bluuebunny/crossref_metadata_2025 huggingface dataset:
Carney complex predisposes to breast cancer: prospective study of 50 women
Authors: Vaduva Patricia , Violon Florian , Jouinot Anne , Bouys Lucas , Espiard Stéphanie , Bonnet-Serrano Fidéline , North Marie Odile , Cardot-Bauters Catherine , Raverot Gerald , Hieronimus Sylvie , Lefebvre Hervé , Nunes Marie-Laure , Tabarin Antoine , Groussin Lionel , Assié Guillaume , Sibony Mathilde , Vantyghem Marie-Christine , Pasmant Eric , Bertherat Jérôme
Published: January 2024

Objective

Carney complex (CNC) is a rare genetic syndrome, mostly due to germline loss-of-function pathogenic variants in PRKAR1A. Carney complex includes pigmented skin lesions, cardiac myxomas, primary pigmented nodular adrenocortical dysplasia, and various breast benign tumors.

Design

The present study was designed to describe the characteristics of breast lesions in CNC patients and their association with other manifestations of CNC and PRKAR1A genotype.

Methods

A 3-year follow-up multicenter French prospective study of CNC patients included 50 women who were analyzed for CNC manifestations and particularly breast lesions, with breast imaging, genotyping, and hormonal settings.

Results

Among the 38 women with breast imaging, 14 (39%) had breast lesions, half of them bilateral. Ten women (26%) presented with benign lesions and six with breast carcinomas (16%): one had ductal carcinoma in situ at 54, and five had invasive cancer before 50 years old, whom one with contralateral breast cancer during follow-up. The occurrence of breast cancer was more frequent in women with PRKAR1A pathogenic variant odds ratio = 6.34 (1.63-17.91) than in general population of same age. The mean age at breast cancer diagnosis was 44.7 years old: 17 years younger than in the general population. Breast cancer patients had good prognosis factors. All breast carcinomas occurred in individuals with familial CNC and PRKAR1A pathogenic variants. Loss of heterozygosity at the PRKAR1A locus in the 2 invasive breast carcinomas analyzed suggested a driver role of this tumor suppressor gene.

Conclusions

As CNC could predispose to breast carcinoma, an adequate screening strategy and follow-up should be discussed in affected women.

Clinical Trial Registration

ClinicalTrial.gov NCT00668291.
The evolution of multi-component weapons in the superfamily of leaf-footed bugs
Authors: Miller Christine W , Kimball Rebecca T , Forthman Michael
Published: January 2024

Sexually selected weapons, such as the antlers of deer, claws of crabs, and tusks of beaked whales, are strikingly diverse across taxa and even within groups of closely related species. Phylogenetic comparative studies have typically taken a simplified approach to investigate the evolution of weapon diversity, examining the gains and losses of entire weapons, major shifts in size or type, or changes in location. Less understood is how individual weapon components evolve and assemble into a complete weapon. We addressed this question by examining weapon evolution in the diverse, multi-component hind-leg and body weapons of leaf-footed bugs, superfamily Coreoidea (Hemiptera: Heteroptera). Male leaf-footed bugs use their morphological weapons to fight for access to mating territories. We used a large multilocus dataset comprised of ultraconserved element loci for 248 species and inferred evolutionary transitions among component states using ancestral state estimation. Our results suggest that weapons added components over time with some evidence of a cyclical evolutionary pattern—gains of components followed by losses and then gains again. Furthermore, our best estimate indicated that certain trait combinations evolved repeatedly across the phylogeny, suggesting that they function together in battle or that they are genetically correlated. This work reveals the remarkable and dynamic evolution of weapon form in the leaf-footed bugs and provides insights into weapon assembly and disassembly over evolutionary time.
Improving compliance with personal protective equipment among anaesthetists through behaviour-changing interventions during the coronavirus disease 2019(COVID-19) pandemic
Authors: Chia Pamela , Tang Leonard , Tse Gerald , How Molly , Wong Loong Tat , Mok May , Chong Shin Yuet
Published: January 2024

Since 2020, the coronavirus disease 2019 (COVID-19) pandemic has seen many changes in our daily infection prevention behaviours so as to reduce healthcare-associated transmission of COVID-19 in patients and healthcare workers. In the early phases of the COVID-19 pandemic of 2020, there was much emphasis on compliant personal protective equipment utilization in the operating theatres (OTs) for COVID-19-positive patients. However, during this period, there was a lack of international validated protocols on the appropriate handling and subsequent storage of personal protective equipment in the context of aerosol-generating procedures in OTs for asymptomatic antigen rapid test (ART)-negative patients. Given the potential for transmission even with a negative ART due to the incubation period, our team developed a checklist of eye protection (e.g. goggles/face shield) and N95 mask handling and storage in non-isolation OTs for these patients. We sought to improve the compliance of best practices from 20% to 80% amongst junior anaesthetists in Singapore General Hospital so as to prevent infection transmission and cross-contamination in the OT through education and behaviour-changing interventions. This quality improvement project took place over 19 weeks from June to October 2020 by our team of anaesthetists and nurse clinicians in the non-isolation OT setting. To analyse the problem, we performed a root cause analysis to understand attitudes and beliefs driving their behaviour. The top 80% of cited root causes for non-compliance then guided prioritization of resources for subsequent behaviour-changing interventions. Using the comprehensive infection control checklist, we conducted several plan-do-study-act cycles while implementing this new checklist amongst junior anaesthetists. A total of 227 assessments of junior anaesthetists were made in the care of asymptomatic ART-negative patients. Compliance with correctly handling goggles post-intubation started out as 33.3% in Week 1, which improved to 78.5% by Week 19. Compliance with goggle storage and face shield disposal started out at 13.6% in Week 1 and increased to 78.6% by Week 19. We attributed this improvement to education and behaviour-changing interventions. This quality improvement project focusing on improving compliance with personal protective equipment utilization during the COVID-19 pandemic in the management of asymptomatic ART-negative patients in non-isolation OTs demonstrated the importance of interventions of education, persuasion, modelling, and training in effecting and sustaining organizational behaviour change in physicians and other healthcare personnel.
Genetic mixing and demixing on expanding spherical frontiers
Authors: García Vázquez Alba , Mitarai Namiko , Jauffred Liselotte
Published: January 2024

