bluuebunny/crossref_metadata_2025 huggingface dataset:
Pricing and Product Positioning with Relative Consumer Preferences*
Authors: Inderst Roman , Obradovits Martin
Published: September 2023

Frequent price promotions force consumers to continuously reassess their preferences over product offerings. When this leads consumers to exhibit a bias of “relative thinking”, such as may be triggered by a focus only on the most salient product attribute, we show in a model of sales (Varian, H. R., 1980, American Economic Review, 70(4), pp. 651–659) that this profoundly alters firms' pricing and product‐positioning strategies. Vertical differentiation becomes more likely, with firms preferring to occupy the low‐quality space in particular when they have few loyal consumers. More generally, product positioning now depends on the composition of consumers' consideration sets.
Risk factors, treatment, and outcome in dogs and cats with subdural hematoma and hemispheric collapse after ventriculoperitoneal shunting of congenital internal hydrocephalus
Authors: Farke Daniela , Siwicka Anna K. , Olszewska Agnieszka , Czerwik Adriana , Büttner Kathrin , Schmidt Martin J.
Published: September 2023

Background

Overshunting and hemispheric collapse are well‐known complications after ventriculoperitoneal shunt (VPS) implantation. Risk factors that predispose to overshunting, treatment options, and prognosis after therapeutic intervention have not been described.

Hypothesis/Objectives

To identify preoperative risk factors for overshunting, the effect of surgical decompression, and their outcomes.

Animals

Seventy‐five dogs and 7 cats.

Methods

Retrospective case cohort study. Age, breed, sex, body weight, number of dilated ventricles, ventricle brain ratio, intraventricular pressure, and implanted pressure valve systems were evaluated as possible risk factors.

Results

Overshunting had a prevalence of 18% (Cl 95% 9.9‐26.66). An increase of 0.05 in VBR increased the risk of overshunting by OR 2.23 (Cl 95% 1.4‐3.5; P = .001). Biventricular hydrocephalus had the highest risk for overshunting compared to a tri‐ (OR 2.48 with Cl 95% 0.5‐11.1) or tetraventricular hydrocephalus (OR 11.6 with Cl 95% 1.7‐81.1; P = .05). There was no influence regarding the use of gravitational vs differential pressure valves (P > .78). Overshunting resulted in hemispheric collapse, subdural hemorrhage, and peracute deterioration of neurological status in 15 animals. Subdural hematoma was removed in 8 dogs and 2 cats with prompt postoperative improvement of clinical signs.

Conclusions and Clinical Importance

Biventricular hydrocephalus and increased VBR indicate a higher risk for overshunting. The use of differential valves with gravitational units has no influence on occurrence of overshunting related complications and outcomes. Decompressive surgery provides a favorable treatment option for hemispheric collapse and has a good outcome.
Primary intraosseous carcinoma arising in a dentigerous cyst: A case report
Authors: Tousi Farnoush , Johannessen Anne Christine , Ljøkjel Borghild , Løes Sigbjørn
Published: September 2023

Dentigerous cysts are among the most common cysts of the jaw. They are attached to the crown of an unerupted tooth, most frequently third molars and maxillary canines. They are often asymptomatic and may therefore be diagnosed late. We report a case of a primary intraosseous carcinoma arising from the wall of a dentigerous cyst and describe the expression of typical genes associated with tumour growth and prognosis. The tumour expressed cytokeratins (CK) 5/6, 8, 14 and 19, but not CK7. Ki‐67 and P53 were upregulated in dysplastic epithelium and tumour tissue. Although rare, the possibility for tumour development in the wall of a common cyst should be considered. The case emphasizes the importance of histopathological examination of surgical specimens, even if the clinical diagnosis seems obvious.
The Genetic Causal Association between Educational Attainment and Risk of 12 Common Musculoskeletal Disorders: A Two‐Sample Mendelian Randomization
Authors: Sun Kaibo , Ming Yue , Wu Yuangang , Zeng Yi , Xu Jiawen , Wu Limin , Li Mingyang , Shen Bin
Published: September 2023

Objective

In numerous observational studies, there has been an indication that educational attainment (EA) can impact the intensity of pain and disability resulting from chronic musculoskeletal disorders. Nonetheless, the association observed in these studies is not entirely conclusive. The aim of this study was to investigate the genetic causal relationship between educational attainment and 12 musculoskeletal disorders using Mendelian randomization (MR).

Methods

The meta‐analysis of genome‐wide association studies (GWAS) identified 3952 single‐nucleotide polymorphisms (SNPs) associated with educational attainment (EA) from the Social Science Genetic Association Consortium (SSGAC). Genetic data for 12 musculoskeletal disorders, including osteonecrosis, osteoporosis, osteomyelitis, low back pain, gout, spinal stenosis, rheumatoid arthritis, meniscus derangement, rotator cuff syndrome, ankylosing spondylitis, cervicobrachial syndrome, and lateral epicondylitis, were obtained from the FinnGen consortium. We conducted a two‐sample Mendelian randomization analysis to examine the causal effect of EA on the risk of these musculoskeletal disorders using the TwoSampleMR package in R.

