bluuebunny/crossref_metadata_2025 huggingface dataset:
(289) SAFETY AND EFFICACY ASSESSMENT OF THE VERTICA® - A RADIO FREQUENCY DEVICE FOR THE TREATMENT OF ERECTILE DYSFUNCTION (ED)
Authors: Abou Chawareb E , Lumbiganon S , Hammad MA , Raheem OA , Reisman Y , Gruenwald I , Lischinsky D , Yafi FA
Published: December 2024

Introduction

The VERTICA® is a hand-held, home use device, designed to treat 'mild to moderate' and moderate erectile dysfunction (ED) using radiofrequency (RF) electrodes. These electrodes deliver sequential RF energy to the penile area, with additional electrodes on a pad applied to the perineal area to also cover the penile crus. We hypothesize that 1) RF energy raises penile temperature, enhancing erectile response, and 2) RF energy posits a direct structural and biochemical impact on tunical and corporal tissue, improving the tunical veno-occlusive mechanism.

Objective

The purpose of the current study is to evaluate the safety and efficacy of the VERTICA® investigational device for treatment of ED.

Methods

This study is a pivotal, prospective, randomized, controlled, double-blind clinical trial. Around 100, in our center 33 adult, heterosexual, and sexually active males (≥22 years) with mild to moderate and mild organic ED (IIEF EF score 11-21) will be enrolled and randomized 1:1 for Active or Sham VERTICA® treatment. Patients are instructed to use the device 3 times a week for 4 weeks (12 treatments), twice a week for an additional 4 weeks (8 treatments) and then 1-2 times a week for another 4 months. Every treatment comprises a 15-minute session involving ring electrodes, followed by an additional 15-minute session incorporating both ring and pad electrodes. Compliance and treatment data is monitored using a smartphone app. Subjects are instructed to attempt sexual activity weekly or 6 times a month, logging events in the Sexual Encounter Profile (SEP) form. Monthly follow-up assessments at months 1, 2, 3, and 6 include evaluating the efficacy of the treatment using the IIEF-EF, SEP, EHS, EDITS, and SHIM questionnaires. Enhancements in ED will be measured by comparing the scores of these questionnaires within both groups and, for every individual, before and after completing the study.

Results

A pilot study with 28 subjects demonstrated the device's safety and efficacy, with no serious adverse events reported in 144 treatment sessions.

Conclusions

In conclusion, the VERTICA® investigational device shows promise in the treatment of mild to moderate erectile dysfunction (ED) based on the pilot study and the ongoing pivotal clinical trial. If the results of this trial are promising, the VERTICA® device could offer a novel and effective treatment option for men with mild to moderate ED, potentially improving their quality of life and sexual health.

Disclosure

Yes, this is sponsored by industry/sponsor: Ohhmed.

Clarification: Industry funding only - investigator initiated and executed study.

Any of the authors act as a consultant, employee or shareholder of an industry for: Sprout.
(295) EARLY PLACEMENT OF INFLATABLE PENILE PROSTHESIS FOLLOWING PENOSCROTAL DECOMPRESSION
Authors: Tabei SS , Raheem O
Published: December 2024

Introduction

Ischemic priapism is the most common form of priapism which accounts for up to 95% of the cases. Prolonged ischemic priapism is associated with a higher risk of corpus spongiosum fibrosis and the development of erectile dysfunction. Studies have shown that treatment of ischemic priapism under 12 hours has an excellent prognosis and may prevent erectile dysfunction in 100% of cases. On the other end of the spectrum, ischemic priapism >36 hours may lead to permanent loss of erectile function in virtually all cases.

Objective

One of the newer procedures applied in cases of refractory priapism is the penoscrotal decompression approach which is technically similar to the inflatable penile prosthesis insertion technique. In cases of failed distal shunting, this procedure has proven to be useful in small-scale studies. In this method, a penoscrotal incision is made followed by corporotomy and and corporal dilation. It is suggested that penoscrotal decompression may be favorable to early IPP placement from an economical standpoint.

Methods

In our experience, a 42-year-old individual presented with a prolonged episode of ischemic priapism for approximately 36 hours which did not achieve detumescence by conservative management. A shared decision was made to proceed with penoscrotal decompression. However, the patient was unable to achieve detumescence after the procedure. We decided to insert a three-piece IPP approximately 48 hours after the penoscrotal decompression procedure. A separate inguinal counter-incision was made for reservoir placement according to the established protocols for IPP placement.

Results

Penoscrotal decompression may not always provide favorable outcomes and maintaining erectile function by IPP implantation may be considered afterwards.

Conclusions

The insertion of the prosthesis following penoscrotal decompression is more challenging than the normal setting as the primary priapism leads to more blood clot formation and intracavernosal adhesion and fibrosis.

