bluuebunny/crossref_metadata_2025 huggingface dataset:
Cutaneous hypersensitivity to chlorhexidine following facial fat grafting: a delayed intradermal response
Authors: Anderson Brady J , Tanenbaum Zachary G , Michael Alexander , Owen Scott R
Published: July 2024

Chlorhexidine (CHD) is commonly included in surgical antiseptics and can be associated with adverse reactions ranging from contact dermatitis to anaphylaxis. A 32-year-old female presented to the OR for facial fat grafting. Surgical sites were prepped with CHD gluconate or topical iodine. Donor and recipient sites were infiltrated with local anesthetic injection prior to fat harvest and facial injection. Eleven days later, she presented with new painful, pruritic rash over donor sites where CHD had been applied prior to local anesthetic infiltration. Treatment with topical clobetasol and prednisone taper resulted in complete symptom resolution. This patient’s response most likely represented a delayed type IV, T-cell mediated hypersensitivity. CHD is a known trigger of allergic reactions. Infiltration of local anesthetic may introduce skin prep into the subcutaneous tissue akin to intradermal testing. For those with delayed cutaneous reactions, steroids may provide symptomatic relief.
An unusual case of giant jejunal diverticula presenting radiologically as toxic megacolon
Authors: Okoli Fidelis C , Tan Sally , Hakmi Hazim , Forman Jacqueline , Hartendorp Patrick A
Published: July 2024

Jejunal diverticulosis is an uncommon entity of the gastrointestinal tract. It involves the presence of multiple diverticula (pouches) in the jejunal wall. Jejunal diverticulosis is not so common, and the epidemiology is ill defined, but usually, it is known to affect the elderly more. They are considered from a pathophysiological point of view as motility disorders, structural defects, or high intraluminal pressures, with the result of prolapse of the mucosa of the jejunum through weak points of the intestinal wall. It represents a rare entity with different clinical presentations, ranging from being asymptomatic to life-threatening complications such as obstruction, bleeding, or perforation. Treatment depends on the presentation and can be conservative or surgical management.
Dorsal ectopic breast—a cutaneous marker of occult spinal dysraphism
Authors: Ismail Muhammad , Thet Myat Soe , Khan Kalim Ullah , Ullah Nusrat
Published: July 2024

Ectopic breasts represent uncommon medical anomalies characterized by the presence of additional breasts situated outside the typical milk line. In this case report, we present a case encompassing dorsal ectopic breasts accompanied by three nipples. A 14-year-old teen girl presented with a significant dorsal mass, exhibiting no clinical manifestations except mild pain and a sense of heaviness. She underwent investigations, and a magnetic resonance imaging scan revealed a large, inadequately encapsulated congenital mass with a fatty composition, alongside intraspinal epidural engagement and a bony structure bridging the spinous processes from the C6 to the T3 vertebral bodies. She subsequently underwent excision of the entire mass. The histopathological analysis identified the presence of a mammary hamartoma. Follow-up at 2 weeks postoperatively showed that there were no further complications. Dorsal ectopic breast necessitates careful and comprehensive evaluation to either confirm or exclude the presence of occult spinal dysraphism prior to intervention to avoid complications.
Establishment of a national travel medicine vaccination network to assess reactogenicity of new and rarely used vaccines: a TropNet study
Authors: Köpke Clara , Rothe Camilla , Zeder Andreas , Boecken Gerhard , Feldt Torsten , Janke Christian , Jordan Sabine , Löbermann Micha , Müller Andreas , Orth Hans-Martin , Prüfer-Krämer Luise Marie , Schäfer Johannes , Slesak Günther , Stich August , Bélard Sabine , Thul Nico , Becker Sören L , Schneitler Sophie ,   TravVacNet-Group
Published: July 2024

The successful establishment and roll-out of a post-licensing surveillance network to assess the reactogenicity of rarely used new vaccines by anonymous data donation to rapidly share early experiences from daily practice.
Potential therapeutic strategies for MASH: from preclinical to clinical development
Authors: Xie Zhifu , Li Yufeng , Cheng Long , Huang Yidan , Rao Wanglin , Shi Honglu , Li Jingya
Published: July 2024

Current treatment paradigms for metabolic dysfunction-associated steatohepatitis (MASH) are based primarily on dietary restrictions and the use of existing drugs, including anti-diabetic and anti-obesity medications. Given the limited number of approved drugs specifically for MASH, recent efforts have focused on promising strategies that specifically target hepatic lipid metabolism, inflammation, fibrosis, or a combination of these processes. In this review, we examined the pathophysiology underlying the development of MASH in relation to recent advances in effective MASH therapy. Particularly, we analyzed the effects of lipogenesis inhibitors, nuclear receptor agonists, glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists, fibroblast growth factor mimetics, and combinatorial therapeutic approaches. We summarize these targets along with their preclinical and clinical candidates with the ultimate goal of optimizing the therapeutic prospects for MASH.
Delayed Diagnosis of a Ligamentous Lisfranc Injury on a Bomber Task Force Member
Authors: Anderson Kevin D , Harper Hollan , Ayers Sarah K
Published: July 2024