Results

Based on the inverse‐variance weighted (IVW) method, we found that a genetically predicted per standard deviation (SD) increase in EA was inversely associated with low back pain [odds ratio (OR) 0.46, 95% confidence interval (Cl) 0.51–0.61, p < 0.001], spinal stenosis (OR 0.62, 95% Cl 0.54–0.71, p < 0.001), rheumatoid arthritis (OR 0.65, 95% Cl 0.55–0.76, p < 0.001), meniscus derangement (OR 0.73, 95% Cl 0.65–0.82, p < 0.001), rotator cuff syndrome (OR 0.55, 95% Cl 0.49–0.61, p < 0.001), cervicobrachial syndrome (OR 0.50, 95% Cl 0.42–0.60, p < 0.001), and lateral epicondylitis (OR 0.30, 95% Cl 0.24–0.37, p < 0.001). There was no causal association between EA and osteonecrosis (OR 1.11, 95% CI 0.76–1.72, p = 0.60), osteoporosis (OR 0.91, 95% CI 0.65–1.27, p = 0.59), or osteomyelitis (OR 0.90, 95% CI 0.75–1.01, p = 0.22). Genetic predisposition to EA had a suggestive causal association with gout (OR 0.80, 95% CI 0.68–0.95, p = 0.01) and ankylosing spondylitis (OR 0.64, 95% CI 0.45–0.91, p = 0.01) after Bonferroni correction. None of the analyses revealed any horizontal pleiotropy or heterogeneity.

Conclusion

In our investigation, we have uncovered evidence supporting a causal relationship between low level of EA and the incidence of certain musculoskeletal disorders. In the future, it is imperative to ascertain risk factors such as lifestyle patterns linked with EA to uncover the underlying causal relationship and offer informed interventions for individuals.
Development of KASP fingerprinting panel for clonal identification in red raspberry (Rubus idaeus L.)
Authors: Clare Shaun J. , King Ryan M. , Hardigan Michael , Dossett Michael , Montanari Sara , Chagné David , Ochsenfeld Cherie , Britton Caitlin , Rapp Ryan , Bassil Nahla
Published: September 2023

Red raspberry is an economically important horticultural crop that is known for its fruit's sweet flavour and nutritional value. A reliable and economic genotyping platform is needed to facilitate clonal/variety identification. Previous attempts for clonal identification utilized morphological traits or low‐throughput, difficult to score dinucleotide‐containing simple sequence repeat molecular markers. Single nucleotide polymorphisms (SNPs), despite having lower allelic diversity, are numerous across the genome and more easily converted to high‐throughput assays restoring differential power. In this study, we use the kompetitive allele‐specific PCR (KASP™) chemistry, an affordable and high‐throughput platform, to develop a panel of SNPs to distinguish a diverse collection of red raspberry accessions for clonal identification. The panel consists of 48 KASP assays that show high concordance with whole genome sequencing, allelic balance, and recovery rate and a minimal set of 24 assays that distinguished the same accessions differentiated by the larger panel.
Missing out on effective care in idiopathic pulmonary fibrosis: Racial inequality in access to anti‐fibrotic therapy
Authors: Pascoe Amy , Smallwood Natasha
Published: September 2023

See related article
The shifting roles and toxicities of cellular therapies in B‐cell malignancies
Authors: Makos Olivia L. , D'Angelo Christopher R.
Published: September 2023

Cellular therapies provide a curative‐intent option for patients with relapsedand refractory lymphomas. Current options including high dose chemotherapyfollowed by autologous or allogeneic hematopoietic stem cell transplantation or CD19 chimericantigen receptor T‐cell (CART) therapy. The indication varies according to lymphoma sub‐type and line oftherapy. The sequencing of these therapies and their use in second‐line orlater settings to manage these diseases is undergoing significant changes, withCD19 CAR T becoming a preferred option for relapsed aggressive B‐cell lymphoma.The mechanism of both therapies causes significant yet distinctlymphodepletion, infectious, and inflammatory toxicities. The resulting patternand timing of immune reconstitution helps guide risk‐mitigating strategies,revaccination, and infectious prophylaxis. In this review, we discuss theindication, efficacy, toxicity and immune reconstitution of autologoushematopoietic stem cell transplantation and CAR T therapy for use in thetreatment of lymphoma.
Letermovir for pre‐emptive cytomegalovirus therapy after allogeneic hematopoietic cell transplantation
Authors: Kaur Raena , Purtill Duncan , Cooney Julian , Cannell Paul , Wright Matthew , Copeland Tandy‐Sue , McGuire Matthew , Boan Peter
Published: September 2023

Background

Cytomegalovirus (CMV) is a common cause of morbidity after allogeneic haematopoietic cell transplantation (alloHCT). Pre‐emptive therapy (PET) with valganciclovir (VGC) is associated with haematological toxicity.

Methods

We included alloHCT patients from 2018 to 2021 where letermovir (LTV) was used for CMV PET because of cytopenias.

Results

Ten patients were included. Six received VGC prior to LTV. VGC was commenced at median d42, given for median 40 days. LTV was commenced at median d90, given for median 54 days. At commencement of antiviral, CMV viral load was higher for VGC at 3.7 log10 IU/mL, compared to LTV at 2.9 log10 IU/mL. Viral load reduction occurred at 0.18 log10 IU/mL per week for VGC, compared to 0.17 log10 IU/mL per week for LTV. There was no clinically significant CMV viremia after stopping LTV. Cytopenias improved on LTV.

Conclusion

LTV was effective in controlling CMV viremia when it was given at a lower starting CMV viral load and later post alloHCT than VGC. Further study is required of LTV as upfront PET following alloHCT.

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Juvenile ocular abnormalities in a litter of black‐footed ferrets
Authors: Chan Kore , Climans Megan , Helmick Kelly , Garelle Della , Adkins Elizabeth A.
Published: September 2023

Objective

To describe the clinical and histopathological features of ocular abnormalities noted in a litter of black‐footed ferrets (Mustela nigripes), including corneal opacification, cataracts, persistent pupillary membranes, microphthalmia, symblepharon and anterior segment malformation.

Animals Studied

A litter of eight black‐footed ferrets examined at 10 weeks old with a history of ophthalmia neonatorum first noted at 7 days old and histopathological examination of three globes from three ferrets of the same litter between 5 and 7 months old following routine subconjunctival enucleation.

