bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction in procedure duration when utilizing active esophageal cooling in patients with persistent atrial fibrillation - update from a large hospital registry
Authors: Cooper J , Joseph C , Willms D , Ruppert A , Francisco G , Kulstad E , Athill C
Published: May 2023

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, And Blood Institute of the National Institutes of Health.

Background

During left atrial ablation, lesions may be placed on the posterior wall of the left atrium. Due to the anatomical proximity of the left atrium to the esophagus, there is significant risk for thermal esophageal injury and potentially atrio-esophageal fistula. Ablation of persistent atrial fibrillation (AF) may involve even more lesion placement, and increased risk and procedure time as a result. In order to protect the esophagus, there are two main methods of esophageal protection, luminal esophageal temperature (LET) monitoring and active esophageal cooling. Recent studies have compared LET monitoring to active cooling and found a reduction in overall esophageal injury when utilizing active cooling, in addition to a reduction in procedure time. However, these studies generally included all patients with AF regardless of which type.

Purpose

We aimed to investigate the association between procedure duration and esophageal protection method among persistent AF patients.

Methods

In this study, we obtained data from an existing clinician-maintained hospital registry. We collected procedure durations from patients with persistent AF undergoing left atrial ablation from January 2018 to May 2022. All patients that met these criteria were included.

Results

Data were analyzed from 161 patients. Active esophageal cooling was utilized in 90 procedures, while LET monitoring was utilized in 71 procedures. The median procedure duration in the actively cooled group was 146 minutes with an interquartile range (IQR) of 58. The median procedure duration in the LET monitored group was 173 minutes with an IQR of 60. This represents a median difference of 27 minutes or 16% of the total procedure duration (p<.001)

Conclusions

The use of active esophageal cooling is associated with a significant reduction in overall procedure time among patients with persistent atrial fibrillation.
3D imaging assistance impact on atrial fibrillation cryoablation efficiency, a method validation study
Authors: Solana Munoz J , Teres C , Luca A , Herrera-Siklody C , Leupi H , Domenichini G , Pascale P , Pruvot E , Le Bloa M
Published: May 2023

Funding Acknowledgements

Type of funding sources: Other. Main funding source(s): CGRA: CARD; CGRB: 31’297

Background

Pulmonary vein isolation (PVI) by cryoballoon ablation is a well-known therapy for the treatment of atrial fibrillation (AF). Current 3D-navigation technologies usually used with RF ablation allow for a drastic reduction of intra-procedural X-ray exposure and imaging aided/guided methods allow for better anatomical characterization improving acute and long-term procedural results. 3D imaging fusion on real-time fluoroscopy is a well-known technology but the incremental value of 3D imaging fusion as a guiding tool on AF cryoballoon ablation therapy has not been studied yet.

Purpose

To increase procedural efficiency by integration of 3D imaging guidance in conventional cryoballoon PVI.

Methods

Using semi-automatic segmentation (Alphenix, Canon Medical Systems Corporation) obtained from pre-procedural cardiac computed tomography (CT); two anatomic volumes were fused on the real-time fluoroscopy display: left atrium (LA), including pulmonary veins (PV) and spine with proximal rib section (most radio-opaque body part in the thoracic area). The merging was performed by 3D registration of the bone segment with fluoroscopic acquisitions in three standard positions (AP, LAO, RAO), acquired at the beginning of the procedure. To standardize treatment workflow, the study was restricted to patients with paroxysmal atrial fibrillation.

Results

Twenty patients were included in the study: 10 in the control group (conventional fluoroscopy based cryoballoon ablation), and 10 in the 3D assisted group. Mean age was 59±15 SD years for the conventional group and 61.3±15.1 SD years for the 3D group with an 80% male population, in both groups. Acute PVI was achieved in all 20 patients. A decrease of both procedure time 86.8±16.1 SD in the control group Vs. 78.4±15.32 SD in the 3D group, and left sided dwelling time 69.7±14.31 SD in the control group Vs. 63.9±13.96 SD in the 3D group, although this trend did not reach statistical significance, while radiation time and cryo application time remained similar.

Conclusions

3D imaging integration is feasible and safe and allows for an exact PV anatomy depiction on fluoroscopy. The assistance workflow might help increase AF cryoablation efficiency and safety (lower left sided dwelling time). Further research is needed to evaluate the incremental value of 3D imaging to assist fluoroscopy-based cryoballoon ablation. This could also impact long-term results since 3D Imaging assistance could reduce the likeability of missing intermediate PVs during AF ablation procedures.
Peak frequency mapping to differentiate near-field from far-field electrograms for ventricular tachycardia ablation: initial results
Authors: Yamaguchi T , Merino Llorens J L , Kim S , Martinez Cossiani M , San Roman M , Relan J , Castrejon Castrejon S , Jauregui Abularach M , Guido Lopez L E , Merino D , Carton Sanchez A J , Escobar Cervantes C , Martinez Maldonado M E , Ugueto Rodrigo C , De La Vieja Alarcon J J
Published: May 2023

Funding Acknowledgements

Type of funding sources: Private company. Main funding source(s): Abbott Laboratories

Background

Ablation of ventricular tachycardia (VT) in patients with structural heart disease is challenging. Localization of the critical isthmus of conduction may be difficult because is commonly located within low voltage (LV) areas where far-field (FF) and near-field (NF) electrograms (EGMs) may be present and merged. The peak frequency (PF) associated with bipolar EGMs is a novel parameter which may serve to distinguish NF from FF EGM components. The potential value of PF to identify the critical isthmus of conduction in this setting has never been evaluated.