The tarsometatarsal joint, or Lisfranc joint, is an extremely important anatomical structure and injury to it has been shown to cause long-term disabling ramifications. With a wide spectrum of injury involvement, from fracture dislocations to sprains, it is important to establish a diagnosis early to guide management. Although the more extreme higher energy fracture dislocations are more widely studied, there remains a paucity of literature on lower energy purely ligamentous injuries, especially among military service members.1 The deployed setting provides an extra layer of complexity in determining a musculoskeletal injury etiology for the provider, especially in resource-limited areas. When a high level of suspicion for Lisfranc injury exists based upon clinical presentation and in the setting of negative X-rays, more prudence should be placed on additional workup. This will guide decision-making for possible expedited stateside return for the patient and better odds of follow-up care. The following case demonstrates a unique scenario of an undiagnosed, purely ligamentous Lisfranc tear in a 23-year-old woman in a deployed environment with late presentation to an orthopedic surgeon stateside. Furthermore, emphasis is placed on factors that led to her delayed diagnosis and how advocating for advanced imaging modalities up-front can expedite care.
The Role of Student Coping Strategies on Success in the Command Actions Course: A Special Operations Selection Course of the Brazilian Army
Authors: Tolentino Filipe de Carvalho , Ferreira Daniele Bittencourt
Published: July 2024

Introduction

Army Command Action units in Brazil are recognized for their operational effectiveness, operating in hostile scenarios. However, these operations are extremely stressful, requiring specific stress-coping skills. The objective of this study was to identify the profile of stress-coping strategies of military personnel enrolled in the Command Actions Course (CAC) and their relationship with completion of the course.

Materials and Methods

A prospective cohort study was carried out with 87 military personnel from the CAC class of 2022. Data were collected on personal characteristics, coping strategies, and stress levels, among other variables. Specific instruments were used to assess coping (Brief-COPE), stress (DASS-21), social support (MOSS), and sociodemographic variables (own instrument) to evaluate the relationship between coping with stress and course completion. Descriptive analyses were performed (central tendency and dispersion measures), and overall survival analysis was performed using the log-rank test for comparison (P < .05). Cox regression was used for multiple analyses considering a statistical significance of 5%.

Results

A total of 31% of the participants completed the course. The profile of graduates is mainly composed of young people with higher education, single status, and White. Certain coping strategies such as Active Coping (hazard ratio (HR) = 1.48; 95% CI, 1.25-1.75) as well as high stress levels (HR = 1.07; 95% CI, 1.02-1.11) were associated with disengagement, while the Humor-based coping strategy reduced the chance of disengagement by 15% (HR = 0.85; 95% CI, 0.74-0.98).

Conclusions

This study highlights the importance of investigation using coping strategies in the military context as a useful tool in coping with stress in the CAC.
Associations Between PTSD Features and Firearm Ownership and Storage: Results From the PRImary Care Screening Methods (PRISM) Study
Authors: Bauder Christina Rose , Rooney Emily A , Hay Jarrod M , Long Cameron M , Bryan Craig J
Published: July 2024

Introduction

Veterans and active duty service members are significantly more likely to die by suicide using firearms compared to the general population. Not-secure firearm storage (e.g., keeping guns loaded/in an unlocked location) is associated with greater risk for suicide and a third of veteran firearm owners store at least 1 personal firearm unsecured. Veterans and active duty service members are also significantly more likely to be diagnosed with posttraumatic stress disorder (PTSD) than the general population. Symptoms of PTSD are divided into 4 criteria: reexperiencing, avoidance, negative affect, and hyperarousal. Research has suggested that endorsement of hyperarousal symptoms is positively associated with unsecure firearm storage and that avoidance symptoms might be negatively associated with unsecure storage practices. The present study examined the relationship between self-reported firearm ownership and storage practices among each item from the Primary Care PTSD Screening for DSM-IV-TR (PC-PTSD-IV) to explore associations between PTSD features and firearm ownership and storage.

Materials and Methods

Participants were recruited from primary care clinics across 5 military installations in the United States as part of a larger study (Mage = 45.4, SD = 16.9). Among participants (n = 2,685), most of our sample identified as male (51.3%) and white (67.3%) with 61.6% currently serving in the military, 16.8% retirees, and 21.6% family members. PTSD symptoms were assessed using the PC-PTSD-IV and a quarter met the clinical threshold for PTSD. Binomial and multinomial logistic regression analyses were used.

Results

Among completed responses, 989 (38.1%) people reported owning guns; among gun owners, 386 (39.0%) reported that they were loaded, and 352 (35.6%) reported they were loaded and unlocked. Endorsement of specific items on the PC-PTSD-IV, including those specific to hyperarousal and avoidance, was not significantly associated with storing firearms loaded and/or in nonsecure locations when controlling for military service. Non-responses to items around firearm storage practices were significantly associated with those individuals meeting the clinical threshold for PTSD according to the PC-PTSD-IV and participants currently serving had higher odds of storing at least 1 personal firearm loaded and both loaded and unlocked.