Procedures

Due to the fractious nature of black‐footed ferrets, slit‐lamp biomicroscopic examination was performed under general isoflurane anesthesia at 10 weeks of age. Corneal opacification was noted in 9/16 eyes, cataracts in 4/16 eyes, and persistent pupillary membranes in 3/16 eyes, among other findings. Histopathology revealed persistent pupillary membranes and Descemet's membrane abnormalities consistent with congenital anterior segment malformation in all three globes. In one ferret, a posterior cortical cataract with posterior lenticular malformation and lens capsule discontinuity was noted. Purulent discharge was cultured at time of enucleation in one ferret with growth of E. coli.

Conclusions

A novel constellation of ocular malformations with primary congenital and secondary to ophthalmia neonatorum etiologies is described in black‐footed ferrets. Due to endangered status of black‐footed ferrets, small genetic pool and the requirement for adequate vision for wild‐release, congenital ocular abnormalities such as anterior segment malformation and likely the cataracts described are of particular concern. Further investigation and monitoring are warranted to determine the heritability of these ocular abnormalities.
Design and Control of an Aerial Manipulator With Invariant Center of Gravity for Physical Interaction
Authors: Rong Yongfeng , Chou Wusheng
Published: September 2023

The deployment of manipulators enhances the versatility and flexibility of unmanned aerial vehicles (UAVs) in aerial physical interaction tasks but also challenges their designs and controls due to variations in the center of gravity (CoG), moment of inertia, and reaction wrenches. This work presents a novel design of a two-degree-of-freedom dual-tool manipulator with invariant-center-of-gravity (ICoG) property. The ICoG conditions are strictly deduced, and a practical optimization-based parameter tuning method is proposed. A novel adaptive extended state observer (AESO)-based impedance control method is developed with actuator dynamics taken into account. The AESO can estimate and compensate for both the lumped disturbance, including the influences of moment-of-inertia variation and counter torque, and the unmeasurable states for the controller. In addition, a switching adaptive law is proposed to attenuate the peaking phenomenon under high observer gains. The impedance controller is designed using an auxiliary impedance tracking error to overcome the difficulty of the increased system order. The Lyapunov approach is used to evaluate the stability of the entire system. The proposed approach is implemented on a fully actuated hexarotor with a prototype of the ICoG manipulator. Comparative experiments are conducted to validate the effectiveness and advantages of the proposed design and control methods.
Validation of Bayesian design for broadband microslit panel absorbers using causal inference
Authors: Xiang Ning , Hoeft Michael , Fackler Cameron J. , Chen Ziqi , Barach Paul
Published: September 2023

This paper discusses experimental validations of multilayer microslit panels (MSPs) designed via Bayesian inference to obtain both high sound absorption and wide bandwidth simultaneously. Microslit perforation in thin panels is similar to microperforated panels [Xiang, Fackler, Hou, and Schmitt (2022). J. Acoust. Soc. Am. 151(5), 3094–3103]. MSP absorbers in single-layer configurations are functioning in a limited frequency range. By stacking the MSPs in multiple layered structures, absorbing performance may be widened in frequency ranges while retaining high absorption coefficients. Besides design challenges of multiple MSPs in layered structures to fulfill a practical requirement and minimize fabrication complexity, this paper further discusses challenges in experimental validations when experimental results undesirably deviate from the initial Bayesian design. Causation analysis is applied to the validation efforts where a causal model-based inference effectively provides causal reasoning of fabrication inaccuracies. Along with the causal inference, a causal reasoning conducted in this work can guide corrections due to fabrication inaccuracies during the iterative validation process.
Handedness, Bilateral, and Interdigit Strength Asymmetries in Male Climbers
Authors: Hartley Cameron , Taylor Nicola , Chidley Joel , Baláš Jiří , Giles Dave
Published: September 2023

Purpose: To determine whether there are bilateral and interdigit differences in the maximal force production of experienced climbers and whether these differences are mediated by ability level or preferred style of climbing. Methods: Thirty-six male climbers (age 30 [9.4] y) took part in a single-session trial to test their maximal force production on both hands. The tests included a one-arm maximal isometric finger flexor strength test (MIFS) and a one-arm individual MIFS. Bilateral differences were analyzed by strongest hand (defined as the hand that produced the highest MIFS value) and dominance (defined as the writing hand). Results: A pairwise t test found that MIFS was significantly greater for the strongest hand (mean difference = 4.1%, 95% CI, −0.052 to 0.029, P < .001), with handedness explaining 89% of the variation. A 2-way mixed-model analysis of variance determined that there were no interactions between preferred style (bouldering or sport climbing) and MIFS or between ability level (advanced or elite) and MIFS. Conclusions: Climbers have significant finger flexor strength bilateral asymmetries between their strongest and weakest hand. Moreover, when dominance is controlled, this difference in strength is present, with the dominant hand producing more force. Neither preferred style of climbing nor the ability level of the climbers could explain these asymmetries. As such, practitioners should consider regularly monitoring unilateral strength, aiming to minimize the likelihood of large bilateral asymmetry occurring.
Oxidative addition of an alkyl halide to form a stable Cu(III) product
Authors: Luo Yongrui , Li Yuli , Wu Jian , Xue Xiao-Song , Hartwig John F. , Shen Qilong
Published: September 2023

The step that cleaves the carbon-halogen bond in copper-catalyzed cross-coupling reactions remains ill defined because of the multiple redox manifolds available to copper and the instability of the high-valent copper product formed. We report the oxidative addition of α-haloacetonitrile to ionic and neutral copper(I) complexes to form previously elusive but here fully characterized copper(III) complexes. The stability of these complexes stems from the strong Cu−CF
3
bond and the high barrier for C(

