bluuebunny/crossref_metadata_2025 huggingface dataset:
Over 4 Years of Safety and Efficacy with Voxelotor in Patients with Sickle Cell Disease
Authors: Brown Clark , Davis Mark , Achebe Maureen , Hassab Hoda , Al-Kindi Salam , Telfer Paul , Biemond Bart J , Lipato Thokozeni , Gray Sarah , Gordeuk Victor R
Published: June 2024

Presentation Date: 6/9/2024

Presentation Start Time: 1:33:00 PM

Background

In patients with sickle cell disease (SCD), polymerization of sickle hemoglobin (HbS) results in red blood cell sickling and leads to hemolysis, chronic anemia, and vaso-occlusive crises. Voxelotor, a first-in-class HbS polymerization inhibitor, is approved in the United States and Europe for the treatment of patients with SCD aged ≥4 years and ≥12 years, respectively. To assess the safety and efficacy of long-term voxelotor use, we report an updated interim analysis of an open-label extension (OLE) of the HOPE phase 3 trial (NCT03036813).

Methods

Patients who completed the HOPE trial were eligible to enroll in the multicenter, global OLE study (NCT03573882) and received ongoing treatment consisting of once daily voxelotor 1500 mg if they continued to derive clinical benefit. Adverse event (AE) data were collected through 28 days after voxelotor discontinuation, and measurements of hemoglobin and clinical markers of hemolysis were summarized through 168 weeks of treatment in the OLE. Data are based on an interim data cut (December 31, 2022).

Results

Of 199 patients who completed the HOPE trial, 178 (89.4%) were enrolled and dosed in the OLE. Median age at enrollment was 25 years. The median duration of voxelotor exposure in the OLE was 124.0 weeks, and 81 patients were treated for ≥168 weeks. Of these, 52 had received voxelotor in the HOPE trial, for a combined duration of exposure of ≥ 240 weeks. Patients previously treated with placebo in the HOPE trial had a mean (SD) hemoglobin change from baseline (start of OLE) of 1.1 (1.51) g/dL at Week 168. The mean (SD) hemoglobin change from baseline for patients who previously received voxelotor 1500 mg was 0.5 (1.49) g/dL (n = 18), indicating durability of response with continued treatment. Markers of hemolysis (indirect bilirubin, reticulocyte percentage) improved in patients who received placebo in the HOPE trial and were stable for patients who previously received 1500 mg voxelotor in the HOPE trial. Non-SCD-related treatment-emergent AEs (TEAEs) were reported in 88.2% of patients; no new safety signals were identified. Most TEAEs were grade 1 or 2 in severity. Eight deaths occurred, none deemed related to voxelotor treatment.

Conclusions

In this updated analysis from the HOPE OLE, long-term use of voxelotor was effective at improving hemoglobin and clinical markers of hemolysis in patients with SCD. The safety profile in the OLE was consistent with findings from the HOPE trial, and no new safety signals were identified with exposure through a combined 240 weeks of treatment.

© American Society of Hematology (2023). Reused with permission.
Incidence of Thromboembolic Events in Patients with Sickle Cell Disease Taking Voxelotor
Authors: Ansari Muneeb , Zhang Xu , Rizvi Insia , Farooqui Marwah
Published: June 2024

Presentation Date: 6/9/2024

Presentation Start Time: 2:09:00 PM

Background

Voxelotor was approved for patients with sickle cell in 2019 and acts to increase the hemoglobin in patients with severe hemolysis. Given hemoglobin’s contribution to hypercoagulable states, there is a concern that medications increasing hemoglobin concentrations may increase viscosity and contribute to thromboembolic events. This concern was furthered by a case report of a pulmonary embolism in a patient immediately after starting voxelotor.

Methods : This retrospective cohort study analyzed adult and pediatric patients ages 7 to 66 years of age with HbSS and HbSβ0 type sickle cell disease at the University of Illinois Health Sickle Cell Center started on voxelotor between January 2020 and October 2023. The charts of these patients were reviewed for cerebrovascular accident, pulmonary embolism, or deep vein thrombosis post voxelotor initiation.

Labs at the time of the thromboembolic event were recorded and the time between starting voxelotor and the event was calculated.

Results

In total, 84 patient charts were assessed. 24 were exclusively on voxelotor without hydroxyurea, L-glutamine, or crizanlizumab disease-modifying therapy. 10 patients (6 men and 4 women) had thromboembolic events (12%). Of those patients, 4 (2 men and 2 women) were in the voxelotor-only group.

Conclusion

Out of 84 adult and pediatric patients with sickle cell disease on voxelotor, 10 experienced thromboembolic events ranging from 1-29 months after starting the medication. Advanced age and history of a previous VTE were significantly associated with an increased risk of a subsequent VTE. The majority were unprovoked. Further research into characterizing the medication’s risk is warranted.
Systematic Review of Emergency Department Management of Vaso-occlusive Crisis
Authors: Hutcherson Timothy C , Cieri-Hutcherson Nicole , Rowlee Paige , Abeles Jennifer
Published: June 2024

Presentation Date: 6/9/2024

Presentation Start Time: 3:45:00 PM

Purpose

The objective of this systematic review was to characterize the management of vaso-occlusive crisis (VOC) in adult patients with sickle cell disease (SCD) in the emergency department (ED).