Conclusions

Results from our study highlight similarities and departures from the previous literature on the connection between PTSD and non-secure firearm storage practices. Further research may examine (1) the relation between PTSD symptoms and firearm storage between active duty service members, retirees, and family members and (2) whether non-response to items regarding firearm ownership is systematic.
Histoplasmosis in non-immunosuppressed patients from an endemic area in Northeastern Brazil
Authors: Leitão Terezinha do Menino Jesus Silva , Rodrigues Nina Brunet Saraiva , Farias Luís Arthur Brasil Gadelha , Henn Guilherme Alves de Lima , Mota Rosa Salani , Costa Rafael de Sousa , Damasceno Lisandra Serra
Published: July 2024

Differently from immunocompromised patients, very little information is available in the literature regarding the clinical presentation, epidemiology, and outcomes of histoplasmosis in non-immunosuppressed individuals living in endemic areas. This retrospective case series study was carried out by reviewing the medical records of non-immunocompromised patients with histoplasmosis, residents in a hyperendemic area in northeastern Brazil, between 2011 and 2022. Thirty HIV-negative patients were identified with histoplasmosis, and 19 cases met the inclusion criteria: three had acute, five subacute and one chronic pulmonary forms; two with mediastinal picture and eight had disseminated disease (two with severe symptoms). The median age of our sample was 32.7 years old [interquartile range: 24–45]. Most of the patients were male (male-to-female ratio = 15:4) and resided in the state capital (n = 9). The majority had a previous history of exposure to well-known risk factors for Histoplasma infection. Pulmonary nodules were observed in all subacute form, two patients (acute and subacute forms) were initially treated empirically for pulmonary tuberculosis; one death was registered in the subacute form. The chronic pulmonary form of histoplasmosis was diagnosed in one patient only after the symptoms persisted despite specific treatment. The primary clinical manifestations of the moderate form of DH were enlarged lymph nodes, with histopathology being the main diagnostic method. The cases were detected as isolated occurrences and not as an outbreak, suggesting that exposure to Histoplasma can be more widespread than presumed. Despite the self-limiting nature of the disease, death can occur even in previously heathy patients.
Determining the viewing angle from TeV light curve of GRB 221009A
Authors: Zhou Lin , Zou Yuan-Chuan
Published: July 2024

Gamma-ray bursts (GRBs) are among the most powerful explosive events in the Universe. LHAASO recently observed the most luminous one: GRB 221009A, and unveiled its TeV light curve. The light curve exhibits a distinct jet break at around 670 s, enabling the derivation of the viewing angle based on the smoothness of the jet break. We constructed two models with or without considering the high-latitude radiation, where the viewing angle was treated as a free parameter, to fit the TeV light curve. The viewing angles obtained were 9.4 $\times 10^{-4}$ and 5.9 $\times 10^{-3}$ rad, respectively. These values closely resemble an on-axis scenario, given the opening angle is 1.4 $\times 10^{-2}$ rad.
Isochrone fitting of the open cluster M67 in the era of Gaia and improved model physics
Authors: Reyes Claudia , Stello Dennis , Hon Marc , Trampedach Regner , Sandquist Eric , Pinsonneault Marc H
Published: July 2024

The Gaia mission has provided highly accurate observations that have significantly reduced the scatter in the colour–magnitude diagrams of open clusters. As a result of the improved isochrone sequence of the open cluster M67, we have created new stellar models that avoid commonly used simplifications in 1D stellar modelling, such as mass-independent core overshooting and a constant mixing length parameter. This has enabled us to deliver a precise isochrone specifically designed for M67, available for download. We follow a commonly used qualitative approach to adjust the input physics to match the well-defined colour–magnitude sequence, and we test the model-predicted masses against a known eclipsing binary system at the main sequence turnoff of the cluster. Despite using improvements in photometry and stellar physics we cannot match the masses of both binary components with the same theoretical isochrone. A $\chi ^{2}$-based isochrone fitting approach using our preferred input physics results in a cluster age of $3.95^{+ 0.16}_{- 0.15}$ Gyr.
Kinematic morphology of low-mass galaxies in IllustrisTNG
Authors: Zeng Guangquan , Wang Lan , Gao Liang , Yang Hang
Published: July 2024

The origin of diverse kinematic morphologies observed in low-mass galaxies is unclear. In this study, we investigate the kinematic morphologies of central galaxies with stellar mass $10^{8.5-9.0}{\rm M}_{\odot }$ at $z=0$ in the TNG50-1 cosmological simulation. The majority of the low-mass galaxies in TNG50-1 are dispersion-dominated, consistent with observations. By tracing the evolutionary histories of simulated low-mass galaxies, we find that while most stars form in rotating cold gas discs, the orientation of the star-forming discs relative to the galaxies may evolve with cosmic time. If the cold gas disc remains aligning with the galaxy during its evolution, stars formed at different times share the same rotational direction, leading to a rotation-dominated system. On the contrary, frequent misalignment of cold gas disc would result in a dispersion-dominated system. In addition, we also find that the two-body scattering can have a non-negligible numerical heating effect on the simulated galaxy morphology, especially at central regions of galaxies and for relatively low-mass galaxies. By comparing results of simulations with different resolutions, our results suggest that the simulated morphology of galaxies is roughly reliable when their number of stellar particles exceeds about $10^{4}$, and bulge morphology of galaxies can not be resolved robustly at the resolution level of TNG50-1.
A study of two FRBs with low polarization fractions localized with the MeerTRAP transient buffer system
Authors: Rajwade K M , Driessen L N , Barr E D , Pastor-Marazuela I , Berezina M , Jankowski F , Muller A , Kahinga L , Stappers B W , Bezuidenhout M C , Caleb M , Deller A , Fong W , Gordon A , Kramer M , Malenta M , Morello V , Prochaska J X , Sanidas S , Surnis M , Tejos N , Wagner S
Published: July 2024