Disclosure

No.
(296) SALVAGE VAGINOPLASTY WITH SINGLE-PORT ROBOT ASSISTED TUBULARIZED URACHUS PERITONEAL HINGE FLAP: TECHNIQUE HIGHLIGHTS, OUTCOMES, AND AN EVIDENCE-BASED PROPOSAL FOR HOW AND WHEN TO USE (AND NOT USE!) PERITONEUM WITH VAGINOPLASTY
Authors: Shiang A , Sandhu S , Smith S , Mallavarapu S , Stelmar J , Yuan N , Gupta A , Kim H , Garcia M
Published: December 2024

Introduction

Currently, only two published gender-affirming vaginoplasty techniques describe using peritoneal tissue to contribute to the neovaginal canal: The modified Davydov technique, first described by Zhao et al (2019), and the Tubularized Urachus-Peritoneal Hinge Flap, described by Garcia et al (2022). Today, many providers use the Davydov technique at the time of primary vaginoplasty, while other providers argue that use of peritoneum is not necessary at the time of primary vaginoplasty. We use peritoneum (urachus-flap) only for salvage surgery.

Objective

We report urachus hinge-flap technical innovations, and clinical outcomes at 1.5-years postoperatively. We also review the literature to determine whether there is evidence to support using peritoneum at time of primary vaginoplasty.

Methods

We review our single-port robot-assisted urachus hinge flap technique to augment neovaginal depth following primary vaginoplasty. We also review technical innovations to maximize neovaginal depth with primary vaginoplasty using only penile and scrotal skin. We present our literature review, and posit a theory that explains why, regardless of PV technique, mean neovaginal depth is 11-13 cm in all series.

Results

Our mean neovaginal depth after salvage urachus hinge flap technique is 12.5 cm (range 11-14.2) at 409 days post-op, comparable to the Davydov technique. With primary vaginoplasty using only penile and scrotal skin, our mean depth is 12.5 cm, which is comparable to other series (Fig. 1). We use video to show how, with the Davydov technique, rectum and bowel are pulled deep into the pelvis post-op, which increases risk of bowel injury at time of salvage surgery with intestine (URL: https://youtu.be/z3pQrNY-A5I).

Conclusions

By the techniques described herein, we are able to achieve comparable vaginal depth as other groups that use the “pull-through” technique. We suggest that peritoneum is only rarely necessary at primary vaginoplasty, and should be reserved for use as a salvage surgery if needed. The urachus flap is a safer alternative to the Davydov technique if and when PV fails and salvage intestinal vaginoplasty must be undertaken.

Disclosure

No.
(299) EJACULATORY INSIGHT OF A SOUTH FLORIDA COHORT USING A MODIFIED EJACULATION SCORE QUESTIONNAIRE
Authors: Farias A , Cruz J , Defauwes N , Prabhakar P , Martinez D , Caso J
Published: December 2024

Introduction

Elements like erection and orgasm have been the main focus regarding male sexual health, overshadowing ejaculation in the comprehension and study of male sexual function.

Objective

We modified an ejaculation score questionnaire to assess the ejaculatory process and identify ejaculatory dysfunction. In addition to the questions to score and evaluate ejaculatory dysfunction, we included questions to apprehend the patient’s perspective of an ideal ejaculation.

Methods

At a male sexual health outpatient clinic in South Florida, patients were given an 11-question self-administered ejaculation score. These patients were not seeking care for ejaculatory disorders. Elements such as force, consistency, volume, and the significance of these factors were incorporated into the questionnaire to understand the patient’s perception of an ideal ejaculation. In addition, we explored whether having difficulties with ejaculation was bothersome and the importance of ejaculation for sexual satisfaction. All the responses were recorded and analyzed for further evaluation.

Results

Of the 221 patients who finished the self-administered questionnaire, those who particularly responded to the questions about their perception of ejaculation were evaluated. A substantial majority, 70% (126/180), preferred “Strong (Shoots out)” as their ideal force of ejaculation. A considerable 62.2% (107/172) favored a “Moderate (½ a shot glass)” amount regarding the ideal volume of semen expelled. Similarly, 54.4% (93/171) considered “Thin/thick, chunky” as an ideal consistency. Furthermore, 47.9% (79/165) of participants experiencing difficulties with ejaculation answered “A lot” when asked if it was a bother. Finally, a significant 81.2% (138/170) of respondents expressed the notable importance of ejaculation to the male sexual orgasm.

Conclusions

This ongoing pilot investigation gained valuable insights into the perceptions of ejaculation. This study can be a foundation for healthcare providers to improve patient-centered care by recognizing and addressing individual preferences and concerns. Thus, it provides enhanced support for patients so they can attain healthy and gratifying sexual experiences, thus improving their quality of life.