Methods

A literature search was conducted spanning origin through May 31, 2023, using Embase, MEDLINE ALL, and International Pharmaceutical Abstracts databases. Primary literature reporting on adult patients with SCD in a SCD-specific pathway or protocol in an ED setting was included. Data extracted included study design characteristics, patient demographics, descriptors of the pathway/protocol, and outcomes related to patient pain, pain medications, and hospital length of stay. The Cochrane Risk of Bias 2.0 tool was used to assess risk of bias (ROB) in randomized controlled trials (RCTs). The Risk of Bias for Non-Randomized Studies of Interventions was used to assess ROB in nonrandomized trials (NRTs). Certainty of evidence was assessed via the Grading of Recommendations, Assessment, Development, and Evaluations tool. This systematic review was not registered or funded.

Results

A total of 9 studies met eligibility criteria: 2 RCTs, 7 observational NRTs. RCTs had low ROB; of the 7 NRT studies, 5 had moderate ROB, and 2 had serious ROB. Improvements in time to first opioid, ED pain scores, length of ED treatment time, overall treatment time (length of stay), and inpatient readmission improved with policies or protocols for the management of VOC in the ED setting. These five outcomes had a moderate certainty of evidence.

Conclusion

Institutions should consider implementing protocols or pathways to improve management of VOC in the ED.
Menopause in Women with Sickle Cell Disease
Authors: Adedeji Monica , Andrews Elizabeth , Riddick-Burden Gaye , Rizk Sanaa
Published: June 2024

Presentation Date: 6/9/2024

Presentation Start Time: 4:15:00 PM

Background

Sickle cell disease (SCD) is the most common genetic disorder globally. With improved SCD management over the decades, more focus has been directed on long-term survival, and age-related complications. While menarche has been studied in adolescents with SCD and seems to be delayed, since women with SCD previously did not live long enough to experience menopause, there remains a paucity of data on menopause so far. This study sought to illicit the menopause experience in women with SCD including the age of onset and symptom severity. We hypothesized that women with SCD may have earlier onset menopause compared to women without SCD as reports have mentioned ovarian sickling as a proposed mechanism of premature ovarian failure, and iron overload as a possible cause of endocrinopathy--leading to impaired ovarian reserve.

Methods

Within the Jefferson Health Network, 37 menopausal Black women with SCD were interviewed using a standardized questionnaire inquiring about their menopause experience. Mean, median and standard deviation were calculated using basic statistics.

Results

Women with SCD, irrespective of genotype, underwent menopause at a median age of 48 years compared to 52 years--the national median age of menopause in Black women. Furthermore, women not on hydroxyurea had an increased incidence of menopausal symptoms including weight gain, hot flashes, sleep disturbances, vaginal dryness and mood swings, compared to women taking hydroxyurea.

Conclusions

While this study’s results are limited due to small sample size, it sheds light on the menopause experience in women with SCD and further highlights the need for further research on this topic.

Clinical Data of Menopause in Women with Sickle cell disease (SCD) With and Without Hydrea Therapy
Nontraumatic Epidural Hematoma in Sickle Cell Disease
Authors: Paros Alexandra
Published: June 2024

Presentation Date: 6/8/2024

Presentation Start Time: 6:00:00 PM

Background

Non-traumatic epidural hematoma is an extremely rare finding in patients with sickle cell disease. Spontaneous intracranial epidural hemorrhage has been associated with coagulopathy, malignancy, and infection, but few cases secondary to sickle cell disease have been reported in the literature. The mechanism of hemorrhage in these patients is often unclear, although previous cases have suggested associations with vaso-occlusive pain crises, bone infarction, and/or vascular malformations.We report a 9 year old male with sickle cell disease type SS who presented with right shoulder pain, headaches, emesis, and no neurological deficits. CT head revealed large mixed density left frontoparietal epidural hematoma leading to complete left lateral ventricle effacement and 0.5 cm left to right midline shift.

Methods

Chart review was performed through the electronic medical record to obtain information about the patient and case.

Results

The patient underwent a left parietal craniotomy for evacuation of epidural hematoma from which he recovered well.

Conclusions

Although rare, atraumatic epidural hematoma in SCD is associated with significant risk of morbidity and mortality. The prevalence and proposed pathologic process behind this rare complication will be discussed.
Sudden Death Caused by Plastic Bronchitis in a Child with Sickle Cell Disease
Authors: Morgan Epley , Lau Jaime , Hanna Cherry , Ahmed Rafat , Ostrowicki Renata , Krulish Sean , Nathan Anita
Published: June 2024

Presentation Date: 6/8/2024

Presentation Start Time: 6:00:00 PM

Background

Plastic bronchitis is a rare and poorly described complication of sickle cell disease and acute chest syndrome. It is defined as the formation of casts made of various materials, which obstruct lung bronchi. Plastic bronchitis has been diagnosed in several disease states including asthma, cystic fibrosis, and congenital heart disease following Fontan procedure. This case describes a case of a 5-year-old male with Sickle Cell SS Disease, admitted for pain crisis and Acute Chest Syndrome, which rapidly progressed to cardiovascular decompensation and death secondary to diffuse lung infiltration and obstruction due to plastic bronchitis.