Localization of fast radio bursts (FRBs) to arcsecond and subarcsecond precision maximizes their potential as cosmological probes. To that end, FRB detection instruments are deploying triggered complex-voltage capture systems to localize FRBs, identify their host galaxy, and measure a redshift. Here, we report the discovery and localization of two FRBs (20220717A and 20220905A) that were captured by the transient buffer system deployed by the MeerTRAP instrument at the MeerKAT telescope in South Africa. We were able to localize the FRBs to precision of $\sim$1 arcsecond that allowed us to unambiguously identify the host galaxy for FRB 20220717A (posterior probability $\sim$0.97). FRB 20220905A lies in a crowded region of the sky with a tentative identification of a host galaxy but the faintness and the difficulty in obtaining an optical spectrum preclude a conclusive association. The bursts show low linear polarization fractions (10–17 per cent) that conform to the large diversity in the polarization fraction observed in apparently non-repeating FRBs akin to single pulses from neutron stars. We also show that the host galaxy of FRB 20220717A contributes roughly 15 per cent of the total dispersion measure (DM), indicating that it is located in a plasma-rich part of the host galaxy which can explain the large rotation measure. The scattering in FRB 20220717A can be mostly attributed to the host galaxy and the intervening medium and is consistent with what is seen in the wider FRB population.
Eccentricity dynamics of wide binaries – II. The effect of stellar encounters and constraints on formation channels
Authors: Hamilton Chris , Modak Shaunak
Published: July 2024

Gaia wide stellar binaries (separations $\sim 10^3{\!-\!}10^{4.5}$ au) are observed to have a superthermal eccentricity distribution function (DF), well-fit by $P(e) \propto e^\alpha$ with $\alpha \sim 1.2$. In a previous paper, we proved that this DF cannot have been produced by Galactic tidal torques starting from any realistic DF that was not already superthermal. Here, we consider the other major dynamical effect on wide binaries: encounters with passing stars. We derive and solve the Fokker–Planck equation governing the evolution of binaries in semimajor axis and eccentricity under many weak, impulsive, penetrative stellar encounters. We show analytically that these encounters drive the eccentricity DF towards thermal on the same time-scale as they drive the semimajor axes a towards disruption, $t_\mathrm{dis}\sim 4\, \mathrm{Gyr}\, (a/10^4\, \mathrm{AU})^{-1}$. We conclude that the observed superthermal DF must derive from an even more superthermal (i.e. higher $\alpha$) birth distribution. This requirement places strong constraints on the dominant binary formation channels. A testable prediction of our theory is that $\alpha$ should be a monotonically decreasing function of binary age.
The influence of baryons on low-mass haloes
Authors: Zheng Haonan , Bose Sownak , Frenk Carlos S , Gao Liang , Jenkins Adrian , Liao Shihong , Springel Volker , Wang Jie , White Simon D M
Published: July 2024

The Voids-within-Voids-within-Voids project used dark-matter-only (DMO) simulations to study the abundance and structure of dark matter (DM) haloes over the full mass range populated in the standard Lambda cold dark matter cosmology. Here, we explore how baryonic effects modify these results for $z=0$ halo masses in the range $10^4$–$10^7~\mathrm{M_\odot }$, below the threshold for galaxy formation. Our main study focuses on three simulations from identical initial conditions at $z=127$, one following DMO, one including non-radiative gas, and one additionally including the baryonic physics relevant in this halo mass range (cooling and photoheating). In the non-radiative simulation, above $10^{5.5}~\mathrm{M_\odot }$, halo abundance and internal structure are very similar to the DMO simulation, and the baryon to DM ratio is everywhere close to the cosmic value. At lower mass, this ratio drops and haloes are less concentrated and less massive in the non-radiative case. Test simulations at higher resolution show this to be mainly a resolution effect; the expected drop in baryon content due to residual pressure effects only becomes substantial for $z=0$ haloes below ${\sim}10^{2.7}~\mathrm{M_\odot }$. However, gas is heated by reionization at $z=6$ in our ‘full physics’ run, and this results in almost complete expulsion of gas from all haloes in our simulated mass range. This suppresses the halo mass function by ${\sim}30{{\ \rm per\ cent}}$, lowers halo concentration, and consequently weakens the DM annihilation signal by ${\sim}40{-}60{{\ \rm per\ cent}}$.
Nietzsche’s Genealogical Perfectionism
Authors: Lorenzini Daniele
Published: July 2024