CF
3

)−C(

CH
2
CN

) bond-forming reductive elimination. The mechanistic studies we performed suggest that oxidative addition to ionic and neutral copper(I) complexes proceeds by means of two different pathways: an S
N
2-type substitution to the ionic complex and a halogen-atom transfer to the neutral complex. We observed a pronounced ligand acceleration of the oxidative addition, which correlates with that observed in the copper-catalyzed couplings of azoles, amines, or alkynes with alkyl electrophiles.
The legacy of Covid denial
The Deadly Rise of Anti-science: A Scientist’s Warning
Peter J. Hotez
Johns Hopkins University Press, 2023. 240 pp.
Authors: Caplan Arthur
Published: September 2023

A physician warns of the broader implications of pandemic backlash
Macrophage superclusters to the rescue
Authors: Louwe Pieter A. , Guilliams Martin
Published: September 2023

Macrophage aggregates step in to capture blood-borne pathogens in the injured liver
Anatomy of a volcanic eruption undersea
Authors: Williams Rebecca , Rowley Pete
Published: September 2023

Submarine flows from the Hunga Tonga–Hunga Ha‘apai eruption decimated seafloor cables
Embed equity throughout innovation
Authors: Wailoo Keith A. , Dzau Victor J. , Yamamoto Keith R.
Published: September 2023

The social benefit of technologies is frequently unevenly realized across the United States. Rural communities, individuals with disabilities, and historically marginalized groups face out-of-reach costs or lack access to products that meet their needs. Blame is typically placed on complicated regulatory processes or complex delivery systems, but this response neglects the problem that equity is not baked into the nation’s innovation process at any stage. The United States needs to rethink its entire innovation ecosystem to incorporate equity as a foundational guiding principle—from research design and funding requirements to policies and regulations that govern the delivery and oversight of new products to the public.
In Science Journals
Authors: Scanlon Seth Thomas , Smith Keith T. , Yeston Jake , Lavine Marc S. , Lopez Bianca , Malo Courtney , VanHook Annalisa M. , Uzogara Ekeoma , Hurtley Stella M. , Kelly Priscilla N. , Grocholski Brent , Maroso Mattia , Isles Hannah M.
Published: September 2023

Highlights from the
Science
family of journals
Should beetles be named after Adolf Hitler?
Authors: Ortega Rodrigo Pérez
Published: September 2023

Zoologists debate whether—and how—to change scientific names now deemed offensive
An
ex vivo
model of
Toxoplasma
recrudescence reveals developmental plasticity of the bradyzoite stage
Authors: Vizcarra Edward A. , Goerner Amber L. , Ulu Arzu , Hong David D. , Bergersen Kristina V. , Talavera Michael A. , Le Roch Karine , Wilson Emma H. , White Michael W.
Published: September 2023

The recrudescence of
Toxoplasma
cysts is the cause of clinical disease in the immunocompromised. Although
Toxoplasma
has been a useful parasite model for decades because it is relatively easy to genetically modify and culture, attempts to generate and study the recrudescence of tissue cysts have come up short with cell culture-adapted strains generating low numbers of tissue cysts
in vivo
. Taking advantage of a new
ex vivo
model of
Toxoplasma
recrudescence that uses a Type II ME49 strain unadapted to cell culture, we determined the cell biology, gene expression, and host cell dependency that define bradyzoite-cyst reactivation. Bradyzoite infection of fibroblasts and astrocytes produced sequential tachyzoite growth stages with pre-programmed kinetics; thus, an initial fast-growing stage was followed by a slow-growing replicating form.
In vivo
infections demonstrated that only fast growth tachyzoites, and not parasites post-growth shift, led to successful parasite dissemination to the brain and peripheral organs. In astrocytes, cells that reside in the central nervous system (CNS), bradyzoites initiated an additional recrudescent pathway involving brady-brady replication, which is a pathway not observed in fibroblasts. To investigate the molecular basis of growth and cell-dependent reactivation pathways, single-cell mRNA sequencing was performed on recrudescing parasites, revealing distinct gene signatures of these parasite populations and confirming multifunctionality of the original
ex vivo
bradyzoite population. This revised model of
Toxoplasma
recrudescence uncovers previously unknown complexity in the clinically important bradyzoite stage of the parasite, which opens the door to further study these novel developmental features of the
Toxoplasma
intermediate life cycle.

IMPORTANCE

The classical depiction of the
Toxoplasma
lifecycle is bradyzoite excystation conversion to tachyzoites, cell lysis, and immune control, followed by the reestablishment of bradyzoites and cysts. In contrast, we show that tachyzoite growth slows independent of the host immune response at a predictable time point following excystation. Furthermore, we demonstrate a host cell-dependent pathway of continuous amplification of the cyst-forming bradyzoite population. The developmental plasticity of the excysted bradyzoites further underlines the critical role the cyst plays in the flexibility of the lifecycle of this ubiquitous parasite. This revised model of
Toxoplasma
recrudescence uncovers previously unknown complexity in the clinically important bradyzoite stage of the parasite, which opens the door to further study these novel developmental features of the
Toxoplasma
intermediate life cycle.
Complete genome sequence of
Pectobacterium brasiliense
strain 21PCA_AGRO2 with antimicrobial resistance isolated from napa cabbage
Authors: Ahn Sojin , Jhang So Yun , Ahn Eunbyeol , Ryu Sangryeol , Yu Jaewoong
Published: September 2023