Disclosure

No.
(300) SEXUAL HEALTH PRACTITIONER PATTERNS FOR THE ASSESSMENT OF PATIENTS’ ORGASM CONCERNS
Authors: Burr E , Messafi A , Agrawal J , Perlmuter S , Forer R , Tran Q , Poirier E , Rubin R
Published: December 2024

Introduction

Medical knowledge of orgasm dysfunction has shifted in recent years to include a wide range of conditions that impact multiple domains of orgasm. It is currently unknown how sexual medicine practitioners are adjusting their practice patterns to ensure comprehensive assessment of patients’ orgasm concerns.

Objective

This study aims to elucidate the current state of orgasm assessment by surveying sexual medicine practitioners. This study’s primary outcome was to identify the method of orgasm assessment utilized by sexual medicine practitioners, exploring both the use of patient reported outcome measures (PROMs) and patient interviews. A secondary outcome was to explore practitioner reasons for utilizing their assessment tool as well as satisfaction with their current practice pattern.

Methods

Data were collected via an anonymous 33-question survey distributed from January 7, 2024, to April 14, 2024. The survey asked participants about their practice patterns for assessing orgasm via multiple choice and free response. Qualtrics software was used to create, distribute, and analyze the survey and NVivo14 was used to perform qualitative analysis.

Results

Of the 87 survey responses analyzed, 86 (99%) practitioners felt that it is important to assess orgasm as part of sexual health. Most respondents utilized interviews, with 56% of respondents using patient interviews alone and 34% combining interviews with validated PROMs. Regardless of the assessment modality, approximately 25% of the respondents expressed dissatisfaction with the current modalities for assessing orgasm function. Qualitative responses emphasized the benefits of interviews, including their ability to support detailed and individualized care. Additional barriers to using PROMs included practice limitations such as lack of time and practitioner lack of knowledge about and confidence in orgasm-specific PROMs.

Conclusions

This study’s findings suggest a significant reliance on interviews over standardized PROMs for assessing orgasm, likely due to the complex, multifactorial nature of orgasm dysfunction as well as lack of knowledge about or confidence in existing orgasm-specific PROMs. Respondents’ dissatisfaction with existing assessment modalities indicates a potential gap in adequate tools to address orgasm dysfunction. Future research should focus on developing more comprehensive, patient-centered assessment strategies that retain qualities of interviews and PROMs.

Disclosure

No.
(317) EVALUATING PRACTICE PATTERNS OF CLOSTRIDIUM COLLAGENASE HISTOLYTICUM PROVIDERS
Authors: Vasdev R , Parikh N , Sischka M , Ziegelmann M
Published: December 2024

Introduction

Clostridium Collagenase Histolyticum (CCH) is the only-FDA approved non-surgical, intralesional option for men with Peyronie’s disease. However, little is known regarding practice patterns of CCH providers due to lack of standardized protocols.

Objective

To evaluate practice patterns for providers approved to administer CCH to treat Peyronie’s disease (PD), this study was conducted.

Methods

The “Find a Xiaflex-Trained Urologist” search tool on the Endo International patient-facing website was utilized to identify clinicians offering CCH injections in the United States. A 24-question survey was mailed to these providers with topics including provider type, years in practice, therapies offered, and patient evaluation was distributed to providers on patient-facing Endo International Xiaflex Find a Provider web-based tool.

Results

63 responses were obtained, including 41% fellowship-trained urologists (FTU), 40% non-fellowship-trained urologists (NFTU), 14% advanced practice providers, and 5% un-specified. Prior to therapy, over 63% of providers performed in-office assessment of an erect penis while only 35% obtained ultrasound. 32% always and 36% never performed an artificial erection prior to administering CCH. Plaques were most identified by palpation or patient-provided direction with penile modeling and traction the most common adjuncts. When comparing NFTU to FTU, there was no difference in volume of PD patients with 60% examining fewer than 10 per month. FTU were more likely to offer traction (p = 0.002), plaque incision/excision and grafting (p = 0.005), increase time between injections (p = 0.012), and less likely to encourage penetrative intercourse between cycles (p = 0.016). The incidence of post-operative hematomas or suspected corporal rupture was not significantly different, although FTUs were more likely to conservatively manage rupture.

Conclusions

Variability exists in provider practice patterns surrounding CCH injections with most evaluating less than 10 patients with PD per month. This calls to attention the need for evaluation of techniques, patient outcomes, and standardization of care.

Disclosure

Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals.

Clarification: Industry funding only - investigator initiated and executed study.

Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Pharmaceuticals.
(322) PATIENT OUT-OF-POCKET COSTS FOR GUIDELINE-RECOMMENDED TREATMENTS FOR ERECTILE DYSFUNCTION: A MEDICARE COST MODELING ANALYSIS
Authors: Nguyen V , Mcgovern A , Rojanasarot S , Patel D , Bhattacharyya S , Hargens L , Aworunse O , Hsieh T
Published: December 2024

Introduction

Patient out-of-pocket (OOP) cost represents a barrier to accessing treatment for erectile dysfunction (ED). Many physicians have limited insight into the costs and insurance coverage of the treatment options that they recommend.

Objective

We sought to evaluate OOP costs incurred by men with ED covered by Fee-for-Service Medicare.

Methods

The 2018 American Urological Association (AUA) guidelines were used to identify recommended ED treatments. Coverage policies were obtained from the Medicare Coverage Database. OOP costs were retrieved from the 2023 CMS Final Rule. For treatments not covered by Medicare, OOP costs were extracted from GoodRx® or published literature and inflated to 2022 dollars. Annual prescription costs were calculated using a published estimate of 52.2 instances of sexual intercourse per year. The estimated number of Medicare patients with ED (n = 254,650) was used to evaluate healthcare system implications.

Results

Medicare has established coverage for inflatable penile prostheses (IPP; strong recommendation), non-coverage for vacuum erection devices (VED; moderate recommendation) and phosphodiesterase type-5 inhibitors (PDE5i; strong recommendation), and no existing policies for intracavernosal injections (ICI; moderate recommendation), intraurethral alprostadil (IA; conditional recommendation), or extracorporeal shock wave therapy (ESWT; conditional/investigational recommendation; Table 1). Annual IA prescription is associated with the highest patient OOP cost ($4,022), followed by annual ICI prescription ($3,947), one ESWT treatment course ($3,445), IPP ($1,600; inpatient deductible), annual PDE5i prescription ($696), and one VED ($213; Fig. 1). Among PDE5i, avanafil is associated with the highest annual OOP cost ($3,455), followed by vardenafil ($2,102), tadalafil ($723), and sildenafil ($459). One-year projections demonstrate IA is associated with the highest national healthcare OOP cost ($1.02 billion), followed by ICI ($1.0 billion), ESWT ($877 million), IPP ($407 million), PDE5i ($177 million), and VED ($54 million).

Conclusions

PDE5i and IPP are cost-effective options with strong guideline recommendations. Better understanding of patient financial burden may improve shared decision making with patients who suffer from ED.

Disclosure

Yes, this is sponsored by industry/sponsor: Boston Scientific.

Clarification: Industry funding only - investigator initiated and executed study.

Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific.
(324) EX-VIVO DEMONSTRATION OF A NOVEL METHOD FOR AUTO-INFLATION PREVENTION IN PATIENTS WITH INFLATABLE PENILE PROSTHESIS
Authors: Howell S , Mahdi M , Albakr A , Wang R
Published: December 2024

Introduction

Inflatable penile prosthesis (IPP) is a surgical treatment for refractory erectile dysfunction which has repeatedly demonstrated a high patient and partner satisfaction rate. Three-piece IPPs are associated with the highest satisfaction of different implants due to alternating excellent rigidity and flaccidity. Despite the high satisfaction rate enabled by the reservoir, mechanical dysfunction associated with this piece may conversely lead to poor satisfaction and re-intervention. One reported mechanical dysfunction is auto-inflation, in which there is propagation of fluid from the reservoir to the cylinders without manual action on the pump. Auto-inflation leads to annoyance and discomfort at best. At worst, significant morbidity has been reported including device erosion into the urethra. To overcome auto-inflation, Coloplast devices contain a lockout valve in the reservoir itself, while Boston Scientific devices have the lockout valve in the pump. Nevertheless, auto-inflation remains a source of dissatisfaction, with management potentially requiring revisional surgery in patients with significant bother.

Objective

We describe a simple technique for prevention of auto-inflation of inflatable penile prostheses (IPP) by using 1-2 pump squeezes and demonstrate this ex-vivo.

Methods

The pump/cylinder units of both Coloplast Titan and Boston Scientific AMS 700 devices were tested separately within the operating room. Auto-inflation Simulation: A 60 cc Luer lock syringe is used to inject normal saline solution into the pump/cylinders while the device is in deflation mode. A reasonable pressure is applied during injection. Cylinder inflation is observed only in the Titan device, suggesting potential auto-inflation. Prevention Maneuver: The Titan cylinders are manually deflated. Following this, the pump is squeezed once or twice. The Luer lock syringe is then used to attempt to inject normal saline, but in this case is unsuccessful using reasonable pressure application. Confirmatory Maneuver: The above procedure is repeated for the AMS 700 device. Normal saline is still unable to be propagated into the cylinder after 1-2 squeezes of the pump.