I argue that Nietzsche’s Genealogy of Morality can be productively read as perfectionist in Emerson’s sense. After reconstructing the debate on Nietzsche’s perfectionism, I problematize the literature’s almost exclusive focus on Schopenhauer as Educator at the expense of the Genealogy, which has caused scholars to construe Nietzsche’s perfectionism in merely individualistic terms. By contrast, I show that the Genealogy can be interpreted as a perfectionist endeavor, at the heart of which lies the first-person plural: the “we.” I thereby emphasize the relevance of “we-making” for a novel reading of Nietzsche’s perfectionism—what I call his genealogical perfectionism. I conclude that the analysis of the genealogical dimension of Nietzsche’s perfectionism provides us with much-needed resources to construe it in nonindividualistic terms.
Unlocking precision gene therapy: harnessing AAV tropism with nanobody swapping at capsid hotspots
Authors: Hoffmann Mareike D , Gallant Joseph P , LeBeau Aaron M , Schmidt Daniel
Published: July 2024

Adeno-associated virus (AAV) has been remarkably successful in the clinic, but its broad tropism is a practical limitation of precision gene therapy. A promising path to engineer AAV tropism is the addition of binding domains to the AAV capsid that recognize cell surface markers present on a targeted cell type. We have recently identified two previously unexplored capsid regions near the 2/5-fold wall and 5-fold pore of the AAV capsid that are amenable to insertion of larger protein domains, including nanobodies. Here, we demonstrate that these hotspots facilitate AAV tropism switching through simple nanobody replacement without extensive optimization in both VP1 and VP2. Our data suggest that engineering VP2 is the preferred path for maintaining both virus production yield and infectivity. We demonstrate highly specific targeting of human cancer cells expressing fibroblast activating protein (FAP). Furthermore, we found that the combination of FAP nanobody insertion plus ablation of the heparin binding domain can reduce off-target infection to a minimum, while maintaining a strong infection of FAP receptor-positive cells. Taken together, our study shows that nanobody swapping at multiple capsid locations is a viable strategy for nanobody-directed cell-specific AAV targeting.
Exploring complex and integrated information during sleep
Authors: Onoda Keiichi , Akama Hiroyuki
Published: July 2024

The Integrated Information Theory is a theoretical framework that aims to elucidate the nature of consciousness by postulating that it emerges from the integration of information within a system, and that the degree of consciousness depends on the extent of information integration within the system. When consciousness is lost, the core complex of consciousness proposed by the Integrated Information Theory disintegrates, and Φ measures, which reflect the level of integrated information, are expected to diminish. This study examined the predictions of the Integrated Information Theory using the global brain network acquired via functional magnetic resonance imaging during various tasks and sleep. We discovered that the complex located within the frontoparietal network remained constant regardless of task content, while the regional distribution of the complex collapsed in the initial stages of sleep. Furthermore, Φ measures decreased as sleep progressed under limited analysis conditions. These findings align with predictions made by the Integrated Information Theory and support its postulates.
Emerging innovations in electrically powered artificial muscle fibers
Authors: Lang Tianhong , Yang Lixue , Yang Shiju , Sheng Nan , Zhang Yiyao , Song Xiaofei , Guo Yang , Fang Shaoli , Mu Jiuke , Baughman Ray H
Published: July 2024

This review systematically explores the inherent structural advantages of fiber over conventional film or bulk forms for artificial muscles, emphasizing their enhanced mechanical properties and actuation, scalability, and design flexibility. Distinctive merits of electrically powered artificial muscle fiber actuation mechanisms, including electrothermal, electrochemical and dielectric actuation, are highlighted, particularly for their operational efficiency, precise control capabilities, miniaturizability and seamless integration with electronic components. A comprehensive overview of significant research driving performance enhancements in artificial muscle fibers through materials and structural innovations is provided, alongside a discussion of the diverse design methodologies that have emerged in this field. A detailed comparative assessment evaluates the performance metrics, advantages and manufacturing complexities of each actuation mechanism, underscoring their suitability for various applications. Concluding with a strategic outlook, the review identifies key challenges and proposes targeted research directions to advance and refine artificial muscle fiber technologies.
Shaping the Future: Proposed Bills to Regulate New and Emerging Tobacco and Nicotine Products in Latin America and the Caribbean Amidst Public Health Concerns and Industry Interests
Authors: Severini Luciana , de Figueiredo Beatriz Albuquerque , Severini Gianella , Tran Brian , Sebrié Ernesto M , Crosbie Eric
Published: July 2024

Introduction

To examine legislative efforts to regulate new and emerging tobacco and nicotine products (NETNPs) in Latin America and the Caribbean (LAC) between 2017 and 2022.

Aims and Methods

Analysis of online national legislation databases to track NETNP bills using standard snowball search methods.

Results

Bills were identified in 15 out of the 33 LAC countries, accounting for a total of 91 bills targeting NETNPs. Mexico had the highest number (n = 38) of bills, followed by Brazil (n = 16), Argentina (n = 10), Colombia (n = 8), and Chile (n = 5). The remaining countries introduced two or fewer NETNP bills. Among the identified 91 bills, the majority (n = 60) addressed both electronic cigarettes and heated tobacco products (HTPs), almost one-third of bills (n = 29) applied only to electronic cigarettes, and only two focused solely on HTPs. Six of the fifteen countries with identified bills, enacted one NETNP law including Barbados, Bolivia, Costa Rica, Guyana, Mexico, and Panama. Since 2019, there has been a steady increase in the amount of NETNP bills introduced in LAC. In 2017 and 2018, 10 NETNP bills were introduced each year followed by 23 NETNP bills introduced in each 2019 and 2020, 19 in 2021, and 16 by August 2022.