We report a complete genome of
Pectobacterium brasiliense
strain 21PCA_AGRO2 isolated from napa cabbage, in which the genome consists of a circular chromosome comprising 4,919,671 bp with 4,399 coding DNA sequences, 22 rRNA genes, 77 tRNA genes, and 9 noncoding RNA genes.
A tool for the cheap and rapid screening of SARS-CoV-2 variants of concern (VoCs) by Sanger sequencing
Authors: Burgos Germán , Ambuludí Andrés ,   USFQ SARS-CoV-2 Consortium, Morales-Jadán Diana , Garcia-Bereguiain Miguel Angel , Muslin Claire , Armijos-Jaramillo Vinicio , Carvajal Mateo , Muñoz Erika , Guevara Rommel , Prado Belén , Marquez Sully , Coloma Josefina , Grunauer Michelle , Trueba Gabriel , Barragán Verónica , Rojas-Silva Patricio , Cárdenas Paúl
Published: September 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that, since March 2020, has been responsible for a global and ongoing pandemic. Its rapid spread over the past nearly 3 years has caused novel variants to arise. To monitor the circulation and emergence of SARS-CoV-2 variants, surveillance systems based on nucleotide mutations are required. In this regard, we searched in the spike, ORF8, and nucleocapsid genes to detect variable sites among SARS-CoV-2 variants. We describe polymorphic genetic regions that enable us to differentiate between the Alpha, Beta, Gamma, Delta, and Omicron variants of concern (VoCs). We found 21 relevant mutations, 13 of which are unique for Omicron lineages BA.1/BA.1.1, BA.2, BA.3, BA.4, and BA.5. This genetic profile enables the discrimination between VoCs using only four reverse transcription PCR fragments and Sanger sequencing, offering a cheaper and faster alternative to whole-genome sequencing for SARS-CoV-2 surveillance.

IMPORTANCE

Our work describes a new (Sanger sequencing-based) screening methodology for SARS-CoV-2, performing PCR amplifications of a few target regions to detect diagnostic mutations between virus variants. Using the methodology developed in this work, we were able to discriminate between the following VoCs: Alpha, Beta, Gamma, Delta, and Omicron (BA.1/BA.1.1, BA.2, BA.3, BA.4, and BA.5). This becomes important, especially in low-income countries where current methodologies like next-generation sequencing have prohibitive costs. Furthermore, rapid detection would allow sanitary authorities to take rapid measures to limit the spread of the virus and therefore reduce the probability of new virus dispersion. With this methodological approach, 13 previously unreported diagnostic mutations among several Omicron lineages were found.
Supplemental Material: Origins and evolution of two types of Late Triassic granitic magmas in the Caolong-Xiangkariwa area of central-eastern Songpan-Ganze terrane, Northern Tibet: Implications for pegmatite lithium mineralization
Authors: Liu Jin-Heng , WANG QIANG , et al.
Published: September 2023

Supplemental figures, analytical methods, analytical data, and supplemental references.
Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study
Authors: Meaidi Amani , Mascolo Annamaria , Sessa Maurizio , Toft-Petersen Anne Pernille , Skals Regitze , Gerds Thomas Alexander , Wessel Skovlund Charlotte , Morch Lina Steinrud , Rossi Francesco , Capuano Annalisa , Lidegaard Oejvind , Torp-Pedersen Christian
Published: September 2023

Objective

To study the influence of concomitant use of hormonal contraception and non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of venous thromboembolism.

Design

Nationwide cohort study.

Setting

Denmark through national registries.

Participants

All 15-49 year old women living in Denmark between 1996 and 2017 with no medical history of any venous or arterial thrombotic event, cancer, thrombophilia, hysterectomy, bilateral oophorectomy, sterilisation, or infertility treatment (n=2 029 065).

Main outcome measure

A first time discharge diagnosis of lower limb deep venous thrombosis or pulmonary embolism.

Results

Among 2.0 million women followed for 21.0 million person years, 8710 venous thromboembolic events occurred. Compared with non-use of NSAIDs, use of NSAIDs was associated with an adjusted incidence rate ratio of venous thromboembolism of 7.2 (95% confidence interval 6.0 to 8.5) in women not using hormonal contraception, 11.0 (9.6 to 12.6) in women using high risk hormonal contraception, 7.9 (5.9 to 10.6) in those using medium risk hormonal contraception, and 4.5 (2.6 to 8.1) in users of low/no risk hormonal contraception. The corresponding numbers of extra venous thromboembolic events per 100 000 women over the first week of NSAID treatment compared with non-use of NSAIDs were 4 (3 to 5) in women not using hormonal contraception, 23 (19 to 27) in women using high risk hormonal contraception, 11 (7 to 15) in those using medium risk hormonal contraception, and 3 (0 to 5) in users of low/no risk hormonal contraception.

Conclusions

NSAID use was positively associated with the development of venous thromboembolism in women of reproductive age. The number of extra venous thromboembolic events with NSAID use compared with non-use was significantly larger with concomitant use of high/medium risk hormonal contraception compared with concomitant use of low/no risk hormonal contraception. Women needing both hormonal contraception and regular use of NSAIDs should be advised accordingly.
Year in review: tips for effective graduate medical education programme leadership and management
Authors: Johnson William Rainey , Barelski Adam M , Blickle John G , Wiseman Melanie L , Hartzell Joshua
Published: September 2023

Programme leaders in graduate medical education (GME) are responsible for the final stage of physician training, guiding the transition from supervised to independent practice. The influence of GME programme leaders extends beyond clinical practice, affecting trainees’ relationship with and attitudes towards the healthcare system, future leadership behaviours, work–life prioritisations and professional identity among others. Given the potential magnitude of GME programme leaders’ impact, both positive and negative, on GME trainees, we reflected on our shared leadership model that developed iteratively as a leadership team. We draw on our experiences to emphasise practical leadership behaviours and provide a summary of our observations, leading to nine recommendations for effective GME programme leadership and associated suggestions for implementation. We divide our recommendations into four leadership recommendations and five management recommendations. Throughout, we highlight the process of developing our shared leadership model, recognising that our process and observations will aid leadership teams in evaluating and, potentially, adapting our recommendations to meet their needs. We anticipate that leaders and leadership teams at every level will find value in our recommendations, even if our intended audience is GME leaders from chief residents to programme directors.
Bedside palliative care and geriatric consultations: adherence rate in hospitalised patients
Authors: Pijls Noor , Joosten Hanneke , Theunissen Maurice , van Leendert Jannic , Courtens Annemie , Magdelijns Fabienne , van den Beuken- van Everdingen Marieke
Published: September 2023

Objectives

This study examined the adherence rate of recommendations of a palliative consultation team (PCT) and a geriatric consultation team (GCT). Secondary aims were to investigate which factors and/or recommendation characteristics influence adherence rates.