Results

Our findings demonstrate that the simple maneuver of one to two pump squeezes after deflation effectively prevents auto-inflation in the Coloplast Titan IPP. The efficacy of this technique has been further validated in a clinical setting. Five patients experiencing auto-inflation with the Titan device were treated using this maneuver, and it successfully resolved the issue in all cases.

Conclusions

The simple technique of one to two pump squeezes after IPP device deflation demonstrates a non-invasive method for prevention of IPP auto-inflation.

Disclosure

No.
Primaquine treatment for P. ovale infection in migrants with G6PD deficiency
Authors: Rubio Maturana Carles , Martínez-Vallejo Patricia , Salvador Fernando , Beneitez-Pastor David , Serrat Francesc Zarzuela , Sulleiro Elena , Pou Diana , Aznar Maria Luisa , Molina Israel , Serre-Delcor Núria , Oliveira-Souto Inés
Published: December 2024

Four patients from Sub-Saharan Africa were infected by Plasmodium ovale and simultaneously presented with glucose-6-phosphate dehydrogenase deficiency. Primaquine 0.75 mg/kg once a week during 8 weeks was administered with a close hematologic follow-up. Non-significant alterations in hemogram and hemolytic parameters were observed in any case.
Chinese Whispers: Contextualizing the Finale of Messiaen’s Et exspecto
Authors: Cheong Wai-Ling , Tse Chun-Yan
Published: December 2024

The incessant, evenly spaced tolling of gongs throughout the 6-minute-long finale of Olivier Messiaen’s Et exspecto resurrectionem mortuorum presents a unique sonic phenomenon within the Western orchestral tradition. It nonetheless resonates with distinct features of the ‘Hymne du temple des Ancêtres’ and the ‘Hymne à Confucius’ Messiaen cited under the section ‘Les modes Chinois’ in Traité de rythme, de couleur, et d’ornithologie, volume vii. Through a comparative analysis of Western and Chinese sources related to the two hymns, we garner evidence to argue for cross-cultural intertextuality in Messiaen’s finale, and to speculate on the sources he might have (mis)read when commenting intriguingly on the Chinese modes and religious music prior to citing the specific hymns. Not least because the two hymns are emblematic of the Ming and the Qing dynasty, the story of their transmission to the West—arguably politically motivated—also throws light on the power dynamics between the rival dynasties.
The formation of supermassive black holes from Population III.1 seeds. III. Galaxy evolution and black hole growth from semi-analytic modelling
Authors: Cammelli Vieri , Monaco Pierluigi , Tan Jonathan C , Singh Jasbir , Fontanot Fabio , De Lucia Gabriella , Hirschmann Michaela , Xie Lizhi
Published: December 2024

We present an implementation of Pop III.1 seeding of supermassive black holes (SMBHs) in a theoretical model of galaxy formation and evolution to assess the growth of the SMBH population and the properties of the host galaxies. The model of Pop III.1 seeding involves SMBH formation at redshifts $z\gtrsim 20$ in dark matter minihaloes that are isolated from external radiative feedback, parametrized by isolation distance $d_{\rm iso}$. Within a standard $\Lambda$CDM cosmology, we generate dark matter haloes using the code pinocchio and seed them according to the Pop III.1 scenario, exploring values of $d_{\rm iso}$ from 50 to 100 kpc (proper distance). We consider two alternative cases of SMBH seeding: a halo mass threshold model in which all haloes $\gt 7\times 10^{10}\,\rm M_\odot$ are seeded with $\sim 10^5\,\rm M_\odot$ black holes; an all light seed model in which all haloes are seeded with low, stellar mass black holes. We follow the redshift evolution of the haloes, populating them with galaxies using the GAlaxy Evolution and Assembly theoretical model of galaxy formation, including accretion on SMBHs and related feedback processes. Here we present predictions for the properties of galaxy populations, focusing on stellar masses, star formation rates, and black hole masses. The local, $z\sim 0$ metrics of occupation fraction as a function of the galaxy stellar mass, galaxy stellar mass function, and black hole mass function all suggest a constraint of $d_{\rm iso}\lt 75\:$ kpc. We discuss the implications of this result for the Pop III.1 seeding mechanism.
Rotation signal on the full disc of the solar chromosphere
Authors: Wan M , Deng L H , Zeng S G , Yan Z J , Xie J L , Xu T T , Yu Y T
Published: December 2024