Conclusions

The substantial increase in the number of NETNP bills introduced since 2019 indicates the growing importance of regulating NETNPs in LAC. As NETNPs continue to evolve and grow it is important to continue monitoring and evaluating tobacco and nicotine regulatory initiatives while also staying ahead of the evolving market of NETNPs.

Implications

Previous studies have analyzed the regulatory environment of NETNPs but it is less known about legislative and regulatory efforts and attempts. This is the first known study to analyze legislative bills to regulate NETNPs in Latin America and the Caribbean (LAC). The substantial increase in the number of NETNP bills introduced in LAC since 2019 indicates the growing importance of regulating NETNPs in LAC. As NETNPs continue to evolve and grow it is important to continue monitoring and evaluating tobacco and nicotine regulatory initiatives while also staying ahead of the evolving market of NETNPs.
FDA approval summary: fam-trastuzumab deruxtecan-nxki for unresectable or metastatic non-small cell lung cancer with activating HER2 mutations
Authors: Mehta Gautam U , Vellanki Paz J , Ren Yi , Amatya Anup K , Mishra-Kalyani Pallavi S , Pan Lili , Zirkelbach Jeanne F , Pan Yuzhuo , Liu Jiang , Aungst Stephanie L , Miller Claudia P , Shah Mirat , Rahman Nam Atiqur , Theoret Marc , Kluetz Paul , Pazdur Richard , Beaver Julia A , Singh Harpreet
Published: July 2024

On August 11, 2022, FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd, ENHERTU, Daiichi Sankyo) for adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating human epidermal growth factor receptor 2 (HER2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. The approval was based on a prespecified interim analysis of DESTINY-Lung02 (Study U206), a multi-center, randomized, dose-optimization trial in patients with NSCLC harboring activating HER2-mutations. At the approved dose of 5.4 mg/kg given intravenously every 3 weeks, the overall response rate (ORR) was 58% (95% confidence interval [CI]: 43, 71). The median duration of response was 8.7 months (95% CI: 7.1, not estimable). These results were consistent with response rates observed at the 6.4 mg/kg dose level. The most common (≥ 20%) adverse reactions were nausea, constipation, decreased appetite, vomiting, fatigue, and alopecia. The rate of interstitial lung disease (ILD) or pneumonitis was 6% at the 5.4 mg/kg dose level and 14% at the 6.4 mg/kg dose level. In the setting of similar efficacy and reduced toxicity, approval was granted for the 5.4 mg/kg dose level. The applicant conducted a randomized, dose-optimization study with guidance from the FDA Oncology Center of Excellence’s Project Optimus. This is the first approval of a targeted therapy for HER2-mutated NSCLC.
Prediction of moderate and severe toxicities of chemotherapy in older patients with cancer: a propensity weighted analysis of ELCAPA cohort
Authors: Benderra Marc-Antoine , Paillaud Elena , Broussier Amaury , Layese Richard , Tapia Claudia M , Mebarki Soraya , Boudou-Rouquette Pascale , Laurent Marie , Piero Monica , Rollot-Trad Florence , Gligorov Joseph , Caillet Philippe , Canoui-Poitrïne Florence
Published: July 2024

Background

Currently available predictive models for chemotherapy-related toxicity are not sufficiently discriminative in older patients with cancer and do not consider moderate toxicities. The purpose of this study was to identify factors associated with moderate and severe chemotherapy toxicities in older patients with cancer.

Materials and methods

Patients aged 70+ recruited in the prospective ELCAPA cohort were analyzed. A total of 837 patients with data on toxicities had received chemotherapy without other systemic treatment and were included between 2015 and 2022. To adjust for any imbalances in the distribution of covariates between patients receiving single-agent chemotherapy vs combination chemotherapy, we applied overlap weighting (a propensity-score-based technique). We used multinomial logistic regression.

Results

Median (interquartile range) age was 81 (77-84). Forty-one percent experienced moderate toxicity, and 33% experienced severe toxicity. Hematologic toxicities accounted for 53% of severe toxicities and 66% of moderate toxicities. Age <80 years, cancer type, metastatic status, Eastern Cooperative Oncology Group performance status (ECOG-PS) >1, no cognitive impairment were associated with combination chemotherapy decision. In a univariate analysis with overlap weighting, no factors were associated with moderate toxicity. Hemoglobin < 10 g/dL and a CIRS-G score >12 were associated with severe toxicity. In a multivariate analysis, only hemoglobin < 10 g/dL was independently associated with severe toxicity, adjusted OR 2.96 (95% CI, 1.20-7.29).

Conclusion

By addressing indication bias for combination chemotherapy decision, only anemia and not cancer type, combination chemotherapy was predicting for severe chemotherapy-related toxicity in older patients with cancer. We did not find any predictors of moderate chemotherapy-related toxicity.
Improving the care of children with autism and related neurodevelopmental disorders in emergency department settings: Understanding the knowledge-to-practice continuum of emergency department providers
Authors: Niro Julia , Zubairi Mohammad S , Leung James S
Published: July 2024

Objectives

Emergency department (ED) healthcare providers (HCPs) frequently describe a lack of knowledge in caring for children with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). Our primary objective is to explore gaps in training and clinical exposure reported by ED HCPs caring for children with ASD/NDD.