Purpose

To compare the ability of LV vs. LVHF to discriminate the VT termination region

Methods

Bipolar voltage and activation maps were generated with a 16-pole grid catheter (Advisor HD Grid) during VT. Peak frequency maps were retrospectively computed. VTs were included if acute termination could be achieved through application of a focal RF lesions set restricted to a boundary <1.5cm diameter. The ventricular LV mapped surface was sub-regioned into the termination (T-ZONE) and non-termination (NT-ZONE) zones. The T-ZONE surface was centered about the site of termination and was allowed to extend to a rectangular kernel >0.5cm and <1.5cm across perpendicular axes, with the NT-ZONE encompassing the remainder of the mapped surface area (SA). Sensitivity (SE) and specificity (SP) of discrimination of the T-ZONE vs. NT-ZONE was measured according to the %T-ZONE vs. %NT-ZONE SA occupied at LV thresholds ranging from 0.1-1.0mV in increments of 0.1mV (Panel E). In addition to LV, LVHF at peak frequency cutoffs of 200Hz (LVHF200), 250Hz (LVHF250), 300Hz (LVHF300) and 400Hz (LVHF400) were also assessed for T-ZONE discrimination.

Results

8 patients with sustained monomorphic VT and structural heart disease (ischemic and non-ischemic) were enrolled. All of them had VT terminated with limited ablation by focal ablation at a discrete region. All areas of VT termination were located in a LV and high PF zone (figure 1). The best area under the curve to identify them was using the 250 Hz cuttoff (AUC 0.91) which was also better that using omnipolar optimized voltage alone (AUC 0.84) (Figure 2).

Conclusion

PF mapping apparently identifies slow conduction isthmus and provides complementary information to bipolar voltage mapping which can be displayed with emphasis on the electranatomical map.
Global Regularity of Skew Mean Curvature Flow for Small Data in d ≥ 4 Dimensions
Authors: Huang Jiaxi , Li Ze , Tataru Daniel
Published: May 2023

The skew mean curvature flow is an evolution equation for a $d$ dimensional manifold immersed into $\mathbb {R}^{d+2}$, and which moves along the binormal direction with a speed proportional to its mean curvature. In this article, we prove small data global regularity in low-regularity Sobolev spaces for the skew mean curvature flow in dimensions $d\geq 4$. This extends the local well-posedness result in [7].
Susceptibility to SARS-CoV-2 Infection and Immune Responses to COVID-19 Vaccination Among Recipients of Solid Organ Transplants
Authors: Subramanian Vijay
Published: May 2023

Solid organ transplant recipients (SOTRs) are at high risk for infections including SARS-CoV-2, primarily due to use of immunosuppressive therapies that prevent organ rejection. Furthermore, these immunosuppressants are typically associated with suboptimal responses to vaccination. While COVID-19 vaccines have reduced the risk of COVID-19–related morbidity and mortality in SOTRs, breakthrough infection rates and death remain higher in this population compared with immunocompetent individuals. Approaches to enhancing response in SOTRs, such as through administration of additional doses and heterologous vaccination, have resulted in increased seroresponse and antibody levels. In this article, safety and immunogenicity of mRNA COVID-19 vaccines in SOTRs are explored by dose. Key considerations for clinical practice and the current vaccine recommendations for SOTRs are discussed within the context of the dynamic COVID-19 vaccination guideline landscape. A thorough understanding of these topics is essential for determining public health and vaccination strategies to help protect immunocompromised populations, including SOTRs.
Interpreting cancer incidence trends: challenges due to the COVID-19 pandemic
Authors: Mariotto Angela B , Feuer Eric J , Howlader Nadia , Chen Huann-Sheng , Negoita Serban , Cronin Kathleen A
Published: May 2023

The considerable deficit in cancer diagnoses in 2020 due to COVID-19 pandemic disruptions in health care can pose challenges in the estimation and interpretation of long-term cancer trends. Using Surveillance, Epidemiology, and End Results (SEER) (2000-2020) data, we demonstrate that inclusion of the 2020 incidence rates in joinpoint models to estimate trends can result in a poorer fit to the data and less accurate or less precise trend estimates, providing challenges in the interpretation of the estimates as a cancer control measure. To measure the decline in 2020 relative to 2019 cancer incidence rates, we used the percent change of rates in 2020 compared with 2019. Overall, SEER cancer incidence rates dropped approximately 10% in 2020, but for thyroid cancer the decrease was as large as 18% after adjusting for reporting delay. The 2020 SEER incidence data are available in all SEER released products, except for joinpoint estimates of trends and lifetime risk of developing cancer.
Cecal bascule in pregnancy: a case report and review of the literature
Authors: Kreinces Jason , Robbins Alicia I , Kim Daniel E
Published: May 2023

A 36-year-old female at 36 weeks’ gestation presented with right upper quadrant abdominal pain. She had no prior surgeries. Her pregnancy had been uncomplicated up until her presentation. Abdominal ultrasound was negative for cholecystitis or cholelithiasis, and the appendix was not visualized. During the second day of her hospital course, an abdominal magnetic resonance imaging (MRI) was performed revealing dilated small intestine with air-fluid levels and an inverted-appearing, prominent cecum. She was urgently taken to the operating room for cesarean section followed by abdominal exploration. After delivery of the child, a cecal bascule was found, with a severely distended cecum. To our knowledge, this is the first report of a cecal bascule diagnosed by MRI, and the first diagnosis of cecal bascule in a pregnant patient requiring surgical intervention. We discuss the pathophysiology, diagnosis and treatment of cecal bascule and review the current literature of reported cases.
(038) Adherence Patterns And Costs For Flibanserin: A Single Practice Experience
Authors: Myers M C , Marantidis J , Mora B , Sussman R D , Rubin R S
Published: May 2023

Introduction

Flibanserin is a partial serotonin agonist/antagonist and has been approved for use in premenopausal females with hypoactive sexual desire disorder (HSDD). This medication has been used off-label in males and postmenopausal females in the management of low libido. There is a paucity of data on prescribing patterns for both on and off-label use.

Objective

This study aims to evaluate costs and refill patterns for flibanserin and to determine if adherence was affected by insurance coverage or off-label use.

Methods

This was a retrospective review of online pharmacy records for patients from one sexual medicine practice that were prescribed flibanserin. De-identified patient information was collected and included age, gender, menopause status, refill information, and out-of-pocket cost. All prescriptions for premenopausal and perimenopausal females met criteria for on-label use and all prescriptions for men and postmenopausal females were considered off-label.

Results

Data was available from 109 patients. Forty-nine premenopausal/perimenopausal women were included in the on-label group and 60 patients were assigned to the off-label group as they were males (n=31) or postmenopausal females (n=29). Twelve percent of patients never filled their prescription, 28% filled it once, and 60% filled it ≥2 times. There was no significant difference in the percentage of patients with 0, 1 and ≥2 prescriptions filled between the on and off-label groups (12%, 24%, 63% vs. 12%, 32%, 57%). Out-of-pocket cost of flibanserin without insurance coverage was $99 for a 30-day supply or $199 for a 90-day supply. Twenty-one percent of patients had insurance coverage and their cost was $0 or $20 for a 30-day supply. The average out-of-pocket cost was $67 per 30-day supply (SD=$34). There was no significant difference in the percentage of patients with 0, 1 and ≥2 prescriptions filled between patients with and without insurance coverage (0%, 24%, 76% vs. 3%, 34%, 64%). The percentage of patients with insurance coverage did not significantly differ between those with on and off-label prescriptions (25% vs. 19%).

Conclusions

This study is the first to explore medication adherence and cost of flibanserin. Sixty percent of patients filled ≥2 prescriptions and refill rates were not affected by off-label use or insurance coverage. Only 21% of patients had insurance coverage for the medication. The limitations of the study include a small sample size from one clinic. The results of this study will help clinicians to recognize costs and adherence with on and off-label use of flibanserin.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Sprout Pharmaceuticals, Absorption Pharmaceuticals.
(039) Vaginal Orgasms: Really exists?
Authors: Dominguez-bali A , Hassan Z , Baqer A , Sharma R , Dominguez-bali C , Marquez L
Published: May 2023

Introduction

In 1948 Alfred Kinsey’s investigation of female and male sexuality found that 80% of women reached orgasm mainly through non-coital sexual experiences, such as oral and physical manipulation of the genitals or through sex toys. After that many peer-reviewed studies confirmed these data as well as in our practice. However, the question remains; what happened with the other 20% that reached orgasm through vaginal penetration.

Objective

To describe the epidemiological sexual characteristics of the 20% of women who reached orgasm mainly through vaginal penetration.

Methods

Over 3000 sexual histories were done in our medical center and were used to collect data regarding the reasons for the orgasm obtained through vaginal penetration. This study includes retrospective and prospective questionnaires applied to all patients seen in our centers.

Results

The epidemiological sexual characteristic of this specific group of women are: - 75% have had only one sexual partner in their lives - 20% of them have had two sexual partners in their life and - 5% of them have more than two. It has been very scantly found that women with a history of multiple sexual partners enjoy sexual penetration. The orgasmic response resulting from coital sex was more persistent and presently found while the number of sexual partners was less. Increased orgasmic responsiveness was also present when the initiation of the sexual activity with the partner was earlier in life.

Conclusions

When the sexual development of a woman is allowed to mature in the presence of a lifelong partner. Their response to penetrative vaginal stimuli is better and the obtention of sexual pleasure and orgasm reinforce this response that persists throughout life and is more attainable over any other form of vaginal stimulation.

Disclosure

No
(069) Vaginal Lubrication: Equally Important for Orgasm in Premenopausal and Postmenopausal Women?
Authors: Dubinskaya A , Dallas K , Harper L , Shoureshi P , Krychman M , Eilber K
Published: May 2023

Introduction

The female sexual response cycle is complex with interconnected domains. Studies have shown that vaginal lubrication is affected by age and hormonal changes; however, the relationship between lubrication and orgasm has not been well described in premenopausal women, women who are postpartum, and postmenopausal women.

Objective

The objective of this study is to evaluate the relationship between vaginal lubrication and orgasm among premenopausal, postpartum, and postmenopausal women.