Methods

Single case report

Results

A 5-year-old male with Sickle Cell SS Disease and moderate persistent asthma was admitted to the pediatric ward for generalized abdominal pain and extremity pain consistent with vaso-occlusive pain crisis. Subsequently, the patient developed a fever associated with respiratory distress and pain at his port-a-cath site. He was started on broad-spectrum antibiotics for Acute Chest Syndrome, given a new lung infiltrate in the right lower lobe on chest x-ray, and possible central line-associated bloodstream infection (CLABSI). He was initiated on high-flow nasal cannula (HFNC) and transferred to the pediatric intensive care unit. His respiratory status stabilized on HFNC with moderate supplemental oxygen and intermittent albuterol; however, he continued to have persistent tachycardia, tachypnea, and worsening lung infiltrates on repeat chest x-ray. Several hours later, he went into sudden cardiac arrest with asystole. Despite immediate CPR, intubation, and resuscitative measures, the patient expired. The autopsy revealed plastic bronchitis with fibrinous casts with 95% airway occlusion from the carina to the bronchioles in both lung fields.

Conclusions

Plastic bronchitis, a rare complication, can progress to rapid deterioration and death in pediatric patients with acute chest syndrome and sickle cell disease. The presentation of plastic bronchitis in sickle cell disease is unique compared to other underlying disease states. Clinicians should be on high alert for signs and symptoms indicating this potential complication, especially worsening chest radiographs in a patient with acute chest syndrome.
Mammography in Women with Sickle Cell Disease
Authors: Elmileik Eiman , Farooqui Marwah , Zhang Xu , Hussain Faiz , Haqqani Rayyan , Sung Kaitlin , Saraf Santosh L
Published: June 2024

Presentation Date: 6/8/2024

Presentation Start Time: 6:00 PM

Background

Sickle cell disease (SCD) is one of the most common inherited blood disorders and is associated with significant morbidity and reduced life expectancy. With advances in disease-modifying medications, morbidity and mortality are improved, and research focusing on cancer screenings becomes more relevant. This study aims to identify patterns regarding breast cancer screening, breast composition, and whether guidelines for the general population are appropriate for SCD patients.

Methods

This is a single-center retrospective study in which medical records of 156 individuals with SCD between 2018 and 2022 were analyzed.

Results

The average age of screening mammography was 44. Of the total individuals included in this study, 56% had screening mammography within the past two years (2021 and 2022); when compared to most recent CDC data from 2019, 70.8% of non-Hispanic Black women aged 40 and over had screening mammography within the past two years (2018 and 2019). With a binomial test, the difference was not statistically significant. 54% of those screened had dense breasts. Regression analysis data revealed an inverse relationship between BMI and screening age, and breast density; however, only the relationship between BMI and breast density was statistically significant.

Conclusion

This study was limited by sample size and its retrospective nature. Despite these constraints, this research contributes valuable insights into breast cancer screening practices and breast composition in individuals with SCD. Prospective studies with larger cohorts are recommended to enhance generalizability and foster a comprehensive understanding of cancer risks and screening patterns in this vulnerable patient population.
Damages and Their Quantification
Authors: Caro de Sousa Pedro
Published: June 2024

This chapter discusses the quantification of damages. It explains that the quantification of harm in competition cases is subject to considerable limits due to the degree of certainty and precision that can be achieved. In practice, the amount that a claimant may obtain in damages proceedings can depend on different factors, such as the impact of interest, and the relationship between the harm suffered and the amount of damages awarded. The chapter then elaborates further on the differences between compensatory damages, punitive damages, and exemplary damages. It also considers the efforts to promote public enforcement affecting the extent of the liability for damages of some participants in anti-competitive conduct.
Safeguarding Financial Stability in China
Authors: Li Bo , He Pengyu
Published: June 2024

This chapter covers the legal and institutional framework for safeguarding financial stability in China. In recent years, based upon China’s domestic circumstances and international best practices, the Chinese government has substantially reformed China’s financial stability institutional framework by (i) strengthening the overall coordination of financial stability work; (ii) improving the macroprudential policy framework; (iii) further rationalizing the financial regulatory systems and (iv) enhancing resolution mechanisms. The proposed "Draft Financial Stability Law" would further bolster China’s legal and institutional framework for financial stability by (i) strengthening the legal foundation of the coordination mechanism for financial stability; (ii) putting the central bank’s critical role in the macroprudential policy framework on a firmer legal footing and (iii) upgrading the legal framework for systemic risk resolution. Future reforms should continue to improve China’s financial regulatory systems and promote the appropriate separation of prudential supervision and conduct supervision.
The Evolution of the Regulatory Framework Governing Climate Change and Sustainable Finance in the EU and UK
Authors: Gortsos Christos V , Blair William
Published: June 2024

This chapter focuses on the evolution of the regulatory framework governing climate change and sustainable finance in the EU and the UK. It clarifies that sustainable finance is not limited to the climate change issue. The European Union (EU) has established a detailed rules-based sustainable finance legal structure (including a unique ‘Taxonomy framework’), while the United Kingdom (UK) developed an approach based on principles. The chapter tackles how the regulatory system is taking shape despite having no global consensus over the issue correlating to climate change and sustainable finance. According to the United Nations Conference on Trade and Development (UNCTAD), if the sector continues to grow, the sustainable investment market needs to address greenwashing concerns, the niche market risk, so that sustainable investment becomes a market norm, and the geographical imbalance of investments transforming the market from a developed-country phenomenon to a global market.
Legal Framework for Monetary Integration in West Africa—AfCFTA
Authors: Akin-Olugbade Adesegun
Published: June 2024