Methods

A two-phase, mixed-methods cross-sectional study was conducted. In phase 1, an interprofessional sample of tertiary care paediatric ED HCPs (physicians, nurses, social workers, and child life specialists) were surveyed about their experiences and perceived gaps in managing children with ASD/NDD. These responses informed phase 2, where six semi-structured interviews were conducted. Interview transcripts were analyzed to determine themes around the discomfort of ED HCPs caring for children with ASD/NDD.

Results

The majority, 54/78 (69%) of eligible staff completed the survey. A minority (42.5%) of HCPs had mandatory training on ASD/NDD, and 80% would value continuing education. Some ED HCPs (41.2%) had previous personal or professional experiences with children with ASD/NDD that facilitated deeper empathy and awareness of system challenges. Interviews revealed four themes of ED HCP discomfort with this population: 1) added considerations of interacting with children and families with ASD/NDD; 2) the ED as a single touch point in complex and limited healthcare systems; 3) recognizing comfort in discomfort; and 4) the need to implement practical interventions to improve care.

Conclusions

ED HCPs are motivated to improve care for children with ASD/NDD. Alongside broader systems interventions, future educational interventions can narrow ED HCP gaps identified through this work.
How bodily perception parallels distal perception
Authors: Gray Richard
Published: July 2024

Bodily perception is standardly contrasted with distal perception. In this paper, I argue that the standard view overlooks a significant respect in which bodily perception parallels distal perception. The parallel is motivated by a comparison between two cross-modal illusions. The ventriloquism effect manifests cross-modal relations between the distal senses of vision and audition and multi-sensory experiences jointly constituted by vision and audition. Thermal referral is a laboratory induced illusion that involves the bodily sensory systems underlying the perception of pressure and heat. I argue that thermal referral indicates the presence of cross-modal relations and multi-sensory experiences of a type sufficiently similar to those manifested by the ventriloquism effect to suggest that pressure and thermal perception parallel vision and audition at the level of bodily perception.
A contribution to the mathematical theory of diffraction. Part II: Recovering the far-field asymptotics of the quarter-plane problem
Authors: Assier R C , Shanin A V , Korolkov A I
Published: July 2024

We apply the stationary phase method developed in Assier, Shanin and Korolkov, QJMAM, 76 (2022) to the problem of wave diffraction by a quarter-plane subjected to Dirichlet boundary conditions. The wave field is written as a double Fourier transform of an unknown spectral function. We make use of the analytical continuation results of Assier and Shanin, QJMAM, 72 (2018) to uncover the singularity structure of this spectral function. This allows us to provide a closed-form far-field asymptotic expansion of the field by estimating the double Fourier integral near some special points of the spectral function. All the known results on the far-field asymptotics of the quarter-plane problem are recovered, and new mathematical expressions are derived for the secondary diffracted waves in the plane of the scatterer.
The forearm elevation–compression test: a novel test for carpal tunnel syndrome
Authors: Hawkes C H , Cutter G
Published: July 2024

Background

As the time available to spend with patients decreases, a rapid test for bedside diagnosis of carpal tunnel syndrome (CTS) could be useful.

Design and Methods

We describe the forearm elevation–compression test (FECT) in this context. The FECT was assessed in 40 patients with clinically suspected CTS and compared to Tinel’s and Phalen’s signs. Routine electromyography and nerve conduction tests (EMG/NCT) were performed in all cases. In addition, 85 healthy controls were examined by FECT and compared to the patient group.

Results

All three provocative tests, particularly FECT, were frequently positive in suspected CTS. Neurophysiological tests were normal in 5 of 40 cases of clinically suspected CTS, and the FECT was positive in all of these suggesting a positive predictive value of 87.5% if one accepts EMG/NCT as the reference. Amongst the healthy controls, 18 of 85 (21.2%) were positive on the FECT suggestive of a high false-positive rate or subclinical disease.

Conclusion

It is proposed that the FECT is a useful addition to the clinical examination of suspected CTS. Although the positive rate may be falsely elevated, this is offset by restricting the latency for tingling onset to 10 s or less (FECT2).
Are lessons being learnt from the replication crisis or will the revolution devour its children? Open Q science from the editor's perspective
Authors: Hüttel Silke , Hess Sebastian
Published: July 2024

The scientific production system is crucial in how global challenges are addressed. However, scholars have recently begun to voice concerns about structural inefficiencies within the system, as highlighted, for example, by the replication crisis, the p-value debate and various forms of publication bias. Most suggested remedies tend to address only partial aspects of the system's inefficiencies, but there is currently no unifying agenda in favour of an overall transformation of the system. Based on a critical review of the current scientific system and an exploratory pilot study about the state of student training, we argue that a unifying agenda is urgently needed, particularly given the emergence of artificial intelligence (AI) as a tool in scientific writing and the research discovery process. Without appropriate responses from academia, this trend may even compound current issues around credibility due to limited replicability and ritual-based statistical practice while amplifying all forms of existing biases. Naïve openness in the science system alone is unlikely to lead to major improvements. We contribute to the debate and call for a system reform by identifying key elements in the definition of transformation pathways towards open, democratic and conscious learning, teaching, reviewing and publishing supported by openly maintained AI tools. Roles and incentives within the review process will have to adapt and be strengthened in relation to those that apply to authors. Scientists will have to write less, learn differently and review more in the future, but need to be trained better in and for AI even today.
The relationship between obesity and patient-reported outcome measures in people with polymyalgia rheumatica
Authors: Scott Ian C , Bajpai Ram , Hider Samantha L , Helliwell Toby , Mallen Christian D , Muller Sara
Published: July 2024

Objective

To examine the association between obesity and patient-reported outcome measures (PROMs) in a primary care-based cohort of people with PMR.