Methods

A post-market analysis was performed of all women who had utilized the sexual wellness application Rosy between February 2022 and November 2022. Application users complete the Female Sexual Function Index (FSFI) short form (6-item) upon initial use of the application. We utilized multivariable linear regression models to determine significant effects between lubrication score and orgasm scores score controlling for whether the patient was on birth control, postpartum, or menopausal.

Results

We reviewed a large database of 30,358 women from across the United States. Among these, 2,599 women were menopausal, 2, 011 were premenopausal women, and 795 were postpartum. The mean lubrication scores on FSFI -6 were: menopausal = 1.93, premenopausal = 2.68, postpartum = 2.73. Mean scores for orgasm were 2.2, 2.62, 2.31 respectively. Premenopausal women had higher overall scores on FSFI- 6, with orgasm scores improving with age. Higher scores in lubrication domain had less impact on orgasm domain in pre-menopausal women compared to post-menopausal women (p=0.04). No correlation between improvement in lubrication and orgasm noted among post-partum women when compared to post-menopausal women (p=0.87).

Conclusions

Lubrication has a higher impact on orgasm among post-menopausal women compared to pre-menopausal women and not correlated with orgasmic function among women in the post-partum period. These findings enhance our knowledge and refine current management of anorgasmia.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Abbvie, Coloplast, Rosy.
(081) The Psychosocial Barriers Associated with Vulvodynia and Vestibulodynia
Authors: Niedenfuehr J , King L , Edwards M
Published: May 2023

Introduction

At least 8-16% of people with a vulva are affected by generalized vulvodynia and vestibulodynia. These conditions impact interpersonal relationships, individual behaviors, and the psychological health of couples and individuals. Recent reviews suggest there is no comprehensive understanding on how psychosocial factors impact patients with these conditions.

Objective

The aim of this review is to analyze, evaluate, and synthesize vulvodynia and vestibulodynia research regarding psychosocial barriers present in the literature from 2012-2022 in the United States and Canada. In addition to psychosocial barriers, structural determinants and environmental barriers were included to comprehensively evaluate all aspects.

Methods

We searched PubMed, CINAHL, Embase, Web of Science, APA PsychInfo, and Academic Search Premier to retrieve eligible journal articles in March of 2022. A search string of key terms and subject headings including Medical Subject Headings were used systematically to search these databases. The reference list was reviewed with an additional reviewer to reduce bias.

Results

A total of 671 papers were discovered and narrowed down to 74 papers that explored at least one psychosocial barrier for patients or providers in the United States and Canada. The findings of the literature search revealed the various psychosocial barriers that patients commonly face such as pain, anxiety, depression, catastrophization, fear, lack of self-efficacy, low desire and arousal, negative body image, stigma, distress, post-traumatic stress disorder (PTSD), child maltreatment and abuse, mistrust, invalidation and isolation, low levels of self-compassion, negative partner support, low relationship satisfaction, lack of physical affection, emotional regulation, and avoidance and lack of approach goals. In addition to psychosocial barriers, structural determinants, and environmental barriers, such as delayed diagnosis, low health literacy, cost, transportation, and racial disparities also adversely impacted individuals with vulvodynia.

Conclusions

This review serves to educate and inform providers and physicians of the unique barriers that patients experience when navigating health care services and treatments for vulvodynia and vestibulodynia. More research is needed to understand and better educate patients and providers on vulvar pain conditions to improve outcomes.

Disclosure

No
(110) Characterizing Sexuality and Assessing Predictors of Sexual Satisfaction in Patients with Multiple Myeloma
Authors: Henkelman M , Toivonen K , Tay J , Beattie S , Walker L
Published: May 2023

Introduction

There is a paucity of literature documenting cancer-related sexual concerns among patients with multiple myeloma (MM). Despite profound sexual changes being reported in other types of hematological cancer (i.e., lymphoma, leukemia), all types of hematological cancer patients tend to be grouped together, potentially overlooking the unique concerns of patients with MM.

Objective

This study is the first to characterize sexuality uniquely in the MM population, and to examine predictors of sexual satisfaction for MM, comparatively with participants with other hematological cancer types.

Methods

We performed a mixed modality self-report survey of patients with hematological cancer, recruiting both in-person and online. Men and women with MM (N=89) and other hematological cancers (N=84) participated in our survey. The survey included demographics and health information, as well as several quantitative sexuality measures including sexual distress, sexual function, sexual flexibility, sexual interest, sexual communication, and sexual satisfaction.

Results

MM survivors exhibited poor sexual function but low sexual distress, and endorsed mid-high scores on measures of sexual interest, sexual flexibility, sexual communication, and sexual satisfaction. Results indicate that for MM and other hematological cancer survivors, lower sexual distress and higher sexual communication were associated with higher sexual satisfaction (b = .428, p < .001; b = -.299, p = .001) while sexual flexibility, sexual interest, and sexual function did not explain significant variance in sexual satisfaction. Thematic analysis on open-ended questions indicates that potentially unique to MM, consequences of bone disease (i.e., bone pain, bone fracture, and spinal cord compression) affected sexual expression and resulted in reduced mobility impacting sexual activity, as well as painful sexual experiences, or anxiety relating to sex.

Conclusions

This study supported the need for sexual health interventions for those diagnosed with MM. Further, it demonstrated that sexual interventions that are used for other hematological cancer patients may be similarly effective for those with MM. Special consideration regarding the impact of bone disease on sexual expression in MM patients should be taken.