This chapter focuses on the African Continental Free Trade Agreement (AfCFTA), which is an agreement between 54 African countries to create a common market of over 1.2 billion people. AfCFTA was enacted as a direct solution to some of the seven aspirations of Agenda 2063, including social and economic development, integration, governance, peace, and security. Moreover, the agreement was expected to merge the markets by advocating for the free flow of people and goods. The chapter then elaborates on Agenda 2063, a 50-year development plan expected to result in an integrated Africa. It describes the attempts at monetary integration in West Africa prior to the AfCFTA and posits that the AfCFTA could finally provide the basis for achieving monetary integration in West Africa.
The UTMOST-NS: a fully digital, wide-field transient search facility operating at a centre frequency of 831 MHz
Authors: Mandlik A , Deller A T , Flynn C , Bailes M , Bateman T , Campbell-Wilson D , Day C K , Dunn L , Green A , Gupta V , Jameson A , Lee Y S C , Plant K , Price Danny C , Sekhri R , Sutherland A , Torr G , Urquhart G
Published: June 2024

The Molonglo Cross was first commissioned in 1965, as a transit radio (408 MHz) interferometer with the largest collecting area in the Southern hemisphere. In 1981, the telescope was redeveloped as an Earth-rotation synthesis interferometer using only the East–West arm (843 MHz), known as the Molonglo Observatory Synthesis Telescope. While the East–West arm was revitalized in the 2010s, the (slightly larger) North–South (NS) arm, which consists of two co-linear paraboloid cylindrical reflectors spanning 2 × 778 m × 12.7 m, had not been used for over 40 yr. Re-fitting this 19 800-m2 collecting area with modern electronics is a cost-effective way of producing a significant survey instrument. The upgrades made to the entire signal chain of the NS arm from the antenna through the transport, digitization, and digital signal processing are described, along with the subsequent performance of the system. The instrument was designed to undertake pulsar timing and searching for dispersed single pulses [e.g. from fast radio bursts (FRBs)]. The upgraded system operated across the 806.25–856.25-MHz frequency range, and had a primary beam that spans 12.7 × 2.5 deg. It had dual linear polarization capability and a lower system temperature and wider bandwidth compared with the East–West system. The digital signal processing was performed on servers with graphics processing units, which enabled low-latency, high-speed data processing, and made use of pipelines built from existing and custom codes. It timed around 70 pulsars per day while running concurrent FRB searches at nearly 100 per cent duty cycle during its operation.
Ensemble X-ray variability of optically selected QSOs: dependence on black hole mass and Eddington ratio
Authors: Georgakakis A , Buchner J , Ruiz A , Boller T , Akylas A , Paolillo M , Salvato M , Merloni A , Nandra K , Dwelly T
Published: June 2024

Although flux variability is one of the defining properties of accretion flows on to supermassive black holes, its dependence on physical parameters such as the mass of the compact object and the Eddington ratio remains under discussion. In this paper, we address this issue using the structure function statistic to measure the variability at X-ray wavelengths of a sample of optically selected QSOs with available black hole masses and Eddington ratios. We present a new Bayesian methodology for estimating the structure function tailored to the Poisson nature of the X-ray data. This is applied to 15 548 SDSS DRQ16 QSOs with repeat observations in the XMM–Newton archive and/or the SRG/eROSITA All Sky Survey. The X-ray structure function monotonically increases to time intervals of about 10–15 yrs, consistent with scenarios in which instabilities of the accretion disc contribute to the X-ray variability on long time-scales. Additionally, there is evidence that the amplitude of the stochastic X-ray flux variations rises with decreasing black hole mass and Eddington ratio. This finding imposes stringent constraints on empirical models of Active Galactic Nuclei variability derived from local samples, emphasizing the significance of high-redshift population studies for comprehending the stochastic flux variations in active black holes.
Probing hadron–quark phase transition in twin stars using f-modes
Authors: Pradhan Bikram K , Chatterjee Debarati , Alvarez-Castillo David Edwin
Published: June 2024

Although it is conjectured that a phase transitions from hadronic to deconfined quark matter in the ultrahigh-density environment of neutron stars (NS), the nature of phase transition remains an unresolved mystery. Furthermore, recent efforts reveal that the finite surface tension effects can lead to a mixed phase with different geometric shapes (so-called ‘pasta’ phases), leading to a smooth phase transition from hadronic to quark matter in the NS interior. Depending on whether there is a strong or a pasta-induced smooth first-order phase transition, one may expect a third family of stable, compact stars or ‘twin stars’ to appear, with the same mass but different radii compared to NSs. The possibility of identifying twin stars using astrophysical observations has been a subject of interest. This study investigates the potential of probing the nature of the hadron–quark phase transition through future gravitational wave (GW) detections from fundamental (f-) mode oscillations in NSs. Using a newly developed model that parametrizes the hadron–quark phase transition with ‘pasta phases’, we calculate f-mode characteristics within a full general relativistic framework. We then use universal relations in GW asteroseismology to derive stellar properties from the detected mode parameters. Our findings suggest that detecting GWs from f modes with third-generation GW detectors offers a promising scenario for the existence of twin stars. However, we also estimate various uncertainties in determining the mode parameters and conclude that these uncertainties make it more challenging to identify the nature of the hadron–quark phase transition.
phyloBARCODER: A Web Tool for Phylogenetic Classification of Eukaryote Metabarcodes Using Custom Reference Databases
Authors: Inoue Jun , Shinzato Chuya , Hirai Junya , Itoh Sachihiko , Minegishi Yuki , Ito Shin-ichi , Hyodo Susumu
Published: June 2024