Genetic fluctuation during range expansion is a key process driving evolution. When a bacterial population is expanding on a 2D surface, random fluctuations in the growth of the pioneers at the front line cause a strong demixing of genotypes. Even when there is no selective advantage, sectors of low genetic diversity are formed. Experimental studies of range expansions in surface-attached colonies of fluorescently labelled micro-organisms have contributed significantly to our understanding of fundamental evolutionary dynamics. However, experimental studies on genetic fluctuations in 3D range expansions have been sparse, despite their importance for tumour or biofilm development. We encapsulated populations of two fluorescent Escherichia coli strains in inoculation droplets (volumes $\sim 0.1$ nl). The confined ensemble of cells grew when embedded in a hydrogel—with nutrients—and developed 3D colonies with well-defined, sector-like regions. Using confocal laser scanning microscopy, we imaged the development of 3D colonies and the emergence of sectors. We characterized how cell concentration in the inoculation droplet controls sectors, growth rate, and the transition from branched colonies to quasi-spherical colonies. We further analysed how sectors on the surface change over time. We complement these experimental results with a modified 3D Eden growth model. The model in 3D spherical growth predicts a phase, where sectors are merging, followed by a steady increase (constant rate), and the experimentally analysed sectors were consistent with this prediction. Therefore, our results demonstrate qualitative differences between radial (2D) and spherical (3D) range expansions and their importance in gene fixation processes.
Glycoproteomic profile of human tissue-nonspecific alkaline phosphatase expressed in osteoblasts
Authors: Atanasova Diana , Mirgorodskaya Ekaterina , Moparthi Lavanya , Koch Stefan , Haarhaus Mathias , Narisawa Sonoko , Millán José Luis , Landberg Eva , Magnusson Per
Published: January 2024

Tissue-nonspecific alkaline phosphatase (TNALP) is a glycoprotein expressed by osteoblasts that promotes bone mineralization. TNALP catalyzes the hydrolysis of the mineralization inhibitor inorganic pyrophosphate and ATP to provide inorganic phosphate, thus controlling the inorganic pyrophosphate/inorganic phosphate ratio to enable the growth of hydroxyapatite crystals. N-linked glycosylation of TNALP is essential for protein stability and enzymatic activity and is responsible for the presence of different bone isoforms of TNALP associated with functional and clinical differences. The site-specific glycosylation profiles of TNALP are, however, elusive. TNALP has 5 potential N-glycosylation sites located at the asparagine (N) residues 140, 230, 271, 303, and 430. The objective of this study was to reveal the presence and structure of site-specific glycosylation in TNALP expressed in osteoblasts. Calvarial osteoblasts derived from Alpl+/− expressing SV40 Large T antigen were transfected with soluble epitope-tagged human TNALP. Purified TNALP was analyzed with a lectin microarray, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and liquid chromatography with tandem mass spectrometry. The results showed that all sites (n = 5) were fully occupied predominantly with complex-type N-glycans. High abundance of galactosylated biantennary N-glycans with various degrees of sialylation was observed on all sites, as well as glycans with no terminal galactose and sialic acid. Furthermore, all sites had core fucosylation except site N271. Modelling of TNALP, with the protein structure prediction software ColabFold, showed possible steric hindrance by the adjacent side chain of W270, which could explain the absence of core fucosylation at N271. These novel findings provide evidence for N-linked glycosylation on all 5 sites of TNALP, as well as core fucosylation on 4 out of 5 sites. We anticipate that this new knowledge can aid in the development of functional and clinical assays specific for the TNALP bone isoforms.
Flipping the paradigm of weak patent rights: from theories to evidence
Authors: Maronero Cecilia , Bichlmayr Annika
Published: January 2024

In recent years, we have been confronted with complex challenges requiring coordinated global responses, such as the Covid-19 pandemic and climate change. At the same time, a negative sentiment towards IP rights (IPRs)—and patents in particular—has gained momentum. Sceptics claim that patents hinder the technology adoption needed to tackle these global crises, and proposals to weaken patent rights have intensified. A closer examination of these efforts reveals that they are generally expressed in two ways: on one side, anti-patent advocacy is backed up by popular, although empirically shaky, theories aimed at questioning patents’ effectiveness; on the other, the paradigm of weak patents is put forward through more incremental and—only at first glance—subtle policy changes that can potentially undermine the foundations of a balanced patent system. We address and review both efforts. Firstly, we examine the ‘first-mover advantage’ theory and we find it inadequate as a substitute for patent protection. Secondly, we focus on the cellular connectivity sector where efforts to weaken the patent system are intense. We discuss three common policy proposals: (i) royalty-free licensing for standard essential patents (SEPs), (ii) limiting injunctive relief under the proportionality principle and (iii) narrowing patent transfers and technology markets. We demonstrate that these seemingly minor changes can destabilize the patent system, and we explore the importance of a balanced licensing framework for the emergent Internet of Things (IoT). Ultimately, we highlight how a strong, efficient and balanced patent system remains crucial for fostering research and development (R&D), incentivizing innovators and effectively addressing the global challenges of our current times.
Lower pretreatment serum testosterone level predicts poor prognosis in the patients with metastatic hormone-sensitive prostate cancer undergoing androgen deprivation therapy
Authors: Yoshida Takahiro , Kawai Taketo , Hagiwara Kanade , Yanagida Kazuki , Noda Michio , Tokura Yuumi , Yoshimura Itsuki , Kaneko Tomoyuki , Nakagawa Tohru
Published: January 2024

Objective

This study aimed to reveal the association between pretreatment serum testosterone levels and prognosis in patients with metastatic hormone-sensitive prostate cancer treated with androgen deprivation therapy.

Methods

A total of 91 patients were included in this retrospective study. Clinical data were obtained through chart review. Multivariate cox proportional hazards analyses addressed the impact of variables on castration-resistant prostate cancer-free and overall survivals.

Results

During a median follow-up of 41.7 months, 61 (67%) and 49 (54%) patients developed castration-resistant prostate cancer and died, respectively. The median castration-resistant prostate cancer-free and overall survivals were 15.5 and 59.9 months, respectively. The cutoff value for discriminating between low- and high-testosterone levels was determined as 450 ng/dl by calculating the receiver operating characteristic curve. Patients in the low-testosterone group (n = 37) had a significantly higher body mass index, worse comorbidities represented by the higher Charlson comorbidity index and higher serum lactate dehydrogenase levels, than those in the high-testosterone group (n = 54). Castration-resistant prostate cancer free and overall survivals were significantly shorter in the low-testosterone group than in the high-testosterone group (P = 0.021 and P < 0.001, respectively). Multivariate analysis identified testosterone level of <450 ng/dl as an independent factor predicting development of castration-resistant prostate cancer (hazard ratio 2.28, P = 0.007), along with high-volume disease and Gleason score 9–10. Similarly, testosterone level of <450 ng/dl was independently associated with shorter overall survival (hazard ratio 2.84, P = 0.006), along with higher Charlson comorbidity index, visceral metastasis and higher alkaline phosphatase level.

Conclusions

Lower baseline serum testosterone levels predict poor prognosis in patients with metastatic hormone-sensitive prostate cancer.
Transient receptor potential cation channel subfamily V member 1 (TRPV1) targeted PET imaging
Authors: Tateishi Ukihide , Doi Hisashi
Published: January 2024

Transient receptor potential cation channel subfamily V member 1 (TRPV1) was identified using capsaicin, a pungent compound that is present in red pepper. The activation of TRPV1 induces an influx of calcium ions into cells and causes excitation of sensory neurons, associating with thermal sensing, sweating and pain. TRPV1 is also identified in various types of cancer cells. The expression of TRPV1 in cancer cells depends on the type of cancer and the stage of the disease. Therefore, TRPV1 has been considered a potential target of medicinal chemistry for drug development, and blocking its activation may lead to cancer therapy and pain relief. However, the details of the pathophysiological function of TRPV1 in vivo are still unclear. To explore practical use of TRPV1, we focused on positron emission tomography imaging and developed a 11C-radiolabeled tracer to visualize TRPV1.
Efficacy of radiation therapy in Japanese patients with positive margins after breast-conserving surgery
Authors: Uomori Toshitaka , Horimoto Yoshiya , Ueki Yuko , Ishizuka Yumiko , Onagi Hiroko , Hayashi Takuo , Watanabe Junichiro , Shikama Naoto
Published: January 2024

Background

Additional surgical resection is recommended after breast-conserving surgery if the surgical margin is pathologically positive. However, in clinical practice, radiation therapy is sometimes used instead for several reasons. Irradiation may be appropriate for some patients, but real-world data is still insufficient to establish it as standard treatment. We retrospectively investigated the status of local control in patients who received irradiation for positive margins.

Methods

We investigated 85 patients with positive margins after curative partial mastectomy who were treated with irradiation instead of additional excision during the period 2006–2013. The patients received whole-breast irradiation (43.2–50 Gy) using photon beams and additional tumour-bed boost (8.1–16 Gy) using electron beams. Intrabreast tumour recurrence was defined as secondary cancer within the ipsilateral conserved breast. Surgical margin was defined as positive if tumour cell exposure was pathologically confirmed on the margin.

Results

Seven patients (8.2%) developed intrabreast tumour recurrence during a mean observation period of 119 months. As to components of positive margin, 76 cases were positive for an intraductal component, of which seven (9.2%) developed intrabreast tumour recurrence. Meanwhile, all nine cases positive for an invasive component were free from intrabreast tumour recurrence. Two of the intrabreast tumour recurrence cases seemed to develop new lesions rather than recurrence, considering tumour location. The cumulative incidence of intrabreast tumour recurrence over 10 years was 6.1%. Limited to true recurrence, intrabreast tumour recurrence incidence was 4.9%.