Methods

This retrospective cohort study was performed in the Maastricht University Medical Center+ in the Netherlands and included hospitalised patients who received a consultation by the PCT or the GCT. Baseline data on consultations were collected for the total population and for the GCT and PCT separately. The adherence rate of the recommendations was evaluated by checking evidence of implementation. The nature of recommendations given (solicited or unsolicited) was documented per domain (somatic, psychological/cognitive, social, spiritual, functional, and existential). The association with adherence was evaluated for solicited and unsolicited recommendations separately. Exploration of potentially associated factors was performed using OpenEpi.

Results

Overall, 507 consultations of individual patients were performed (n=131) by the GCT and (n=376) by the PCT. Most recommendations given were solicited (865/1201=72%). Over 80% of both solicited and unsolicited recommendations were implemented in the majority of domains. No potentially modifiable factors associated with the adherence of the advices were found.

Conclusions

The overall adherence rate of the GCT and PCT consultations was high. In addition, in certain domains, many recommendations were unsolicited. However, also the majority of these recommendations were implemented.
Fruit anatomy and seedlings of the mistletoePsittacanthus schiedeanus(Loranthaceae)
Authors: Ornelas Juan Francisco , Galicia Sonia , Vásquez-Aguilar Antonio Acini , Vovides Andrew P.
Published: September 2023

Fruits of Psittacanthus (Loranthaceae) mistletoes depend on frugivorous birds for seed dispersal; however, despite the importance of birds in their dispersal and distribution, the external fruit morphology and anatomy and seedling remain poorly studied. Here, we describe the fruit anatomy and seedling of host generalist Psittacanthus schiedeanus (Cham. & Schltdl.) G. Don (Loranthaceae), a mistletoe species occurring from Mexico to Panama. Fully developed unripe fruits and ripe fruits were collected, processed for microphotography, and examined to describe fruit external morphology and anatomy. The following parts were observed in fruits: exocarp, viscin layer, seed coat, and the polycotylous embryo. Longitudinal sections also show the inverted position of the embryo. The fruits of Psittacanthus schiedeanus contain a polycotylous embryo and no endosperm. The absence of endosperm in the mature seed and the massive cotyledons having the storage function for the germinating seedling await further Psittacanthus species comparisons to end the pretending controversy of the polycotylous embryo and between having or not having endosperm in Psittacanthus.
Combined application of organic manure and reduced-rate chemical fertilizer improved growth, nutrient use efficiency, biomass accumulation, and carbon sequestration of Zanthoxylum armatum seedlings
Authors: Saba Tahseen , Saleem Fariha , Liu Wanlin , Wang Jingyan , Hui Wenkai , Nazir Hafsa , Gong Wei
Published: September 2023

The possibility of incorporating organic manure (OM) to reduced rates of chemical fertilizers to augment biomass production and carbon sequestration (Cseq) and the role of nitrogen (N), phosphorus (P), and potassium (K) uptake in vegetation Cseq were investigated through pot experiment with 1-year-old Zanthoxylum armatum seedlings. Seven treatments were designed, including NPK, PK, NP, NK, OM, MNPK (50% NPK + 50% OM), and control (CK, no fertilization). MNPK application improved nutrient uptake of 2.76-fold N, 3.34-fold P, and 2.01-fold K, resulting in the highest biomass production and biomass Cseq (1.65-fold) as compared to CK. Correlation and redundancy analysis revealed that Cseq is significantly associated with biomass production ( r = 0.994) and regulated by N and P uptake. The highest nutrient use efficiency was recorded for N (38.8%), followed by K (21.1%) and P (16.4%) under MNPK application. Therefore, MNPK could be an optimum measure regarding fertilizer saving, biomass production, and attaining C neutrality.
Ab-initio investigation of structural, opto-electronic, and thermodynamic properties of ZnAl2Se4 for photovoltaic applications
Authors: Erum Nazia , Ahmad Javed , Iqbal Muhammad Azhar
Published: September 2023

In this manuscript, the structural, opto-electronic, and thermodynamic properties of ZnAl2Se4 chalcogenide compounds were studied in detail using the full potential linearized augmented plane wave method. The exchange and correlation potentials used in density functional theory were calculated using local density approximation, the generalized gradient approximation (GGA) method, and the modified Becke–Johnson (mBJ) potential using Wien2k code. The obtained results were compared with each other as well as with available experimental data. At ambient conditions, ZnAl2Se4 is a direct wide bandgap (Г–Г) semiconductor with a bandgap of 2.1 and 3.3 eV with GGA and mBJ potentials, respectively. Density of states (DOS; total DOS and Partial Density Of States (PDOS)) and electron density contour plots were in similar accordance with bandgap, showing semiconductive behavior and covalent bonding nature. The optical properties like the real and imaginary parts of the dielectric constant, the energy loss function L( ω), and the conductivity σ( ω) were calculated. Optical aspects show interaction among phonon and electron in terms of long-range and short-range forces. The studied compound is very useful for various linear–nonlinear optical devices, so this compound is very valuable for several linear–nonlinear optical devices. So this manuscript represents a comprehensive approach for calculating the complete set of useful properties of the ZnAl2Se4 compound, which can provide support for understanding various device phenomena such as electrochemical sensing, photovoltaics, and nonvolatile electronic memories.
Photo-response of the $$N=Z$$ nucleus $$^{24}$$Mg
Authors: Deary J. , Scheck M. , Schwengner R. , O’Donnell D. , Bemmerer D. , Beyer R. , Hensel Th. , Junghans A. R. , Kögler T. , Müller S. E. , Römer K. , Schmidt K. , Turkat S. , Urlaß S. , Wagner A. , Bowry M. , Adsley P. , Agar O. , Chapman R. , Crespi F. C. L. , Doherty D. T. , Gayer U. Friman , Herzberg R.-D. , Isaak J. , Janssens R. V. F. , Kröll T. , Löher B. , Nara Singh B. S. , von Neumann-Cosel P. , Pellegri L. , Peters E. E. , Rainovski G. , Savran D. , Smith J. F. , Spieker M. , Thirolf P. G. , Triambak S. , Tornow W. , Venhart M. , Wiedeking M. , Wieland O. , Yates S. W. , Zilges A.
Published: September 2023