The rotation signal on the full disc of the solar chromosphere was studied by using the Ca ii K normalized intensity from 938 Carrington rotation (CR) synoptic maps (from CR827 to CR1764) obtained from the Mount Wilson Observatory during the period of 1915 August 10 to 1985 July 7. In this study, our main focus is on the distribution characteristics of the rotation signal on the full disc of the solar chromosphere and its variation with the solar cycle. We found that the chromospheric rotation signal is more pronounced in the latitudinal belt of sunspot activity and tends to extend to higher latitudes, and the trend is essentially the same for each solar cycle. The chromospheric rotation signal is also found to have phase differences in latitudes. The period of the chromospheric rotation signal varies regularly in latitudes, but its phase variation is irregular. In addition, we found that the intensity background is lowest in the latitudinal belt of sunspot drift where the chromospheric rotation signal is generated, but it increases with latitude and tends to extend to higher latitudes. We discussed the possible mechanisms of the above analysis results and thought that the chromospheric rotation signal is mainly caused by sunspots and plages.
HD 60435: the star that stopped pulsating
Authors: Kurtz Donald W , Handler Gerald , Holdsworth Daniel L , Cunha Margarida S , Saio Hideyuki , Medupe Thebe , Murphy Simon J , Krüger Joachim , Brunsden E , Antoci Victoria , Hey Daniel R , Shitrit Noi , Matthews Jaymie M
Published: December 2024

HD 60435 is a well known rapidly oscillating (roAp) Ap star with a series of alternating even and odd degree modes, making it a prime asteroseismic target. It is also an oblique pulsator with rotational inclination, i, and magnetic/pulsation obliquity, $\beta$, such that both magnetic/pulsation poles are viewed over the rotation period, $P_{\rm rot} = 7.679696$ d, determined from rotational light variations. While some roAp stars have stable pulsation mode amplitudes over decades, HD 60435 is known to have amplitude variations on time-scales as short as 1 d. We show from 5 yr of TESS observations that there is strong amplitude modulation on this short time-scale with possible mode interactions. Most remarkably, HD 60435 stopped pulsating during the time span of the TESS observations. This is the first time that any pulsating star has been observed to cease pulsating entirely. That has implications for mode interaction, excitation and damping, and is relevant to the problem of why only some stars in many pulsation instability strips pulsate, while others do not. During a 24.45-d time span of the TESS data when there was mode stability for a dipole mode and a quadrupole mode, the oblique pulsator model constrained i and $\beta$, which we used to model those modes with a magnetic pulsation model from which we determined a polar field strength of 4 kG, in good agreement with a known magnetic measurement. We modelled the frequency separations showing that they can constrain the global metallicity, something that is not possible from spectroscopy of the highly peculiar Ap atmosphere.
Laboratory markers predicting tofacitinib efficacy in Japanese patients with rheumatoid arthritis: A pooled analysis of Phase 2/3 randomised controlled clinical trials
Authors: Tanaka Yoshiya , Yamanaka Hisashi , Toyoizumi Shigeyuki , Hirose Tomohiro , Takeuchi Tsutomu
Published: December 2024

Objectives

We characterised early changes in laboratory parameters in Japanese patients with rheumatoid arthritis and assessed whether these changes at Month (M)1 were predictive of tofacitinib efficacy at M3.

Methods

This post hoc analysis included pooled data from Japanese patients receiving tofacitinib or placebo in three Phase 2/Phase 3 studies (NCT00603512; NCT00687193; NCT00847613). Outcomes included changes from baseline in laboratory parameters (Week 2 and M1/3); efficacy end points were Disease Activity Score in 28 joints, based on C-reactive protein; Disease Activity Score in 28 joints, based on erythrocyte sedimentation rate; and American College of Rheumatology-N index at M3. Univariate/multivariable analyses assessed whether changes at M1 were predictive of efficacy at M3.

Results

Overall, 467 patients receiving tofacitinib and 104 receiving placebo were included. Tofacitinib treatment was associated with decreases from baseline in C-reactive protein, erythrocyte sedimentation rate, neutrophils, and platelets and increases in lymphocytes, haemoglobin, and lipids up to M3. Decreased platelet count and increased low-density lipoprotein cholesterol and haemoglobin at M1 were predictive of changes in efficacy outcomes at M3.

Conclusions

Changes in laboratory parameters at M1 could potentially be used to assess whether tofacitinib therapy will be effective at M3; however, further investigation is needed.
FTLD-MAPT mutations and short 5′UTR Tau mRNAs increase Tau translation
Authors: da Costa Paulo J , Perret Antoine , Buée Luc , Hamdane Malika , Martin Franck
Published: December 2024