We developed phyloBARCODER (https://github.com/jun-inoue/phyloBARCODER), a new web tool that can identify short DNA sequences to the species level using metabarcoding. phyloBARCODER estimates phylogenetic trees based on the uploaded anonymous DNA sequences and reference sequences from databases. Without such phylogenetic contexts, alternative, similarity-based methods independently identify species names and anonymous sequences of the same group by pairwise comparisons between queries and database sequences, with the caveat that they must match exactly or very closely. By putting metabarcoding sequences into a phylogenetic context, phyloBARCODER accurately identifies (i) species or classification of query sequences and (ii) anonymous sequences associated with the same species or even with populations of query sequences, with clear and accurate explanations. Version 1 of phyloBARCODER stores a database comprising all eukaryotic mitochondrial gene sequences. Moreover, by uploading their own databases, phyloBARCODER users can conduct species identification specialized for sequences obtained from a local geographic region or those of nonmitochondrial genes, e.g. ITS or rbcL.
Targeting IGF2 to reprogram the tumor microenvironment for enhanced viro-immunotherapy
Authors: Noh Min Hye , Kang Jin Muk , Miller Alexandra A , Nguyen Grace , Huang Minxin , Shim Ji Seon , Bueso-Perez Alberto J , Murphy Sara A , Rivera-Caraballo Kimberly A , Otani Yoshihiro , Kim Eunju , Yoo Seung-Hee , Yan Yuanqing , Banasavadi-Siddegowda Yeshavanth , Nakashima Hiroshi , Chiocca E Antonio , Kaur Balveen , Zhao Zhongming , Lee Tae Jin , Yoo Ji Young
Published: June 2024

Background

The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME).

Methods

RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance.

Results

Transcriptome analysis identified IGF2 as one of the top-secreted proteins following oHSV treatment. Moreover, IGF2 expression was significantly upregulated in 10 out of 14 recurrent GBM patients after treatment with oHSV, rQNestin34.5v.2 (71.4%; P = .0020) (ClinicalTrials.gov, NCT03152318). Depletion of IGF2 substantially enhanced oHSV-mediated tumor cell killing in vitro and improved survival of mice bearing BCBM tumors in vivo. To mitigate the oHSV-induced IGF2 in the TME, we constructed a novel oHSV, oHSV-D11mt, secreting a modified IGF2R domain 11 (IGF2RD11mt) that acts as IGF2 decoy receptor. Selective blocking of IGF2 by IGF2RD11mt significantly increased cytotoxicity, reduced oHSV-induced neutrophils/PMN-MDSCs infiltration, and reduced secretion of immune suppressive/proangiogenic cytokines, while increased CD8 + cytotoxic T lymphocytes (CTLs) infiltration, leading to enhanced survival in GBM or BCBM tumor-bearing mice.

Conclusions

This is the first study reporting that oHSV-induced secreted IGF2 exerts a critical role in resistance to oHSV therapy, which can be overcome by oHSV-D11mt as a promising therapeutic advance for enhanced viro-immunotherapy.
Chronic Liver Enzyme Elevation and Use of Contemporary ARVs Among People With HIV
Authors: Roen Ashley O , Peters Lars , Wandeler Gilles , van der Valk Marc , Zangerle Robert , Günthard Huldrych F , Wit Ferdinand , Mussini Cristina , De Wit Stéphane , d’Arminio Monforte Antonella , Vehreschild Jörg Janne , Castagna Antonella , Jaschinski Nadine , Vannappagari Vani , Chen Linda , Tallada Joan , C’mar John , Mocroft Amanda , Ryom Lene
Published: June 2024

Background

While use of some older antiretroviral drugs (ARVs) is associated with chronic liver enzyme elevation (cLEE), the impact of newer ARVs remains unknown.

Methods

People with HIV enrolled in the RESPOND cohort who started an ARV after January 1, 2012 were included (baseline). The primary outcome was first cLEE individuals were censored at first of cLEE, last visit, death, or December 31, 2021. Incidence rates (IRs; events/1000 person-years) were calculated for each ARV overall and by ARV exposure (6–12 months, 1–2 years, and 2+ years). Poisson regression was used to estimate the incidence rate ratio (IRR) of cLEE and its association with individual ARVs and ARV class.

Results

Of 17 106 individuals included contributing 87 924 person-years of follow-up, 1932 (11.3%) experienced cLEE (incidence rate [IR], 22.0; 95% CI, 21.0–23.0). There was no evidence of a cumulative ARV effect on cLEE incidence, (6–12 months: IR, 45.8; 95% CI, 41.4–50.19; 1–2 years: IR, 34.3; 95% CI, 31.5–37.4; and 2+ years: IR, 18.5; 95% CI, 17.4–19.7). Any use (vs no prior use) of non-nucleoside reverse transcriptase inhibitors (NNRTIs) as a class and tenofovir disoproxil fumarate (TDF) was independently associated with an increased IRR of cLEE, and any use of darunavir (DRV) was associated with a decreased risk of cLEE.