The electricE1 and magneticM1 dipole responses of the$$N=Z$$N=Znucleus$$^{24}$$24Mg were investigated in an inelastic photon scattering experiment. The 13.0 MeV electrons, which were used to produce the unpolarised bremsstrahlung in the entrance channel of the$$^{24}$$24Mg($$\gamma ,\gamma ^{\prime }$$γ,γ′) reaction, were delivered by the ELBE accelerator of the Helmholtz-Zentrum Dresden-Rossendorf. The collimated bremsstrahlung photons excited one$$J^{\pi }=1^-$$Jπ=1-, four$$J^{\pi }=1^+$$Jπ=1+, and six$$J^{\pi }=2^+$$Jπ=2+states in$$^{24}$$24Mg. De-excitation$$\gamma $$γrays were detected using the four high-purity germanium detectors of the$$\gamma $$γELBE setup, which is dedicated to nuclear resonance fluorescence experiments. In the energy region up to 13.0 MeV a total$$B(M1)\uparrow = 2.7(3)~\mu _N^2$$B(M1)↑=2.7(3)μN2is observed, but this$$N=Z$$N=Znucleus exhibits only marginalE1 strength of less than$$\sum B(E1)\uparrow \le 0.61 \times 10^{-3}$$∑B(E1)↑≤0.61×10-3 e$$^2 \, $$2fm$$^2$$2. The$$B(\varPi 1, 1^{\pi }_i \rightarrow 2^+_1)/B(\varPi 1, 1^{\pi }_i \rightarrow 0^+_{gs})$$B(Π1,1iπ→21+)/B(Π1,1iπ→0gs+)branching ratios in combination with the expected results from the Alaga rules demonstrate thatKis a good approximative quantum number for$$^{24}$$24Mg. The use of the known$$\rho ^2(E0, 0^+_2 \rightarrow 0^+_{gs})$$ρ2(E0,02+→0gs+)strength and the measured$$B(M1, 1^+ \rightarrow 0^+_2)/B(M1, 1^+ \rightarrow 0^+_{gs})$$B(M1,1+→02+)/B(M1,1+→0gs+)branching ratio of the 10.712 MeV$$1^+$$1+level allows, in a two-state mixing model, an extraction of the difference$$\varDelta \beta _2^2$$Δβ22between the prolate ground-state structure and shape-coexisting superdeformed structure built upon the 6432-keV$$0^+_2$$02+level.
Conserved charges of the Kerr black hole revisited
Authors: Günel Okan , Sarıoğlu Özgür
Published: September 2023

We revisit the Kerr black hole as cast in the Boyer–Lindquist, Kerr–Schild and Weyl canonical coordinates, and calculate its total mass/energy and total angular momentum using linearized gravity along with its background Killing isometries. We argue that the integration of the relevant gravitational flux does not depend on the geometry of the closed and simply connected spatial boundary provided it is also piecewise smooth.
Single photon routing based on the selective coupling of the side-branch in the Plasmonic hybrid nanosystem with dipole–dipole interaction
Authors: Ri Su-Ryon , Ko Myong-Chol , Kim Nam-Chol , Ryom Ju-Song , Kim Chol-Min , Ryom Gwang-Myong
Published: September 2023

We propose a theoretical model for the single photon quantum router that consists of two plasmonic waveguides, one of which is infinite and the other is semi-infinite, coupled to two two-level quantum dots (QDs) with dipole–dipole interaction (DDI). The infinite waveguide, the main branch, couples with both QDs, and the semi-infinite, the side branch, couples with the main branch at the position of one of the QDs. In such a system the incident single photon can also be transferred to the side branch, not only be transmitted or reflected. The results show that the transfer rate mainly depends on the coupling strength between the QDs and the two waveguides, but there exists a certain limit in the increase of the transfer rate. The DDI between the QDs gives a remarkable change to the routing spectra and the routing properties are different according to the position of the side branch. The proposed system is indeed multi-channel single photon quantum router, which has more practical significance than the one-dimensional router and can be employed in multi-user quantum networking.
Fashion Entrepreneurship: Narcissism and Entrepreneurial Intention
Authors: Baldegger Urs , Klösel Kilian
Published: September 2023

Narcissism and entrepreneurship have been little studied in previous research. For the fashion industry, the relevance of narcissism is evident. In Paris, Berlin, and Zurich, students from fashion schools were surveyed about the connection between dual narcissism and entrepreneurial intention. The results indicate that there are strong correlations between narcissistic admiration and entrepreneurial intention; however, no significant correlations were found for the second component of dual narcissism and narcissistic rivalry. The simple research design was followed up with a more complex research design that attempts to answer the question of how narcissistic admiration influences entrepreneurial intention. The results highlight the view that entrepreneurial skills and risk-taking (as one of three factors) of individual entrepreneurial orientation mediate the relationship between narcissism and entrepreneurial intention. Unlike proactivity, innovativeness correlates positively and strongly with narcissistic admiration but has no significant effect on entrepreneurial intention. In the fashion industry, innovativeness can be lived by starting a venture or as an entrepreneurial career in the creative environment of existing fashion companies.
Why Should I Trust Your Code?
Authors: Delignat-Lavaud Antoine , Fournet Cédric , Vaswani Kapil , Clebsch Sylvan , Riechert Maik , Costa Manuel , Russinovich Mark
Published: September 2023