Tau protein plays a central role in Alzheimer’s disease (AD) and other tauopathies. Tau proteins aggregate in degenerating neurons and their expression level is critical for disease development and progression. In addition, the generation of truncated Tau species is involved in the pathological process. In the human brain, several N-terminally truncated Tau species (including Met11- and Met127-Tau) have been detected. However, both the mechanisms of their synthesis and their relevance for the diseases remain largely unclear. Several Tau messenger RNA (mRNA) isoforms with distinct 5′ untranslated regions (5′UTRs) were found in brains with tauopathies. In addition, single substitutions in the N-terminal coding sequence of Tau, namely R5H, R5L and R5C, have been associated with AD, progressive supranuclear palsy and Parkinson’s disease, respectively. Here, we investigated how the 5′ end of Tau mRNAs and the N-terminal mutations affect Tau protein synthesis. We show that both the length of the 5′UTR of Tau mRNAs and the N-terminal coding sequence largely modulate the expression level of Tau. Truncated Tau protein species are generated by an alternative translation initiation event. Thereafter, we show that the disease-associated mutations at codon #5 also increase the expression, mostly due to secondary structure modifications of the corresponding mRNAs.
The novel DNA cross-linking agent KL-50 is active against patient-derived models of new and recurrent post-temozolomide mismatch repair-deficient glioblastoma
Authors: McCord Matthew , Sears Thomas , Wang Wenxia , Chaliparambil Rahul , An Shejuan , Sarkaria Jann , James C David , Ruggeri Bruce , Gueble Susan , Bindra Ranjit , Horbinski Craig
Published: December 2024

Background

Acquired resistance to temozolomide (TMZ) chemotherapy due to DNA mismatch repair (MMR) enzyme deficiency is a barrier to improving outcomes for IDH wild-type glioblastoma (GBM) patients. KL-50 is a new imidazotetrazine-based therapeutic designed to induce DNA interstrand cross links, and subsequent double-stranded breaks, in an MMR-independent manner in cells with O-6-Methylguanine-DNA Methyltransferase (MGMT) deficiency. Previous research showed its efficacy against LN229 glioma cells with MMR and MGMT knockdown. Its activity against patient-derived GBM that model post-TMZ recurrent tumors is unclear.

Methods

We created MMR-deficient GBM patient-derived xenografts through exposure to TMZ, followed by treatment with additional TMZ or KL-50. We also generated isogenic, MSH6 knockout patient-derived GBM and tested them for sensitivity to TMZ and KL-50.

Results

KL-50 extended the median survival of mice intracranially engrafted with either patient-derived TMZ-naïve GBM6 or TMZ-naïve GBM12 by 1.75-fold and 2.15-fold, respectively (p<0.0001). A low dose (4 Gy) of fractionated RT further extended the survival of KL-50 treated GBM12 mice (median survival=80 days for RT+ KL-50 vs. 71 days KL-50 alone, P=0.018). KL-50 also extended the median survival of mice engrafted with post-TMZ, MMR-deficient GBM6R-m185 (140 days for KL-50 vs. 37 days for vehicle, p<0.0001). MSH6-KO increased TMZ IC50 for GBM6 and GBM12 cultures by >5-fold and >12-fold for cell death and live cell count outputs, respectively. In contrast, MSH6-KO actually decreased KL-50 IC50 by 10-80%.

Conclusion

KL-50-based compounds are a promising new strategy for the treatment of MGMT-deficient, MMR-deficient GBM that recurs after frontline TMZ.
A bio-inspired microwave wireless system for constituting passive and maintenance-free IoT networks
Authors: Yu Buyun , Wang Hong-Qin , Ju Lu , Hou Ke-Xin , Xiao Zhi-Da , Zhan Jun-Lin , Zhang Chao , Chen Hao , Wang Binghao , Liu Zhen-Guo , Guan Ying-Shi , Li Cheng-Hui , Cui Tie Jun , Lu Wei-Bing
Published: December 2024

With the rapid expansion of wireless networks, the deployment and long-term maintenance of distributed microwave terminals have become increasingly challenging. To address these issues, we present a bio-inspired microwave system to constitute passive and maintenance-free wireless networks. Drawing inspiration from vertebrate skeletons and skins, we employ stimuli-responsive polymer with tunable stiffness to support and protect sensitive electromagnetic structures, and synthesize self-healable skin-like polymer for system encapsulation. Owing to the biomimetic strategy, our system combines outstanding flexibility, electromagnetic stability, structural robustness, and self-healable performance. On the other hand, to address power supply issues, our system modulates ambient electromagnetic waves to achieve long-range wireless communication, and the hybrid energy harvesting strategy allows the system to capture energy from ambient light and microwaves, thereby eliminating the need for batteries or power cables. Multidisciplinary innovation enables our system to be deployed almost anywhere and supports stable, battery-less, and maintenance-free wireless communication.
Plague Correspondence, Rumour, and Mistrust in the Late Medieval Crown of Aragon
Authors: Agresta Abigail
Published: December 2024