Conclusion

Our real-world data supports irradiation as an alternative to additional surgical intervention for positive margins after breast-conserving surgery and offers a basis for further research.
Viral presence and immunopathology in a kidney transplant recipient with fatal COVID-19: a clinical autopsy report
Authors: van Eijk Larissa E , Bourgonje Arno R , Mastik Mirjam F , Snippe Dirk , Bulthuis Marian L C , Vos Wim , Bugiani Marianna , Smit Jolanda M , Berger Stefan P , van der Voort Peter H J , van Goor Harry , den Dunnen Wilfred F A , Hillebrands Jan-Luuk
Published: January 2024

COVID-19 is of special concern to immunocompromised individuals, including organ transplant recipients. However, the exact implications of COVID-19 for the immunocompromised host remain unclear. Existing theories regarding this matter are controversial and mainly based on clinical observations. Here, the postmortem histopathology, immunopathology, and viral presence in various tissues of a kidney transplant recipient with COVID-19 were compared to those of 2 nontransplanted patients with COVID-19 matched for age, sex, length of intensive care unit stay, and admission period in the pandemic. None of the tissues of the kidney transplant recipient demonstrated the presence of SARS-CoV-2. In lung tissues of both controls, some samples showed viral positivity with high Ct values with quantitative reverse transcription polymerase chain reaction. The lungs of the kidney transplant recipient and controls demonstrated similar pathology, consisting of acute fibrinous and organizing pneumonia with thrombosis and an inflammatory response with T cells, B cells, and macrophages. The kidney allograft and control kidneys showed a similar pattern of interstitial lymphoplasmacytic infiltration. No myocarditis could be observed in the hearts of the kidney transplant recipient and controls, although all cases contained scattered lymphoplasmacytic infiltrates in the myocardium, pericardium, and atria. The brainstems of the kidney transplant recipient and controls showed a similar pattern of lymphocytic inflammation with microgliosis. This research report highlights the possibility that, based on the results obtained from this single case, at time of death, the immune response in kidney transplant recipients with long-term antirejection immunosuppression use prior to severe illness is similar to nontransplanted deceased COVID-19 patients.
Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study)
Authors: Schüz Joachim , Kovalevskiy Evgeny , Olsson Ann , Moissonnier Monika , Ostroumova Evgenia , Ferro Gilles , Feletto Eleonora , Schonfeld Sara J , Byrnes Graham , Tskhomariia Iraklii , Straif Kurt , Morozova Tatiana , Kromhout Hans , Bukhtiyarov Igor
Published: January 2024

Background

We investigated mortality in workers of the world’s largest chrysotile mine and enrichment factories located in the town of Asbest, Russian Federation.

Methods

This historical cohort study included all workers employed for at least 1 year between 1975 and 2010 and follow-up until the end of 2015. Cumulative exposure to dust was estimated based on workers’ complete occupational history linked to dust measurements systematically collected from the 1950s. Exposure to chrysotile fibers was estimated using dust-to-fiber conversion factors. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated as mortality rate ratios in Poisson regression models.

Results

A total of 30 445 (32% women) workers accumulated 721 312 person-years at risk and 11 110 (36%) died. Of the workers, 54% had more than 30 years since their first exposure. We found an exposure-response between cumulative dust and lung cancer mortality in men. No clear association with dust exposure but a modest increase in the highest category of fiber exposure was seen for lung cancer in women. Mesothelioma mortality was increased (RR = 7.64, 95% CI = 1.18 to 49.5, to at least 80 fibers per cm3 years and RR = 4.56, 95% CI = 0.94 to 22.1, to at least 150 mg/m3 years [dust]), based on 13 deaths. For colorectal and stomach cancer, there were inconsistent associations. No associations were seen for laryngeal or ovarian cancer.

Conclusion

In this large-scale epidemiological study in the world’s largest active asbestos mine, we confirmed an increased risk of mesothelioma with high fiber exposure and an increasing mortality for lung cancer in men with increasing dust exposure. Less clear-cut increased lung cancer mortality was seen in the women. Continued mortality follow-up is warranted.
Critical mass condition of majority bureaucratic behavioral change in representative bureaucracy: a theoretical clarification and a nonparametric exploration
Authors: Li Danyao
Published: January 2024

Representative bureaucracy theory examines how bureaucrats’ demographics impact outcomes for clients with shared identities, with “critical mass” posited as an enabling condition. Yet empirical evidence is mixed regarding where this threshold stands. To reconcile these inconsistencies, this study emphasizes the need to first clarify the mechanisms that underpin critical mass requirements. Specifically, I attend to how majority behavior changes due to enhanced representation and evaluate corresponding critical mass condition. Nonparametric analyses of traffic stop data in two states find that, in Washington, the critical mass where White officers show reduced bias towards Black drivers occurs when Black officers constitute 6–9 percent of the force. In South Carolina, similar shifts occur at 9–11 and 19–23 percent Black representation. While findings indicate improved policing towards Black drivers, increased representation still falls short of achieving full parity between Black and White drivers. No significant critical mass is observed for Hispanic representation in either state.
Religious influence and its protection
Authors: Lewin David
Published: January 2024

John Tillson’s book Children, Religion and the Ethics of Influence addresses several themes: the ground and nature of ethical responsibility; the means and goals of ethical formative influence; the nature and ground of religious belief. In this article, I focus on the issue of justification for educational influence in general. Attention to this issue could avoid some intractable problems of specifically religious influence, most particularly the challenge of providing satisfactory criteria for what belongs to the category of religion. Whilst there may be important reasons for examining specifically religious influence, I argue that religious influence is not fundamentally different from other forms of influence, and that the logic of the ethics of influence in general would encompass the logic of religious influence. If the educator is to justify certain forms of influence, then they should employ a kind of restraint: the educator should influence whilst simultaneously protect the influencee from that very influence.
Gradient synchronization for multivariate functional data, with application to brain connectivity
Authors: Chen Yaqing , Lin Shu-Chin , Zhou Yang , Carmichael Owen , Müller Hans-Georg , Wang Jane-Ling
Published: January 2024

Quantifying the association between components of multivariate random curves is of general interest and is a ubiquitous and basic problem that can be addressed with functional data analysis. An important application is the problem of assessing functional connectivity based on functional magnetic resonance imaging (fMRI), where one aims to determine the similarity of fMRI time courses that are recorded on anatomically separated brain regions. In the functional brain connectivity literature, the static temporal Pearson correlation has been the prevailing measure for functional connectivity. However, recent research has revealed temporally changing patterns of functional connectivity, leading to the study of dynamic functional connectivity. This motivates new similarity measures for pairs of random curves that reflect the dynamic features of functional similarity. Specifically, we introduce gradient synchronization measures in a general setting. These similarity measures are based on the concordance and discordance of the gradients between paired smooth random functions. Asymptotic normality of the proposed estimates is obtained under regularity conditions. We illustrate the proposed synchronization measures via simulations and an application to resting-state fMRI signals from the Alzheimer’s Disease Neuroimaging Initiative and they are found to improve discrimination between subjects with different disease status.
What We Know About Homeless Veterans With Other-than-honorable and Punitive Discharges: Data From the Grant and Per Diem (GPD) Program
Authors: Jutkowitz Eric , McCreedy Ellen , Halladay Christopher , Tsai Jack
Published: January 2024

Introduction

The U.S. DVA Grant and Per Diem (GPD) program funds community agencies to provide housing and case management services to Veterans experiencing homelessness. GPD is one of the few VA programs that can enroll Veterans with Other-than-Honorable (OTH) military discharges. The characteristics of OTH Veterans and their outcomes in GPD are unknown.

Materials and Methods

We linked the Homeless Operations and Management Evaluation System database and VA Corporate Data Warehouse to identify Veterans with complete GPD enrollment and discharge data between 2018 and 2020. We categorized Veterans into three military discharge groups: Honorable, OTH, or Punitive. We evaluated key GPD process and outcomes measures: days enrolled in GPD, use of VA-funded emergency department care while in GPD, and whether a Veteran was successfully discharged from GPD, their housing status at program exit, employment status at program exit, and connection to mental health and substance abuse treatment at discharge. We conducted multivariable regressions to determine the adjusted association (controlling for demographics and comorbidities) between military discharge status and process and outcome measures.

Results

Among 21,646 Veterans in the GPD program, 20,517 (95%) were honorably discharged; 811 (4%) had an OTH discharge; and 318 (1%) had a Punitive discharge. There was no difference in GPD length of enrollment by discharge status. Compared to honorably discharged veterans, OTH and Punitive discharged Veterans were less likely to successfully exit GPD, more likely to be homeless and employed at program exit, and were less likely to have a VA-funded emergency department visit while in GPD and less likely to be connected to mental health care or substance use treatment at program exit.

Conclusions

The GPD program serves hundreds of homeless Veterans with OTH and Punitive discharges every year, but they seem to be at greater risk for negative health and psychosocial outcomes and do not have the same access to VA services as other Veterans. These findings may inform policy considerations about expanding VA care and opportunities for community providers to serve Veterans with OTH and Punitive discharges.
Simultaneous observations of a breakout current sheet and a flare current sheet in a coronal jet event
Authors: Yang Liheng , Yan Xiaoli , Xue Zhike , Xu Zhe , Zhang Qingmin , Hou Yijun , Wang Jincheng , Chen Huadong , Li Qiaoling
Published: January 2024

Previous studies have revealed that solar coronal jets triggered by the eruption of minifilaments (MFs) conform to the famous magnetic-breakout mechanism. In such a scenario, a breakout current sheet (BCS) and a flare current sheet (FCS) should be observed during the jets. With high spatial and temporal resolution data from the SDO, the NVST, the RHESSI, the Wind, and the GOES, we present observational evidence of a BCS and a FCS formation during coronal jets driven by a MF eruption occurring in the active region NOAA 11726 on 2013 April 21. Magnetic field extrapolation shows that the MF was enclosed by a fan-spine magnetic structure. The MF was activated by flux cancellation under it, and then slowly rose. A BCS formed when the magnetic fields wrapping the MF squeezed to antidirectional external open fields. Simultaneously, one thin bright jet and two bidirectional jet-like structures were observed. As the MF erupted as a blowout jet, a FCS was formed when the two distended legs inside the MF field came together. One end of the FCS connected the post-flare loops. The BCS’s peak temperature was calculated to be 2.5 MK. The FCS’s length, width, and peak temperature were calculated to be 4.35–4.93, 1.31–1.45, and 2.5 MK, respectively. The magnetic reconnection rate associated with the FCS was estimated to be from 0.266 to 0.333. This event is also related to a type III radio burst, indicating its influence on interplanetary space. These observations support the scenario of the breakout model as the trigger mechanism of coronal jets, and flux cancellation was the driver of this event.
Reassessing the efficacy of bevacizumab in newly diagnosed glioblastoma: A systematic review and external pseudodata-based analysis
Authors: Sferruzza Giacomo , Malcangi Massimo , Bosco Luca , Finocchiaro Gaetano
Published: January 2024

Background

First-line use of bevacizumab for glioblastoma (GBM) was evaluated in 2 phase 3 randomized controlled trials (RCT), demonstrating an impact on progression-free survival but not overall survival (OS). However, the crossover events of these trials raised concerns regarding the reliability of this latter analysis. In this study, we conducted an external control-based reassessment of the bevacizumab efficacy in newly diagnosed GBM (ndGBM) against the standard Stupp protocol.

Methods

A systematic review of the literature was conducted to identify the phase 3 RCTs in ndGBM incorporating the Stupp protocol as an arm. For the selected studies, we extracted individual patient survival pseudodata of the Stupp protocol arm by digitizing the Kaplan–Meier plots. A comprehensive pipeline was established to select suitable control studies as external benchmarks.

Results

Among the 13 identified studies identified in our systematic review, 4 studies resulted as comparable with the AVAglio trial and 2 with the RTOG 0825. Pooled individual patient pseudodata analysis showed no differences in terms of OS when bevacizumab was added to the Stupp protocol.

Conclusions

The external-controlled-based reassessment of the bevacizumab treatment in ndGBM confirmed its lack of efficacy in extending OS. Our study includes a summary table of individual patient survival pseudodata from all phase 3 RCTs in ndGBM employing the Stupp protocol and provides a pipeline that offers comprehensive guidance for conducting external control-based assessments in ndGBM.
Association of Tecovirimat Therapy With Mpox Symptom Improvement: A Cross-sectional Study—King County, Washington, May–October 2022
Authors: Karmarkar Ellora N , Golden Matthew R , Kerani Roxanne P , Pogosjans Sargis , Chow Eric J , Bender Ignacio Rachel A , Ramchandani Meena S , Kay Meagan K , Cannon Chase A , Dombrowski Julia C
Published: January 2024

Background

Data on tecovirimat effectiveness for human mpox are limited. We conducted a retrospective cross-sectional interview-based study to identify associations between tecovirimat treatment and the mpox clinical course.

Methods

Using public health surveillance data from King County, Washington, we recruited and interviewed persons diagnosed with mpox during May–October 2022. We calculated descriptive statistics on demographics, vaccination status, comorbidities, and symptoms including 3 self-reported dates (symptom onset, first date of symptom improvement, and illness resolution). We used multivariable linear regression, stratified by illness severity, to evaluate the association of tecovirimat treatment with time to symptom improvement and time to illness resolution. We compared individuals who did not receive tecovirimat to participants who started tecovirimat early (≤5 days from symptom onset) and late (>5 days and ≤28 days from symptom onset) in their illness.

Results

Of 465 individuals diagnosed with mpox, 115 (25%) participated in this study. Eighty participants (70%) received tecovirimat and 43 (37%) initiated tecovirimat early. Sixty-eight (59%) reported severe symptoms during their illness, including proctitis (n = 38 [33%]), rectal bleeding (n = 27 [24%]), or severe pain (n = 24 [21%]). In the multivariable analysis, early tecovirimat was associated with shorter time to symptom improvement (−5.5 days, P = .04) among participants with severe illness but not among those with nonsevere illness (0.9 day, P = .66). Early tecovirimat was not associated with faster illness resolution, regardless of severity.

Conclusions

Our small study suggests that early tecovirimat initiation may hasten subjective symptomatic improvement in people with severe mpox. Larger randomized trials are needed to evaluate this finding.
Incidence and Predictors of Tuberculosis-associated IRIS in People With HIV Treated for Tuberculosis: Findings From Reflate TB2 Randomized Trial
Authors: Coelho Lara E , Chazallon Corine , Laureillard Didier , Escada Rodrigo , N’takpe Jean-Baptiste , Timana Isabelle , Messou Eugène , Eholie Serge , Khosa Celso , Chau Giang D , Cardoso Sandra Wagner , Veloso Valdiléa G , Delaugerre Constance , Molina Jean-Michel , Grinsztejn Beatriz , Marcy Olivier , De Castro Nathalie
Published: January 2024

Background

After antiretroviral therapy (ART) initiation, people with HIV (PWH) treated for tuberculosis (TB) may develop TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Integrase inhibitors, by providing a faster HIV-RNA decline than efavirenz, might increase the risk for this complication. We sought to assess incidence and determinants of TB-IRIS in PWH with TB on raltegravir- or efavirenz-based ART.

Methods

We conducted a secondary analysis of the Reflate TB 2 trial, which randomized ART-naive PWH on standard TB treatment, to receive raltegravir- or efavirenz-based ART. The primary objective was to evaluate the incidence of TB-IRIS. Incidence rate ratio comparing TB-IRIS incidence in each arm was calculated. Kaplan-Meier curves were used to compare TB-IRIS–free survival probabilities by ART arm. Cox regression models were fitted to analyze baseline characteristics associated with TB-IRIS.

Results

Of 460 trial participants, 453 from Brazil, Côte d’Ivoire, Mozambique, and Vietnam were included in this analysis. Baseline characteristics were median age 35 years (interquartile range [IQR], 29–43), 40% female, 69% pulmonary TB only, median CD4, 102 (IQR, 38–239) cells/mm³, and median HIV RNA, 5.5 (IQR, 5.0–5.8) log copies/mL. Forty-eight participants developed TB-IRIS (incidence rate, 24.7/100 PY), 19 cases in the raltegravir arm and 29 in the efavirenz arm (incidence rate ratio 0.62, 95% confidence interval .35–1.10). Factors associated with TB-IRIS were: CD4 ≤ 100 cells/μL, HIV RNA ≥500 000 copies/mL, and extrapulmonary/disseminated TB.

Conclusions

We did not demonstrate that raltegravir-based ART increased the incidence of TB-IRIS compared with efavirenz-based ART. Low CD4 counts, high HIV RNA, and extrapulmonary/disseminated TB at ART initiation were associated with TB-IRIS.
Collective privacy recovery: Data-sharing coordination via decentralized artificial intelligence
Authors: Pournaras Evangelos , Ballandies Mark Christopher , Bennati Stefano , Chen Chien-fei
Published: January 2024

Collective privacy loss becomes a colossal problem, an emergency for personal freedoms and democracy. But, are we prepared to handle personal data as scarce resource and collectively share data under the doctrine: as little as possible, as much as necessary? We hypothesize a significant privacy recovery if a population of individuals, the data collective, coordinates to share minimum data for running online services with the required quality. Here, we show how to automate and scale-up complex collective arrangements for privacy recovery using decentralized artificial intelligence. For this, we compare for the first time attitudinal, intrinsic, rewarded, and coordinated data sharing in a rigorous living-lab experiment of high realism involving >27,000 real data disclosures. Using causal inference and cluster analysis, we differentiate criteria predicting privacy and five key data-sharing behaviors. Strikingly, data-sharing coordination proves to be a win–win for all: remarkable privacy recovery for people with evident costs reduction for service providers.
Putting Wronging First
Authors: Webber Daniel
Published: January 2024

I argue that an act can be wrong because it wrongs a particular person. I then show how this thesis serves as a constraint on moral theories, using Kantian ethics as a case study.
Whose Uptake Matters? Sexual Refusal and the Ethics of Uptake
Authors: Harrison Rebecca E , Tanter Kai
Published: January 2024

What role does audience uptake play in determining whether a speaker refuses or consents to sex? Proponents of constitution theories of uptake argue that which speech act a speaker performs is largely determined by their addressee's uptake. However, this appears to entail a troubling result: a speaker might be made to perform a speech act of consent against her will. In response, we develop a Social Constitution Theory of uptake. We argue that addressee uptake can constitute a speaker's utterance of ‘no’ as a speech act of consent under some conditions, but that this does not prevent us from judging that an addressee committed rape. Second, we claim that addressee uptake is not the only form of uptake that matters—the uptake of other members of the discursive community matters too, and can override the addressee's uptake, constituting the speaker's utterance as the speech act it was intended to be.
Panax notoginsengstems and leaves affect microbial community and function in cecum of duzang pigs
Authors: Yi Lanlan , Zhu Junhong , Li Qiuyan , Guan Xuancheng , Cheng Wenjie , Xie Yuxiao , Zhao Yanguang , Zhao Sumei
Published: January 2024

Panax notoginseng is a Chinese medicine with a long history in which stems and leaves are the wastes of processing Panax notoginseng and have not been effectively utilized. The effects of diets containing Panax notoginseng stems and leaves on the cecal short-chain fatty acid (SCFA) concentration and microbiome of independent pigs were studied. Diets containing Panax notoginseng stems and leaves did not affect the concentration of SCFA in the cecal contents of Duzang pigs but affected the microbial composition and diversity. Firmicutes, Proteobacteria, and Bacteroidetes dominate in the cecal of Duzang pigs. Feeding Duzang pigs with a 10% Panax notoginseng stems and leaves diet increases the abundance of Lactobacillus, Christensenellaceae R-7 group, and Akkermansia in the cecal. We found 14 genera positively associated with acetate, and they were Lactobacillus, Ruminococcaceae UCG 005, Ruminiclostridium 6; Escherichia Shigella and Family XIII AD3011 group showed negative correlations. Solobacterium, Desulfovibrio, and Erysipelatoclostridium were positively associated with propionate. Campylobacter, Clostridium sensu stricto 11, and Angelakisella were positively associated with butyrate. In conclusion, Panax notoginseng stems and leaves could affect the cecal microbial community and functional composition of Duzang pigs. Panax notoginseng stems and leaves reduce the enrichment of lipopolysaccharide biosynthetic pathway of the cecal microbiome, which may have a positive effect on intestinal health. The higher abundance of GH25 family in Duzang pig’s cecal microbiome of fed Panax notoginseng stems and leaves diet. This increase may be the reason for the microbial diversity decrease.
Clinical Management Guidelines for Intrahepatic Cholestasis of Pregnancy
Authors:   Obstetrics Group of the Gynecology and Obstetrics Branch of Chinese Medical Association; Perinatal Medicine Branch of Chinese Medical Association, Yu Xinyang , Yang Huixia , Qi Hongbo
Published: January 2024

Intrahepatic cholestasis of pregnancy (ICP) is a significant gestational complication in late pregnancy, potentially leading to severe perinatal complications such as intrauterine fetal demise and preterm birth. The Obstetrics Group of the Gynecology and Obstetrics Branch and the Perinatal Medicine Branch of the Chinese Medical Association organized a panel of domestic experts to deliberate and propose recommendations based on domestic and international guidelines, recent evidence-based medical evidence about key clinical issues including risk factors, clinical manifestations, perinatal outcomes, diagnosis, severity grading, maternal and fetal monitoring, treatment methods, timing, and methods of pregnancy termination, and postpartum follow-up for ICP, with the aim to guide its clinical diagnosis, treatment, and management.
Diagnostic Reference Levels of Radiographic and CT Examinations in Jordan: A Systematic Review
Authors: Alzyoud Kholoud , Al-Murshedi Sadeq , England Andrew
Published: January 2024

A comprehensive search was performed to examine the literature on diagnostic reference levels (DRL) for computed tomography (CT) and radiography examinations that are performed routinely in Jordan. EBSCO, Scopus, and Web of Science were used for the search. The acronym “DRL” and the additional phrase “dose reference levels” were used to search for articles in literature. Seven papers that reported DRL values for radiography and CT scans in Jordan were identified. One study reported DRLs for conventional radiography, two studies reported CT DRLs in pediatrics, and the remaining four studies provided DRL values for adult CT scans. The most popular techniques for determining the DRLs were the entrance surface dose, volume CT dose index (CTDIvol), and dose-length product (DLP) values. Variations in Jordanian DRL values were noted across both modalities. Lower radiation doses and less variation in DRL values may be achieved by educating and training radiographers to better understand dose reduction strategies. To limit dose variance and enable dosage comparison, CT DRLs must be standardized in accordance with the guidelines of the International Commission on Radiological Protection (ICRP).
Retrospective Analysis of a New Intrastromal Dissection Technique Using the Retinal Reflex for Deep Anterior Lamellar Keratoplasty
Authors: Cho Soo Yeon , Yoon Ji Hyun , Koo Minjeong A. , Whang Woong Joo , Na Kyung-Sun , Kim Eun Chul , Kim Hyun Seung , Hwang Ho Sik
Published: January 2024

Purpose:

The purpose of this study was to describe a new surgical technique for deep anterior lamellar keratoplasty.

Methods:

All pupils in the recipient eyes were dilated preoperatively. Vertical grooving was performed using a crescent blade with a width of 5 mm and a depth of one-third to half corneal thickness on the temporal side of the limbus. Stromal dissection was performed as close as possible to Descemet membrane by observing the gap between the gold line by retinal reflex and the front edge of the crescent blade. Lamellar dissection was performed along the lamellar plane using corneal dissectors. The ophthalmic viscoelastic device was injected into the intrastromal pocket to separate the anterior and posterior stroma and an anterior corneal lamella was excised. A donor cornea was sutured into the recipient bed.

Results:

In 18 eyes, none of the patients had Descemet membrane rupture during surgery. The mean postoperative residual stromal thickness was 80 ± 31 μm. The mean central corneal thickness after surgery was 660 ± 69 μm. At the last follow-up, the cornea was cleared in all 18 eyes on slit-lamp examination.

Conclusions:

We estimated the residual stromal thickness based on the gap between the gold line by the retinal reflex and crescent blade, and intrastromal lamellar dissection was performed using a smooth corneal dissector. Consequently, the surface of stromal dissection was smooth, and the residual stromal thickness was even.
Comparison of 20% SF6 and 6% C3F8 Gas for Anterior Chamber Tamponade in Endothelial Keratoplasty
Authors: Wiley Zachary C. , Huang Xiaofan , Staggers Kristen A. , Hamill M. Bowes
Published: January 2024

Purpose:

The aim of this study was to compare the rates of rebubbling after Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping endothelial keratoplasty (DSEK) between patients who had anterior chamber (AC) graft tamponade with 20% sulfur hexafluoride gas (SF6) and 6% perfluoropropane gas (C3F8).

Methods:

The charts of 431 patients undergoing EK from June 8, 2010, to April 16, 2023, were reviewed. Patients undergoing EK alone as well as combined procedures with cataract extraction and intraocular lens implantation were included. Eyes with tube shunts, anterior chamber intraocular lenses, and large peripheral iridotomy with posterior loss of bubble, and patients undergoing cyclophotocoagulation or synechialysis were excluded. All rebubble procedures were performed within 1 month after initial surgery.

Results:

A total of 346 eyes using SF6 and 167 eyes using C3F8 were analyzed. Overall, 46 eyes (9%) required rebubbling; 33 eyes (10%) in the SF6 group and 13 eyes (8%) in the C3F8 group. For those patients undergoing DMEK, the odds of requiring rebubbling in the C3F8 group were about 22% lower than that of patients in the SF6 group (operating room [OR]: 0.782; P < 0.001). For patients undergoing DSEK, however, the gas type did not significantly affect rebubbling rates (P = 0.99).

Conclusions:

For DMEK, utilization of 6% C3F8 as an AC tamponade was associated with a significantly lower odds of graft rebubbling compared with 20% SF6. Gas type did not result in a significant difference for DSEK. Utilization of 6% C3F8 for graft tamponade could be considered to reduce graft detachment rates in DMEK.