Conclusions

cLEE is common and more frequent during the first year after initiating new ARVs. With a >5-year median follow-up, we found no short-term liver safety concerns with the use of INSTIs. Use of NNRTIs and TDF was associated with an increased cLEE risk, while DRV was associated with lower risk.
Broad-band non-thermal emission of odd radio circles induced by explosive galactic outflow remnants and their evolution
Authors: Fujita Yutaka , Kawanaka Norita , Inoue Susumu
Published: June 2024

Odd radio circles (ORCs) are mysterious rings of faint, diffuse emission recently discovered in radio surveys, some of which may be associated with galaxies in relatively dense environments. We propose that such ORCs are synchrotron emission from remnants of explosive galactic outflows, calling them OGREs, and discuss their broad-band non-thermal emission and evolution. We posit that a large amount of energy was ejected from the central galaxy in the past, creating an outgoing shock that accelerates cosmic rays. Assuming plausible values for the density, temperature and magnetic field of the ambient medium, consistency with the observed spectral index, size, and power of the ORCs requires the energy to be as high as ∼1060 erg, suggesting that their sources could be active galactic nuclei. We calculate the spectral energy distributions (SEDs) of the OGREs and their evolution, including synchrotron, inverse Compton (IC), and bremsstrahlung emission from electrons, and pion-decay emission from protons. We find that the SEDs of the younger OGREs are not greatly different from those of older ones currently observable as ORCs if radiative cooling of electrons is effective. As such younger OGREs are expected to be rarer and smaller, they may not be readily observable. However, if radiative cooling of electrons is ineffective, younger OGREs may be detectable in X-rays.
Absence of alka(e)nes triggers profound remodeling of glycerolipid and carotenoid composition in cyanobacteria membrane
Authors: Miao Rui , Légeret Bertrand , Cuine Stéphan , Burlacot Adrien , Lindblad Peter , Li-Beisson Yonghua , Beisson Fred , Peltier Gilles
Published: June 2024

Alka(e)nes are produced by many living organisms and exhibit diverse physiological roles, reflecting a high functional versatility. Alka(e)nes serve as waterproof wax in plants, communicating pheromones for insects, and microbial signaling molecules in some bacteria. Although alka(e)nes have been found in cyanobacteria and algal chloroplasts, their importance for photosynthetic membranes has remained elusive. In this study, we investigated the consequences of the absence of alka(e)nes on membrane lipid composition and photosynthesis using the cyanobacterium Synechocystis PCC6803 as a model organism. By following the dynamics of membrane lipids and the photosynthetic performance in strains defected and altered in alka(e)ne biosynthesis, we show that drastic changes in the glycerolipid contents occur in the absence of alka(e)nes, including a decrease in the membrane carotenoid content, a decrease in some digalactosyldiacylglycerol (DGDG) species and a parallel increase in monogalactosyldiacylglycerol (MGDG) species. These changes are associated with a higher susceptibility of photosynthesis and growth to high light in alka(e)ne-deficient strains. All these phenotypes are reversed by expressing an algal photoenzyme producing alka(e)nes from fatty acids. Therefore, alkenes, despite their low abundance, are an essential component of the lipid composition of membranes. The profound remodeling of lipid composition that results from their absence suggests that they play an important role in one or more membrane properties in cyanobacteria. Moreover, the lipid compensatory mechanism observed is not sufficient to restore normal functioning of the photosynthetic membranes, particularly under high-light intensity. We conclude that alka(e)nes play a crucial role in maintaining the lipid homeostasis of thylakoid membranes, thereby contributing to the proper functioning of photosynthesis, particularly under elevated light intensities.
A COBRA family protein, PtrCOB3, contributes to gelatinous layer formation of tension wood fibers in poplar
Authors: Xu Wenjing , Cheng Hao , Cheng Jiyao , Zhu Siran , Cui Yongyao , Wang Chong , Wu Jianzhen , Lan Xingguo , Cheng Yuxiang
Published: June 2024

Angiosperm trees usually develop tension wood (TW) in response to gravitational stimulation. TW comprises abundant gelatinous (G-) fibers with thick G-layers primarily composed of crystalline cellulose. Understanding the pivotal factors governing G-layer formation in TW fiber remains elusive. This study elucidates the role of a Populus trichocarpa COBRA family protein, PtrCOB3, in the G-layer formation of TW fibers. PtrCOB3 expression was upregulated, and its promoter activity was enhanced during TW formation. Comparative analysis with wild-type trees revealed that ptrcob3 mutants, mediated by Cas9/gRNA gene editing, were incapable of producing G-layers within TW fibers and showed severely impaired stem lift. Fluorescence immunolabeling data revealed a dearth of crystalline cellulose in the tertiary cell wall (TCW) of ptrcob3 TW fibers. The role of PtrCOB3 in G-layer formation is contingent upon its native promoter, as evidenced by the comparative phenotypic assessments of pCOB11::PtrCOB3, pCOB3::PtrCOB3, and pCOB3::PtrCOB11 transgenic lines in the ptrcob3 background. Overexpression of PtrCOB3 under the control of its native promoter expedited G-layer formation within TW fibers. We further identified 3 transcription factors that bind to the PtrCOB3 promoter and positively regulate its transcriptional levels. Alongside the primary TCW synthesis genes, these findings enable the construction of a 2-layer transcriptional regulatory network for the G-layer formation of TW fibers. Overall, this study uncovers mechanistic insight into TW formation, whereby a specific COB protein executes the deposition of cellulose, and consequently, G-layer formation within TW fibers.
Tubulin participates in establishing protoxylem vessel reinforcement patterns and hydraulic conductivity in maize
Authors: Huang Shiquan , Guo Siyi , Dai Liufeng , Mi Lingyu , Li Wenrao , Xing Jingjing , Hu Zhubing , Wu Wenqiang , Duan Zhikun , Li Baozhu , Sun Ting , Wang Baojie , Zhang Yi , Xiao Tiqiao , Xue Yanling , Tang Ning , Li Han , Zhang Changqing , Song Chun-Peng
Published: June 2024