Methods

The PMR Cohort Study recruited people with incident PMR from 382 general practices. Self-completed questionnaires (0, 12, 24 months) captured a range of PROMs for pain, stiffness, anxiety, depression, fatigue, function and quality of life, alongside data on BMI. People were categorized as underweight/normal weight (BMI < 25kg/m2), overweight (25–29.99 kg/m2) or obese (≥30 kg/m2). Piecewise, multilevel, linear mixed-effects regression models examined relationships between BMI categories and PROMs over time, adjusting for confounding variables. Chi-squared tests examined the relationship between obesity and glucocorticoid persistence.

Results

644 people with PMR were included. At baseline, 33.9% were normal/underweight, 40.6% overweight and 25.5% obese. Compared with normal/underweight people, those with obesity had significantly worse scores for the following: pain and stiffness at 12 months; fatigue at 12 and 24 months; depression at baseline; physical function at all time points; and quality of life at baseline and 12 months. They also had significantly smaller improvements in stiffness (1.13 units on an 11-point numeric rating scale; P = 0.001) and physical function (0.14 units measured using the modified Health Assessment Questionnaire; P = 0.025) between 0 and 12 months. BMI categories did not relate to persistent glucocorticoid use at 12 months (P = 0.110) or 24 months (P = 0.166).

Conclusion

Obesity associates with poorer outcomes for a range of PROMs in people with PMR. Consideration should be given to providing weight management support to people with PMR and obesity.
Enhanced Bayesian RFI mitigation and transient flagging using likelihood reweighting
Authors: Anstey Dominic , Leeney Samuel A K
Published: July 2024

Contamination by radio frequency interference (RFI) is a ubiquitous challenge for radio astronomy. In particular, transient RFI is difficult to detect and avoid, especially in large data sets with many time bins. In this work, we present a Bayesian methodology for time-dependent, transient anomaly mitigation performed jointly with model fitting. The computation time for correcting transient anomalies in this manner in time-separated data sets grows proportionally with the number of time bins. We demonstrate that utilizing likelihood reweighting can allow our Bayesian anomaly mitigation method to be performed with a computation time close to independent of the number of time bins. In particular, we identify a factor of 44 improvement in computation time for a test case with 2000 time bins. We also demonstrate how this method enables the flagging threshold to be fit as a free parameter, fully automating the mitigation process. We find that this threshold fitting also prevents overcorrecting of the data in the case of wide priors. Finally, we investigate the potential of the methodology as a transient detector. We demonstrate that the method is able to reliably flag an individual anomalous data point out of 302 000 provided the Signal to Noise Ratio is $\ge\!{10}$.
Impact of conventional and biological disease-modifying anti-rheumatic drugs on arterial lesions in Takayasu arteritis
Authors: Bletry Diego , Meyblum Louis , Desseaux Kristell , Vautier Mathieu , Chiche Laurent , Le Joncour Alexandre , Redheuil Alban , Roux Charles , Cacoub Patrice , Gaudric Julien , Biard Lucie , Saadoun David
Published: July 2024

Background

The definition of Takayasu arteritis (TAK) remission and disease activity is still unclear. Vascular imaging is an essential tool for following-up patients. Herein, we aimed to compare the evolution of vascular lesions (i.e. vessel wall thickening and stenosis) under conventional cDMARDs relatively to biological DMARDs (bDMARDs) in TAK patients followed with the same CT angiography modalities.

Method

We compared 75 lines of therapy in TAK patients who received cDMARDs (n = 40 lines) and bDMARDs (n = 35 lines) using CT angiography. We established 1–3 main target vessels with vessel wall thickening and/or stenosis. Every targeted vessel had its thickness and its lumen diameter measured at the initiation of immunosuppressive treatment and at 12 months.

Results

We observed an overall reduction in arterial wall thickness in 73% of cases and 31% had >25% relative decrease in the wall thickness. Using a linear mixed effects model, first-line immunosuppressive therapy (P = 0.012) and bDMARDs relatively to cDMARDs (P = 0.026) were independently associated with vessel wall thickness reduction in TAK. Thirty-eight percent of the stenotic vessels had a > 25% relative increase in lumen diameter under immunosuppressive therapy. The relative increase >25% in lumen diameter was noted in 56% vs 17% with bDMARDs compared with cDMARDs.

Conclusion

Immunosuppressive treatments can reduce arterial wall thickness and widen lumen diameter in TAK. bDMARDs seem to be more effective than cDMARDs to improve arterial lesions in TAK.