Disclosure

No
(127) Dyspareunia as a Symptom of Urinary Tract Infection
Authors: Dominguez-Bali A , Sharma R , Baqer A , Hassan Z , Dominguez-Bali C , Marquez L
Published: May 2023

Introduction

In 2010, our center presented to the annual congress for the society for the scientific study of sex, research related to the sexual attitude and behavior of Hispanic women in our area. We interviewed and assessed 3,000 patients and discovered in the analysis of the data that dyspareunia was associated with 1,333 patients between the ages of 17-72, co-occurring with urinary tract infection (UTI). In approximately 83.7% of total UTI cases, patients were also positive for dyspareunia. We have reviewed the literature and corroborate that dyspareunia has never been described as part of the symptomatology of UTI. Since then, we have continued to confirm these findings through the follow-up of thousands of women over the last 12 years.

Objective

This study demonstrates how dyspareunia is one of the most important symptoms of UTI, along with the clinical symptoms of pollakiuria, dysuria, urodynia, nocturia, lower abdominal pain, headache, and fever.

Methods

We used an initial review in the area of sexuality in which we found a correlation between dyspareunia and UTI. Since 2010, we have followed thousands of women seen in our centers regarding the presence of dyspareunia as a symptom of UTI.

Results

In 83% of the UTI cases studied over the years, dyspareunia was endorsed as a symptom. Of these, approximately 94% of cases responded positively to treatment with antibiotics. Additionally, the dyspareunia gradually disappeared with the treatment of the UTI. We also found that 80% of women of reproductive age presenting with complaints of dyspareunia had an undiagnosed UTI. During the perimenopausal and postmenopausal years, dyspareunia is more often associated with genitourinary syndrome of menopause than UTI.

Conclusions

Dyspareunia has been described as one of the symptoms of interstitial cystitis but has never been implicated as a significant symptom of regular uncomplicated or complicated UTI. We have found that this symptom is extremely important as part of the symptomatology of the UTI, frequently found along with the classical symptoms of UTI. Why has something so clear, so frequently present, never been described? The answer is simple, physicians and patients do not talk about sex, despite dyspareunia being more a clinical symptom than a sexual one. Medical schools and residency programs in all areas, especially in obstetrics and gynecology, urology, and psychiatry, have neglected the education of physicians-in-training in this area of extreme importance for human health. In conclusion, this is proof of the unscientific way in which medicine has sometimes been influenced by religion, culture, and social norms.

Disclosure

No
MIZU-KUSSEI1 (MIZ1) and GNOM/MIZ2 control not only positive hydrotropism but also phototropism in Arabidopsis roots
Authors: Pang Lei , Kobayashi Akie , Atsumi Yuka , Miyazawa Yutaka , Fujii Nobuharu , Dietrich Daniela , Bennett Malcolm J , Takahashi Hideyuki
Published: May 2023

In response to unilateral blue light illumination, roots of some plant species such as Arabidopsis thaliana exhibit negative phototropism (bending away from light), which is important for light avoidance in nature. MIZU-KUSSEI1 (MIZ1) and GNOM/MIZ2 are essential for positive hydrotropism (i.e. in the presence of a moisture gradient, root bending towards greater water availability). Intriguingly, mutations in these genes also cause a substantial reduction in phototropism. Here, we examined whether the same tissue-specific sites of expression required for MIZ1- and GNOM/MIZ2-regulated hydrotropism in Arabidopsis roots are also required for phototropism. The attenuated phototropic response of miz1 roots was completely restored when a functional MIZ1–green fluorescent protein (GFP) fusion was expressed in the cortex of the root elongation zone but not in other tissues such as root cap, meristem, epidermis, or endodermis. The hydrotropic defect and reduced phototropism of miz2 roots were restored by GNOM/MIZ2 expression in either the epidermis, cortex, or stele, but not in the root cap or endodermis. Thus, the sites in root tissues that are involved in the regulation of MIZ1- and GNOM/MIZ2-dependent hydrotropism also regulate phototropism. These results suggest that MIZ1- and GNOM/MIZ2-mediated pathways are, at least in part, shared by hydrotropic and phototropic responses in Arabidopsis roots.
Association of Traumatic Brain Injury and Glioblastoma Multiforme: A Case Series
Authors: An Joseph , Freeman Emily , Stewart Ian J , Dore Michael
Published: May 2023

Glioblastoma multiforme (GBM) is an aggressive variant of central nervous system gliomas that carries a dismal prognosis. Although GBM is the most frequently occurring and malignant type of glioma accounting for more than 60% of all brain tumors in adults, its overall incidence is rare, occurring at a rate of 3.21 per 100,000 persons. Little is known about the etiology of GBM, but one proposed theory is that GBM pathogenesis may be linked to a chronic inflammatory course initiated by traumatic injury to the brain. Limited case reports have suggested an association between GBMs and traumatic brain injury (TBI), but larger case–control and epidemiologic studies have been inconclusive. We present three service members (two active duty and one retired) who developed GBM near the original site of prior head trauma. Each service member’s military occupation was in the special operations community and shared a common theme of TBI following head trauma/injury. The current research on the association between TBI and GBM is limited and conflicting, predominantly due to the low incidence of the disease in the general population. Evidence has indicated that TBI should be considered a chronic disease with long-term health impacts, including long-term disability, dementia, epilepsy, mental health conditions, and cardiovascular diseases. With the addition of our patients, as well as a recently published study proposing a molecular association between trauma and GBM, further research is needed to better understand the potential relationship.
On the growth of supermassive black holes formed from the gravitational collapse of fermionic dark matter cores
Authors: Argüelles C R , Boshkayev K , Krut A , Nurbakhyt G , Rueda J A , Ruffini R , Uribe-Suárez J D , Yunis R
Published: May 2023