Water transportation to developing tissues relies on the structure and function of plant xylem cells. Plant microtubules govern the direction of cellulose microfibrils and guide secondary cell wall formation and morphogenesis. However, the relevance of microtubule-determined xylem wall thickening patterns in plant hydraulic conductivity remains unclear. In the present study, we identified a maize (Zea mays) semi-dominant mutant, designated drought-overly-sensitive1 (ZmDos1), the upper leaves of which wilted even when exposed to well-watered conditions during growth; the wilting phenotype was aggravated by increased temperatures and decreased humidity. Protoxylem vessels in the stem and leaves of the mutant showed altered thickening patterns of the secondary cell wall (from annular to spiral), decreased inner diameters, and limited water transport efficiency. The causal mutation for this phenotype was found to be a G-to-A mutation in the maize gene α-tubulin4, resulting in a single amino acid substitution at position 196 (E196K). Ectopic expression of the mutant α-tubulin4 in Arabidopsis (Arabidopsis thaliana) changed the orientation of microtubule arrays, suggesting a determinant role of this gene in microtubule assembly and secondary cell wall thickening. Our findings suggest that the spiral wall thickenings triggered by the α-tubulin mutation are stretched during organ elongation, causing a smaller inner diameter of the protoxylem vessels and affecting water transport in maize. This study underscores the importance of tubulin-mediated protoxylem wall thickening in regulating plant hydraulics, improves our understanding of the relationships between protoxylem structural features and functions, and offers candidate genes for the genetic enhancement of maize.
Federal Judges, States Legislators, and State Voting Rights Rollback
Authors: Woodward-Burns Robinson
Published: June 2024

This article claims that recent Supreme Court decisions have allowed state lawmakers to suppress and skew but not subvert the vote. The Court relaxed federal oversight of state election administration in Shelby County v. Holder (2013), Abbott v. Perez (2018), and Brnovich v. Democratic National Committee (2021), and gerrymandering in Rucho v. Common Cause (2019), while prohibiting independent state legislative election regulation in Moore v. Harper (2023). These decisions guided state lawmakers toward vote suppression and skewing, and away from election subversion. Consequently, Republican state legislatures have passed state constitutional amendments and statutes limiting ballot access and reforming state redistricting practices. While some Democratic state legislatures have protected ballot access and independent redistricting, these recent Supreme Court decisions help Republicans win a disproportionate share of state legislative seats. National courts thus help preserve the national party coalition by opening subnational jurisdictions to party entrenchment.
Motivic Geometry of two-Loop Feynman Integrals
Authors: Doran Charles F , Harder Andrew , Vanhove Pierre , Pichon-Pharabod Eric
Published: June 2024

We study the geometry and Hodge theory of the cubic hypersurfaces attached to two-loop Feynman integrals for generic physical parameters. We show that the Hodge structure attached to planar two-loop Feynman graphs decomposes into mixed Tate pieces and the Hodge structures of families of hyperelliptic, elliptic or rational curves depending on the space-time dimension. For two-loop graphs with a small number of edges, we give more precise results. In particular, we recover a result of Bloch (Double box motive. SIGMA 2021;17,048) that in the well-known double-box example, there is an underlying family of elliptic curves, and we give a concrete description of these elliptic curves. We show that the motive for the non-planar two-loop tardigrade graph is that of a K3 surface. In an appendix by Eric Pichon-Pharabod, we argue via high-precision numerical computations that the Picard number of this K3 surface is generically 11 and we compute the expected lattice polarization. Lastly, we show that generic members of the ice cream cone family of graph hypersurfaces correspond to the pairs of sunset Calabi–Yau varieties.
The thermoluminescence glow curves of LiF:Mg,Ti: characteristics and mechanisms
Authors: Horowitz Yigal Shalom , Oster Leonid
Published: June 2024

The features of the glow curves of LiF:Mg,Ti are dependent on many parameters of irradiation, storage, ionisation density and readout. These are presented herein with emphasis on their complexity. Successful applications require some understanding of the great diversity of the glow curves. Glow curve analysis/deconvolution in order to better understand the mechanisms is a ‘tricky business’ even with Tm-Tstop analysis. In the theoretical framework of spatially correlated trapping and luminescent centres, a mechanism is described which simulates the behaviour of composite peak 5 at different cooling rates and following photon bleaching at 3.65 eV.
Assessment of natural radioactivity in the RCC building materials used in the valley region of Manipur, India
Authors: Sharma Brahmacharimayum Arunkumar , Devi Angom Ronibala
Published: June 2024

An assessment of radioactivity concentration of reinforced cement concrete types of house was conducted in the valley region of Manipur, India. The average radioactivity concentration of 226Ra, 232Th, and 40K of portland cements are 39 (range: 32–52) Bqkg−1, 36 (range: 22–62) Bqkg−1, and 1812 (1254–2424) Bqkg−1; for concrete are 36 (range: 26–45) Bqkg−1, 65 (range: 45–86) Bqkg−1, and 660 (639–681) Bqkg−1; for sand are 45 (30–61) Bqkg−1, 114 (range: 55–212) Bqkg−1, and 1859 (range: 1413–2232) Bqkg−1; and for bricks are 30 (range: 24–37) Bqkg−1, 148 (range:79–184) Bqkg−1, and 1444 (range: 1093–2103) Bqkg−1, respectively. The annual effective dose was observed with an average value of 1.9 (range: 0.9–3.3) mSvy−1. However, gamma index was observed with an average value of 1.1 (range: 0.5–2.0).
The scent of cuteness—neural signatures of infant body odors
Authors: Schäfer Laura , Köppel Carina , Kreßner-Kiel Denise , Schwerdtfeger Sarah , Michael Marie , Weidner Kerstin , Croy Ilona
Published: June 2024