Starting in the fifteenth century, European city governments began to respond to the threat of plague by introducing quarantine measures, which presumed that risk arrived in the bodies and goods of travellers. The adoption of quarantine was long considered a milestone on the road to modern, rational public health and was linked to increased centralization and the rise of state power in the early modern period. Recent quarantine scholarship, however, is revealing a more contingent story. This paper uses surviving plague correspondence between the governments of Barcelona, Valencia, and Ciutat de Mallorca (now Palma) to uncover the chaotic practice of early quarantine in the late medieval Crown of Aragon. All three cities adopted quarantine in the later fifteenth century, but all of them also obscured their own health statuses and distrusted one another’s information about plague. Municipalities in the Crown of Aragon embraced quarantine during this period even as their correspondence thwarted cooperative plague control. The exigencies of quarantine demanded plague information in the form of fama (rumour or reputation), often linked to the behaviour of elites.
Public attitudes on performance for algorithmic and human decision-makers
Authors: Bansak Kirk , Paulson Elisabeth
Published: December 2024

This study explores public preferences for algorithmic and human decision-makers (DMs) in high-stakes contexts, how these preferences are shaped by performance metrics, and whether public evaluations of performance differ depending on the type of DM. Leveraging a conjoint experimental design, approximately 9,000 respondents chose between pairs of DM profiles in two high-stakes scenarios: pretrial release decisions and bank loan approvals. The profiles varied by type (human vs. algorithm) and three metrics—defendant crime rate/loan default rate, false positive rate (FPR) among white defendants/applicants, and FPR among minority defendants/applicants—as well as an implicit fairness metric defined by the absolute difference between the two FPRs. The results show that efficiency was the most important performance metric in the respondents’ evaluation of DMs, while fairness was the least prioritized. This finding is robust across both scenarios, key subgroups of respondents (e.g. by race and political party), and across the DM type under evaluation. Additionally, even when controlling for performance, we find an average preference for human DMs over algorithmic ones, though this preference varied significantly across respondents. Overall, these findings show that while respondents differ in their preferences over DM type, they are generally consistent in the performance metrics they desire.
Antibody-mediated clearance of an ER-resident aggregate that causes glaucoma
Authors: Ma Minh Thu , Qerqez Ahlam N , Hill Kamisha R , Azouz Laura R , Youngblood Hannah A , Hill Shannon E , Ku Yemo , Peters Donna M , Maynard Jennifer A , Lieberman Raquel L
Published: December 2024

Recombinant antibodies are a promising class of therapeutics to treat protein misfolding associated with neurodegenerative diseases, and several antibodies that inhibit aggregation are approved or in clinical trials to treat Alzheimer's disease. Here, we developed antibodies targeting the aggregation-prone β-propeller olfactomedin (OLF) domain of myocilin, variants of which comprise the strongest genetic link to glaucoma and cause early onset vision loss for several million individuals worldwide. Mutant myocilin aggregates intracellularly in the endoplasmic reticulum (ER). Subsequent ER stress causes cytotoxicity that hastens dysregulation of intraocular pressure, the primary risk factor for most forms of glaucoma. Our antibody discovery campaign yielded two recombinant antibodies: anti-OLF1 recognizes a linear epitope, while anti-OLF2 is selective for natively folded OLF and inhibits aggregation in vitro. By binding OLF, these antibodies engage autophagy/lysosomal degradation to promote degradation of two pathogenic mutant myocilins. This work demonstrates the potential for therapeutic antibodies to disrupt ER-localized protein aggregates by altering the fate of folding intermediates. This approach could be translated as a precision medicine to treat myocilin-associated glaucoma with in situ antibody expression. More generally, the study supports the approach of enhancing lysosomal degradation to treat proteostasis decline in glaucoma and other diseases.
Does household income predict health and educational outcomes in childhood better than neighbourhood deprivation?
Authors: Skarda Ieva , Cookson Richard , Gilbert Ruth
Published: December 2024

Background

Public health research and prevention policies often use the small area Index of Multiple Deprivation (IMD) at neighbourhood level to proxy individual socio-economic status because it is readily available. We investigated what household income adds to IMD in early childhood for predicting adverse health in adolescence.

Methods

Using data from the Millennium Cohort Study, we analysed IMD and self-reported equivalised household income (ages 0–5) to predict outcomes at age 17: poor academic achievement, psychological distress, poor health, smoking, and obesity. Predictions were compared using IMD quintile groups alone, household income quintile groups alone, and both together.

Results

Household income was a stronger and more consistent predictor of age 17 outcomes than IMD and revealed inequalities within neighbourhoods. Decreasing household income showed steep gradients in educational attainment and smoking across all IMD quintiles, and moderate gradients in obesity, psychological distress and poor health in most quintiles. IMD did not predict smoking or psychological distress within any income group, or educational attainment within the poorest income group.

Conclusions

Household income is associated with inequality gradients within all quintiles of neighbourhood IMD. Early childhood public health strategies should consider household income in combination with neighbourhood deprivation.
Performance characteristics of the point-of-care tests for HPV-based cervical cancer screening: a systematic review and meta-analysis
Authors: Gupta Ruchika , