulated the transcription of MYC (c-Myc), a well-established oncogene. Periplocin also suppressed c-Myc expression at the protein levels. This repression of c-Myc was also observed in several cell lines. To identify target proteins for the inhibition of c-Myc, we generated CG-resistant (C9) cells using a sustained treatment with digoxin. We confirmed that C9 cells acquired resistance to the inhibition of c-Myc expression and cell proliferation by CGs. Moreover, the sequencing of genomic DNA in C9 cells revealed the mutation of D128N in α1-Na/K-ATPase, indicating the target protein. These results suggest that CGs suppress c-Myc expression in cancer cells via α1-Na/K-ATPase, which provides further support for the anti-tumor activities of CGs.
An oscillating magnetic field suppresses ice-crystal growth during rapid freezing of muscle tissue of mice
Authors: Okuda Kana , Kaori Kunitani , Kawauchi Aiko , Miyu Ishii , Yomogida Kentaro
Published: November 2023

Regenerative medicine would benefit from a safe and efficient cryopreservation method to prevent the structural disruption caused by ice-crystal formation in cells and tissue. Various attempts have been made to overcome this problem, one of which is the use of an oscillating magnetic field (OMF). However, the underlying mechanism is unclear. In this study, to evaluate the effect of an OMF on ice-crystal formation in the leg muscles of mice, we used to use the frozen-section method with a slower freezing rate than is, usual which resulted in ice crystals forming in the tissue. We assessed the mean size and number per unit area of intracellular ice holes in sections of muscle tissue, with and without OMF. Ice-crystal growth was reduced in frozen tissue subjected to OMF. Furthermore, we evaluated the structure and function of proteins in frozen tissue subjected to OMF by immunostaining using an anti-dystrophin antibody and by enzymatic histochemistry for NADH-TR and myosin ATPase. The results imply that the ability of OMF to suppress ice-crystal growth might be related to their stabilization of bound water in biomolecules during freezing.
The story of social media: evolving news coverage of social media in American politics, 2006–2021
Authors: Lane Daniel S , Overbye-Thompson Hannah , Gagrčin Emilija
Published: November 2023

This article examines how American news media have framed social media as political technologies over time. To do so, we analyzed 16 years of political news stories focusing on social media, published by American newspapers (N = 8,218) and broadcasters (N = 6,064) (2006–2021). Using automated content analysis, we found that coverage of social media in political news stories: (a) increasingly uses anxious, angry, and moral language, (b) is consistently focused on national politicians (vs. non-elite actors), and (c) increasingly emphasizes normatively negative uses (e.g., misinformation) and their remedies (i.e., regulation). In discussing these findings, we consider the ways that these prominent normative representations of social media may shape (and limit) their role in political life.
Too scared to share? Fear of social sanctions for political expression on social media
Authors: Weeks Brian E , Halversen Audrey , Neubaum German
Published: November 2023

While social media provide opportunities for political expression, many people may be reluctant to share their opinions if they fear personal or professional repercussions for posting political views. Fear of social sanctions (FOSSs) therefore represents a promising approach to investigate why people often avoid expressing political opinions online. Using panel survey data collected during the 2020 U.S. election, this study examines the predictors of FOSSs, as well as its relationship with several forms of online political expression. Results indicate that the ideological diversity of people’s online networks fosters their FOSSs, which in turn is associated with decreases in several types of online political expression. Thus, FOSSs may be an important determinant in individuals’ calculations to express political opinions online and may also hinder lower commitment forms of political engagement.
Inulin prebiotic ameliorates type 1 diabetes dictating regulatory T cell homing via CCR4 to pancreatic islets and butyrogenic gut microbiota in murine model
Authors: Guimarães Jhefferson Barbosa , Rodrigues Vanessa Fernandes , Pereira Ítalo Sousa , Manso Gabriel Martins da Costa , Elias-Oliveira Jefferson , Leite Jefferson Antônio , Waldetario Mariana Camila Gonçalves Miranda , de Oliveira Sarah , Gomes Arilson Bernardo dos Santos Pereira , Faria Ana Maria Caetano , Ramos Simone Gusmão , Bonato Vânia L D , Silva João Santana , Vinolo Marco Aurélio Ramirez , Sampaio Ulliana Marques , Clerici Maria Teresa Pedrosa Silva , Carlos Daniela
Published: November 2023

Gut dysbiosis is linked to type 1 diabetes mellitus (T1D). Inulin (INU), a prebiotic, modulates the gut microbiota, promoting beneficial bacteria that produce essential short-chain fatty acids for immune regulation. However, how INU affects T1D remains uncertain. Using a streptozotocin-induced (STZ) mouse model, we studied INU's protective effects. Remarkably, STZ + INU mice resisted T1D, with none developing the disease. They had lower blood glucose, reduced pancreatic inflammation, and normalized serum insulin compared with STZ + SD mice. STZ + INU mice also had enhanced mucus production, abundant Bifidobacterium, Clostridium cluster IV, Akkermansia muciniphila, and increased fecal butyrate. In cecal lymph nodes, we observed fewer CD4+Foxp3+ regulatory T cells expressing CCR4 and more Foxp3+CCR4+ cells in pancreatic islets, with higher CCL17 expression. This phenotype was absent in CCR4-deficient mice on INU. INU supplementation effectively protects against experimental T1D by recruiting CCR4+ regulatory T cells via CCL17 into the pancreas and altering the butyrate-producing microbiota.
Contribution of smoking, disease history, and survival to lung cancer disparities in Black individuals
Authors: Skolnick Sarah , Cao Pianpian , Jeon Jihyoun , Meza Rafael
Published: November 2023

Background

Lung cancer is the leading cause of cancer deaths and disproportionately affects self-identified Black or African American (“Black”) people, especially considering their relatively low self-reported smoking intensity rates. This study aimed to determine the relative impact of smoking history and lung cancer incidence risk, histology, stage, and survival on these disparities.

Methods

We used 2 lung cancer models (MichiganLung-All Races and MichiganLung-Black) to understand why Black people have higher rates of lung cancer deaths. We studied how different factors, such as smoking behaviors, cancer development, histology, stage at diagnosis, and lung cancer survival, contribute to these differences.

Results

Adjusted for smoking history, approximately 90% of the difference in lung cancer deaths between the overall and Black populations (born in 1960) was the result of differences in the risk of getting lung cancer. Differences in the histology and stage of lung cancer and survival had a small impact (4% to 6% for each). Similar results were observed for the 1950 and 1970 birth cohorts, regardless of their differences in smoking patterns from the 1960 cohort.

Conclusions

After taking smoking into account, the higher rate of lung cancer deaths in Black people can mostly be explained by differences in the risk of developing lung cancer. As lung cancer treatments and detection improve, however, other factors may become more important in determining differences in lung cancer mortality between the Black and overall populations. To prevent current disparities from becoming worse, it is important to make sure that these improvements are available to everyone in an equitable way.
Self-Control in Pediatric Migraine Management: A Topical Review
Authors: Conour Cecily N , Sugiwaka Hiroko , Nelson Cecelia I , Duncan Christina L
Published: November 2023

Objective 

This review examines the role that two types of self-control may play in youth’s self-management of migraine. Although traditionally conceptualized from an inhibitory lens, self-control has both initiatory and inhibitory functions, and the authors suggest the distinction is important in relation to youth’s ability to adhere to different components of migraine treatment regimens.

Methods 

A topical review of the literature was conducted to identify evidence-based interventions to treat pediatric migraine and conceptualize the role self-control (both initiatory and inhibitory) may play in adherence to its regimen. Both PsycInfo and PubMed databases were used to identify relevant articles.

Results 

Existing evidence-based interventions and recommendations for pediatric migraine require inhibitory self-control (e.g., avoiding caffeine, tobacco) and initiatory self-control (e.g., taking medication). Formal intervention programs (e.g., cognitive behavioral therapy) tend to employ initiatory self-control (e.g., modifying physical reactions in response to biofeedback).

Conclusions 

Understanding the distinct types of self-control required for adherence to different interventions allows for a better conceptualization of self-management of pediatric migraine. Individuals may struggle with adherence when they have deficits in one or both types of self-control skills. Future research should consider whether self-control is associated with differential adherence patterns in pediatric migraine management.
Bayesian profile regression for clustering analysis involving a longitudinal response and explanatory variables
Authors: Rouanet Anaïs , Johnson Rob , Strauss Magdalena , Richardson Sylvia , Tom Brian D , White Simon R , Kirk Paul D W
Published: November 2023

The identification of sets of co-regulated genes that share a common function is a key question of modern genomics. Bayesian profile regression is a semi-supervised mixture modelling approach that makes use of a response to guide inference toward relevant clusterings. Previous applications of profile regression have considered univariate continuous, categorical, and count outcomes. In this work, we extend Bayesian profile regression to cases where the outcome is longitudinal (or multivariate continuous) and provide PReMiuMlongi, an updated version of PReMiuM, the R package for profile regression. We consider multivariate normal and Gaussian process regression response models and provide proof of principle applications to four simulation studies. The model is applied on budding-yeast data to identify groups of genes co-regulated during the Saccharomyces cerevisiae cell cycle. We identify four distinct groups of genes associated with specific patterns of gene expression trajectories, along with the bound transcriptional factors, likely involved in their co-regulation process.