The smell of the own baby is a salient cue for human kin recognition and bonding. We hypothesized that infant body odors function like other cues of the Kindchenschema by recruiting neural circuits of pleasure and reward. In two functional magnetic resonance imaging studies, we presented infantile and post-pubertal body odors to nulliparae and mothers (N = 78). All body odors increased blood-oxygen-level-dependent (BOLD) response and functional connectivity in circuits related to olfactory perception, pleasure and reward. Neural activation strength in pleasure and reward areas positively correlated with perceptual ratings across all participants. Compared to body odor of post-pubertal children, infant body odors specifically enhanced BOLD signal and functional connectivity in reward and pleasure circuits, suggesting that infantile body odors prime the brain for prosocial interaction. This supports the idea that infant body odors are part of the Kindchenschema. The additional observation of functional connectivity being related to maternal and kin state speaks for experience-dependent priming.
Points of departure: family leave policy and women’s representation in management in U.S. workplaces
Authors: Mun Eunmi , Vican Shawna , Kelly Erin L
Published: June 2024

This paper theorizes the interplay of public and organizational policies by investigating whether the Family and Medical Leave Act (FMLA) shifted patterns of gender inequality within U.S. workplaces. Did this leave law increase women’s representation in positions of authority (moving more women into management jobs)? We argue that the impact of public policies will vary by organizational context, hypothesizing different effects by organizations’ points of departure—the corporate policies in place when public policy changes. Analyzing establishment-level panel data from approximately 800 U.S. private-sector establishments in 1990–1997, we found that women’s representation in managerial positions increased in the years immediately after the FMLA. Importantly, women’s representation in management increased the most in workplaces that provided more generous leave benefits even before the FMLA. The increase in managerial representation was most prominent for women of color. Consistent with relational inequality theory, these findings suggest that women may find it easier to make claims for leave and for career advancement when both legal and organizational policies lend legitimacy to their claims. More broadly, this study points to the need to explicitly evaluate how policy impacts vary by organizational norms and commitments.
Social Locations of Secularization and Worldview (Dis)Enchantment: Education, Income, and Belief in Religious and Paranormal Phenomena
Authors: Corcoran Katie E , Scheitle Christopher P , DiGregorio Bernard D
Published: June 2024

Forces of secularization are theorized to disenchant an individual’s worldview—i.e., erode an individual’s belief in nonnatural beings, forces, or abilities. Tests of this proposition, though, have often failed to measure the variety of forms of worldview enchantment found among individuals. Drawing on the broader secularization literature, we theorize correlates of (dis)enchantment and test these predictions using a nationally representative survey of U.S. adults featuring a wide battery of enchanted beliefs. We identify four latent enchanted worldview dimensions and find, consistent with secularization theories, that education and income are consistently and negatively associated with all four worldview enchantment dimensions.
The impact of gynecologic cancer on female sexuality in Europe and MENA (Middle East and North Africa): a literature review
Authors: Shams Malihe , Coman Claudia , Fatone Fabiola , Marenesi Vittoria , Bernorio Roberto , Feltrin Alessandra , Groff Elena
Published: June 2024

Introduction

Gynecologic cancer has a negative impact on the sexuality of women who are or have been affected by this disease. In fact, gynecologic cancers cause negative changes in female sexuality, affecting body image and psychophysical well-being, with serious consequences for women’s sex lives.

Objectives

The aim of this study is to analyze the differences in sexuality among women who have or have had gynecologic cancer in Europe and in the Middle East and North Africa (MENA). We also explored possible factors that may influence women’s sexuality in the 2 populations compared.

Methods

The literature search was carried out using PubMed and Google Scholar, considering the 10-year period of 2013 to 2023. Studies were initially selected according to the criterion that the title and abstract were in English. We then reviewed all the articles selected in the first phase and analyzed the following information: author, year of publication, type of gynecologic cancer, country in which the study was conducted, design, and materials used. Finally, we defined the inclusion criteria for the present paper: women 18 years of age or older, diagnosed with gynecologic cancer, and who had undergone treatment (surgery, chemotherapy, radiotherapy). The studies reviewed were conducted between 2013 and 2023 in Europe and MENA, and all analyzed sexual function after the disease, understood as a general dimension that includes physiological and psychological aspects.

Results

The results of this research show that patients in both geographical areas (Europe and MENA) report changes in sexuality as a result of the cancer. Studies show that cancer reduces, interrupts, and impairs women’s sexual activity, resulting in experiences of discomfort, anxiety, guilt, inadequacy, pain, and poorer quality of life.

Conclusions

The data analyzed in this review show that cancer causes changes and deterioration in sexuality in both populations studied. No cultural or social factors were found to cause differences between the variables studied in the 2 populations. In the future, it may be interesting to carry out further studies to improve the treatment of women with gynecologic cancer, as sexuality is a very important part of a person’s life.