Observations support the idea that supermassive black holes (SMBHs) power the emission at the centre of active galaxies. However, contrary to stellar-mass BHs, there is a poor understanding of their origin and physical formation channel. In this article, we propose a new process of SMBH formation in the early Universe that is not associated with baryonic matter (massive stars) or primordial cosmology. In this novel approach, SMBH seeds originate from the gravitational collapse of fermionic dense dark matter (DM) cores that arise at the centre of DM haloes as they form. We show that such a DM formation channel can occur before star formation, leading to heavier BH seeds than standard baryonic channels. The SMBH seeds subsequently grow by accretion. We compute the evolution of the mass and angular momentum of the BH using a geodesic general relativistic disc accretion model. We show that these SMBH seeds grow to ∼109–$10^{10} \, \mathrm{M}_\odot$ in the first Gyr of the lifetime of the Universe without invoking unrealistic (or fine-tuned) accretion rates.
Simulating the diversity of shapes of the Lyman-α line
Authors: Blaizot Jérémy , Garel Thibault , Verhamme Anne , Katz Harley , Kimm Taysun , Michel-Dansac Léo , Mitchell Peter D , Rosdahl Joakim , Trebitsch Maxime
Published: May 2023

The Ly α line is a powerful probe of distant galaxies, which contains information about inflowing/outflowing gas through which Ly α photons scatter. To develop our understanding of this probe, we post-process a zoom-in radiation-hydrodynamics simulation of a low-mass (Mstar ∼ 109 M⊙) galaxy to construct 22 500 mock spectra in 300 directions from z = 3 to 4. Remarkably, we show that one galaxy can reproduce the variety of a large sample of spectroscopically observed Ly α line profiles. While most mock spectra exhibit double-peak profiles with a dominant red peak, their shapes cover a large parameter space in terms of peak velocities, peak separation, and flux ratio. This diversity originates from radiative transfer effects at interstellar medium and circum-galactic medium (CGM) scales, and depends on galaxy inclination and evolutionary phase. Red-dominated lines preferentially arise in face-on directions during post-starburst outflows and are bright. Conversely, accretion phases usually yield symmetric double peaks in the edge-on direction and are fainter. While resonant scattering effects at <0.2 × Rvir are responsible for the broadening and velocity shift of the red peak, the extended CGM acts as a screen and impacts the observed peak separation. The ability of simulations to reproduce observed Ly α profiles and link their properties with galaxy physical parameters offers new perspectives to use Ly α to constrain the mechanisms that regulate galaxy formation and evolution. Notably, our study implies that deeper Ly α surveys may unveil a new population of blue-dominated lines tracing inflowing gas.
Distinguishing magnetized disc winds from turbulent viscosity through substructure morphology in planet-forming discs
Authors: Wu Yinhao , Chen Yi-Xian , Jiang Haochang , Dong Ruobing , Macías Enrique , Lin Min-Kai , Rosotti Giovanni P , Elbakyan Vardan
Published: May 2023

The traditional paradigm of viscosity-dominated evolution of protoplanetary discs has been recently challenged by existence of magnetized disc winds. However, distinguishing wind-driven and turbulence-driven accretion through observations has been difficult. In this study, we present a novel approach to identifying their separate contribution to angular momentum transport by studying the gap and ring morphology of planet-forming discs in the ALMA continuum. We model the gap-opening process of planets in discs with both viscous evolution and wind-driven accretion by 2D multifluid hydrodynamical simulations. Our results show that gap-opening planets in wind-driven accreting discs generate characteristic dust substructures that differ from those in purely viscous discs. Specifically, we demonstrate that discs where wind-driven accretion dominates the production of substructures exhibit significant asymmetries. Based on the diverse outputs of mock images in the ALMA continuum, we roughly divide the planet-induced features into four regimes (moderate-viscosity dominated, moderate-wind dominated, strong-wind dominated, and inviscid). The classification of these regimes sets up a potential method to constrain the strength of magnetized disc wind and viscosity based on the observed gap and ring morphology. We discuss the asymmetry feature in our mock images and its potential manifestation in ALMA observations.
Targeted tissue delivery of RNA therapeutics using antibody–oligonucleotide conjugates (AOCs)
Authors: Malecova Barbora , Burke Rob S , Cochran Michael , Hood Michael D , Johns Rachel , Kovach Philip R , Doppalapudi Venkata R , Erdogan Gulin , Arias J Danny , Darimont Beatrice , Miller Christopher D , Huang Hanhua , Geall Andrew , Younis Husam S , Levin Arthur A
Published: May 2023

Although targeting TfR1 to deliver oligonucleotides to skeletal muscle has been demonstrated in rodents, effectiveness and pharmacokinetic/pharmacodynamic (PKPD) properties remained unknown in higher species. We developed antibody–oligonucleotide conjugates (AOCs) towards mice or monkeys utilizing anti-TfR1 monoclonal antibodies (αTfR1) conjugated to various classes of oligonucleotides (siRNA, ASOs and PMOs). αTfR1 AOCs delivered oligonucleotides to muscle tissue in both species. In mice, αTfR1 AOCs achieved a > 15-fold higher concentration to muscle tissue than unconjugated siRNA. A single dose of an αTfR1 conjugated to an siRNA against Ssb mRNA produced > 75% Ssb mRNA reduction in mice and monkeys, and mRNA silencing was greatest in skeletal and cardiac (striated) muscle with minimal to no activity in other major organs. In mice the EC50 for Ssb mRNA reduction in skeletal muscle was >75-fold less than in systemic tissues. Oligonucleotides conjugated to control antibodies or cholesterol produced no mRNA reduction or were 10-fold less potent, respectively. Tissue PKPD of AOCs demonstrated mRNA silencing activity primarily driven by receptor-mediated delivery in striated muscle for siRNA oligonucleotides. In mice, we show that AOC-mediated delivery is operable across various oligonucleotide modalities. AOC PKPD properties translated to higher species, providing promise for a new class of oligonucleotide therapeutics.
Real-world implementation of non-endoscopic triage testing for Barrett’s oesophagus during COVID-19
Authors: Landy R , Killcoyne S , Tang C , Juniat S , O’Donovan M , Goel N , Gehrung M , Fitzgerald R C
Published: May 2023

Background

The Coronavirus pandemic (COVID-19) curtailed endoscopy services, adding to diagnostic backlogs. Building on trial evidence for a non-endoscopic oesophageal cell collection device coupled with biomarkers (Cytosponge), an implementation pilot was launched for patients on waiting lists for reflux and Barrett’s oesophagus surveillance.

Aims

(i) To review reflux referral patterns and Barrett’s surveillance practices. (ii) To evaluate the range of Cytosponge findings and impact on endoscopy services.

Design and methods

Cytosponge data from centralized laboratory processing (trefoil factor 3 (TFF3) for intestinal metaplasia (IM), haematoxylin & eosin for cellular atypia and p53 for dysplasia) over a 2-year period were included.

Results

A total of 10 577 procedures were performed in 61 hospitals in England and Scotland, of which 92.5% (N = 9784/10 577) were sufficient for analysis. In the reflux cohort (N = 4074 with gastro-oesophageal junction sampling), 14.7% had one or more positive biomarkers (TFF3: 13.6% (N = 550/4056), p53: 0.5% (21/3974), atypia: 1.5% (N = 63/4071)), requiring endoscopy. Among samples from individuals undergoing Barrett’s surveillance (N = 5710 with sufficient gland groups), TFF3-positivity increased with segment length (odds ratio = 1.37 per cm (95% confidence interval: 1.33–1.41, P < 0.001)). Some surveillance referrals (21.5%, N = 1175/5471) had ≤1 cm segment length, of which 65.9% (707/1073) were TFF3 negative. Of all surveillance procedures, 8.3% had dysplastic biomarkers (4.0% (N = 225/5630) for p53 and 7.6% (N = 430/5694) for atypia), increasing to 11.8% (N = 420/3552) in TFF3+ cases with confirmed IM and 19.7% (N = 58/294) in ultra-long segments.

Conclusions

Cytosponge-biomarker tests enabled targeting of endoscopy services to higher-risk individuals, whereas those with TFF3 negative ultra-short segments could be reconsidered regarding their Barrett’s oesophagus status and surveillance requirements. Long-term follow-up will be important in these cohorts.
Ideology, knowledge, and the assessment of science policy agencies
Authors: Haglin Kathryn , Vedlitz Arnold
Published: May 2023

In the USA, politics often dominates the conversation surrounding science and related technologies. We also live in times of high political polarization, leading to political debate over scientific discoveries and subsequent policy implications. Given these dynamics, there is much to be learned about the politicization of science, individuals’ policy views, and the public’s relationship with the communication and interpretation of scientific findings. Agencies are often responsible for facilitating scientific research and framing its policy relevance for decision makers and the public. This paper uses data from a large national public opinion survey to investigate citizen attitudes about government science agencies. We theorize that disparities between objective and self-assessed scientific knowledge coupled with ideological cues help frame citizen evaluations of agencies. We find that individuals’ political ideologies and disparities between knowledge types shape citizen assessments of energy-related scientific agencies. These findings have important implications for our understanding of public acceptance of the work of government science agencies.
Race, Citizenship and ‘race relations’ Research in late-Twentieth-century Britain
Authors: Waters Rob
Published: May 2023

This article reads late-twentieth-century race relations research projects from the perspectives of the black and brown Britons who were the targets of research. The analysis focuses on contestations around issues of epistemic authority and resource allocation in the relationship between black citizens and the state in the post-war decades, helping us to understand why so many black citizens saw the state and its programmes of social research not as enabling or providing but surveilling and disempowering them. Relative to the dominant reading among historians of late-twentieth-century Britain of the rise of social research as a democratic story, in which ‘ordinary’ voices were listened to and given weight in the development of social policy, the study of race relations research in this article reveals a far less consensual, less democratic relationship between state-sponsored research institutions and the black and brown people who became targets of race-relations research projects. It highlights the ubiquity of challenges or evasions to those research institutions and their claims to epistemic authority, and it shows how these researches were indicted as distractions, attempts at pacification, and misuses of funds. Reading the social encounters of ‘race relations’ research as moments in which state power and state-sanctioned racial knowledge were engaged and contested reveals the steady process by which the foundations of an unpopular and ineffective ‘race relations industry’ were cast into doubt, or consent for it refused.
The ‘Bogus Child’ and the ‘Big Uncle’: The Impossible South Asian Family in Post-Imperial Britain
Authors: Natarajan Radhika
Published: May 2023

Between 1962 and 1965, a broad definition of dependence allowed for the migration of Commonwealth Citizens to join working family members in Britain. This article investigates how the Home Office targeted male dependent youth as a category that could reduce unwanted immigration from the Commonwealth, particularly South Asia. Home Office officials obscured the stories of dependent migrants, constructed the figure of the ‘bogus child’, and denigrated male familial connections, which resulted in the denial of family reunion. Colonial assumptions about the mendacity of South Asians and the illegibility of South Asian family forms shaped British policy. The 1965 White Paper and the 1968 Commonwealth Immigrants Act foreclosed the possibility of a broad definition of family and consolidated the legitimacy of the cisheterosexual family. Home Office discussions dovetailed with an emergent common sense circulated in newspapers and public debate about the illegitimacy of the South Asian family in Britain. This article interrogates the racist reasoning of the Home Office and this emergent common sense not only to show how immigration policy generates racialization but also to reveal the specificity of South Asian racialization in the post-imperial social formation.
A CRISPR-Cas9 mutation in sox9b long intergenic noncoding RNA (slincR) affects zebrafish development, behavior, and regeneration
Authors: Dasgupta Subham , LaDu Jane K , Garcia Gloria R , Li Sizhen , Tomono-Duval Konoha , Rericha Yvonne , Huang Liang , Tanguay Robyn L
Published: May 2023

The role of long noncoding RNAs (lncRNAs) regulators of toxicological responses to environmental chemicals is gaining prominence. Previously, our laboratory discovered an lncRNA, sox9b long intergenic noncoding RNA (slincR), that is activated by multiple ligands of aryl hydrocarbon receptor (AHR). Within this study, we designed a CRISPR-Cas9-mediated slincR zebrafish mutant line to better understand its biological function in presence or absence of a model AHR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The slincRosu3 line contains an 18 bp insertion within the slincR sequence that changes its predicted mRNA secondary structure. Toxicological profiling showed that slincRosu3 is equally or more sensitive to TCDD for morphological and behavioral phenotypes. Embryonic mRNA-sequencing showed differential responses of 499 or 908 genes in slincRosu3 in absence or presence of TCDD Specifically, unexposed slincRosu3 embryos showed disruptions in metabolic pathways, suggesting an endogenous role for slincR. slincRosu3 embryos also had repressed mRNA levels of sox9b—a transcription factor that slincR is known to negatively regulate. Hence, we studied cartilage development and regenerative capacity—both processes partially regulated by sox9b. Cartilage development was disrupted in slincRosu3 embryos both in presence and absence of TCDD. slincRosu3 embryos also displayed a lack of regenerative capacity of amputated tail fins, accompanied by a lack of cell proliferation. In summary, using a novel slincR mutant line, we show that a mutation in slincR can have widespread impacts on gene expression and structural development endogenously and limited, but significant impacts in presence of AHR induction that further highlights its importance in the developmental process.
Adenine nucleotide translocase: Current knowledge in post‐translational modifications, regulations and pathological implications for human diseases
Authors: Chen Yingfei , Wu Leshuang , Liu Jun , Ma Li , Zhang Wenli
Published: May 2023

Adenine nucleotide translocases (ANTs) are central to mitochondrial integrity and bioenergetic metabolism. This review aims to integrate the progresses and knowledge on ANTs over the last few years, contributing to a potential implication of ANTs for various diseases. Structures, functions, modifications, regulators and pathological implications of ANTs for human diseases are intensively demonstrated here. ANTs have four isoforms (ANT1‐4), responsible for exchanging ATP/ADP, possibly composing of pro‐apoptotic mPTP as a major component, and mediating FA‐dependent uncoupling of proton efflux. ANT can be modified by methylation, nitrosylation and nitroalkylation, acetylation, glutathionylation, phosphorylation, carbonylation and hydroxynonenal‐induced modifications. Compounds, including bongkrekic acid, atractyloside calcium, carbon monoxide, minocycline, 4‐(N‐(S‐penicillaminylacetyl)amino) phenylarsonous acid, cardiolipin, free long‐chain fatty acids, agaric acid, long chain acyl‐coenzyme A esters, all have an ability to regulate ANT activities. ANT impairment leads to bioenergetic failure and mitochondrial dysfunction, contributing to pathogenesis of diseases, such as diabetes (deficiency), heart disease (deficiency), Parkinson's disease (reduction), Sengers Syndrome (decrease), cancer (isoform shifting), Alzheimer's Disease (coaggregation with Tau), Progressive External Opthalmoplegia (mutation), and Fascioscapulohumeral muscular dystrophy (overexpression). This review improves the understanding of the mechanism of ANT in pathogenesis of human diseases, and opens a window for novel therapeutic strategies targeted on ANT in diseases.