For Confidential Computing to become ubiquitous in the cloud, in the same way that HTTPS became the default for networking, a different, more flexible approach is needed. Although there is no guarantee that every malicious code behavior will be caught upfront, precise auditability can be guaranteed: Anyone who suspects that trust has been broken by a confidential service should be able to audit any part of its attested code base, including all updates, dependencies, policies, and tools. To achieve this, we propose an architecture to track code provenance and to hold code providers accountable. At its core, a new Code Transparency Service (CTS) maintains a public, append-only ledger that records all code deployed for confidential services. Before registering new code, CTS automatically applies policies to enforce code-integrity properties. For example, it can enforce the use of authorized releases of library dependencies and verify that code has been compiled with specific runtime checks and analyzed by specific tools. These upfront checks prevent common supply-chain attacks.
Internodal conduction pathways: revisiting a century-long debate on their existence, morphology, and location in the context of 2023 best science
Authors: Cavero Icilio , Holzgrefe Henry
Published: September 2023

This report reexamines disparate historical views on internodal pathway existence and nature. The conflicting research, ongoing since 1963, regarding these issues, is appraised. The discovery of myocytes anisotropically structured in atrial bundles relaying sinoatrial node (SAN) action potentials (APs) to atrioventricular node (AVN) and atrial wall destinations is emphasized, since it is still a relatively unfamiliar subject in physiology teaching. Modern imaging technologies can now visualize internodal pathways as muscular bundles displaying SAN electrical waves traversing the atrial walls.
p53 Gain-of-Function Mutation Induces Metastasis via BRD4-Dependent CSF-1 Expression
Authors: Efe Gizem , Dunbar Karen J. , Sugiura Kensuke , Cunningham Katherine , Carcamo Saul , Karaiskos Spyros , Tang Qiaosi , Cruz-Acuña Ricardo , Resnick-Silverman Lois , Peura Jessica , Lu Chao , Hasson Dan , Klein-Szanto Andres J. , Taylor Alison M. , Manfredi James J. , Prives Carol , Rustgi Anil K.
Published: September 2023

TP53 mutations are frequent in esophageal squamous cell carcinoma (ESCC) and other SCCs and are associated with a proclivity for metastasis. Here, we report that colony-stimulating factor-1 (CSF-1) expression is upregulated significantly in a p53-R172H–dependent manner in metastatic lung lesions of ESCC. The p53-R172H–dependent CSF-1 signaling, through its cognate receptor CSF-1R, increases tumor cell invasion and lung metastasis, which in turn is mediated in part through Stat3 phosphorylation and epithelial-to-mesenchymal transition (EMT). In Trp53R172H tumor cells, p53 occupies the Csf-1 promoter. The Csf-1 locus is enriched with histone 3 lysine 27 acetylation (H3K27ac), which is likely permissive for fostering an interaction between bromodomain-containing domain 4 (BRD4) and p53-R172H to regulate Csf-1 transcription. Inhibition of BRD4 not only reduces tumor invasion and lung metastasis but also reduces circulating CSF-1 levels. Overall, our results establish a novel p53-R172H–dependent BRD4–CSF-1 axis that promotes ESCC lung metastasis and suggest avenues for therapeutic strategies for this difficult-to-treat disease.

Significance:

The invasion–metastasis cascade is a recalcitrant barrier to effective cancer therapy. We establish that the p53-R172H–dependent BRD4-CSF-1 axis is a mediator of prometastatic properties, correlates with patient survival and tumor stages, and its inhibition significantly reduces tumor cell invasion and lung metastasis. This axis can be exploited for therapeutic advantage.

This article is featured in Selected Articles from This Issue, p. 2489
Supplementary Figure S1 from A Druggable FOXA1-Glucocorticoid Receptor Transcriptional Axis Drives Tumor Growth in a Subset of Non-Small Cell Lung Cancer
Authors: Dorso M. , Patel Payal T. , Pankov Aleksandr , Boyer Jacob A. , Soni Rajesh K. , Del Priore Isabella S. , Hayatt Omar , Kulick Amanda , Hagen Connor J. , de Stanchina Elisa , Junttila Melissa R. , Daemen Anneleen , Friedman Lori S. , Hendrickson Ronald C. , Chandarlapaty Sarat
Published: September 2023

Supplemental figure S1 data panels and legend accompanying main body figure 2. Supplementary Figure S1 shows GR is the top-ranked interacting protein of FOXA1 in FOXA1-dependent NSCLC cell lines models. Additionally, FOXA1-dependent, but not FOXA1-independent NSCLC cells depend on GR for sustained proliferation.
Supplemental Table 3 from A Druggable FOXA1-Glucocorticoid Receptor Transcriptional Axis Drives Tumor Growth in a Subset of Non-Small Cell Lung Cancer
Authors: Dorso M. , Patel Payal T. , Pankov Aleksandr , Boyer Jacob A. , Soni Rajesh K. , Del Priore Isabella S. , Hayatt Omar , Kulick Amanda , Hagen Connor J. , de Stanchina Elisa , Junttila Melissa R. , Daemen Anneleen , Friedman Lori S. , Hendrickson Ronald C. , Chandarlapaty Sarat
Published: September 2023

Shared target genes of FOXA1 and GR in NCI-H441 cells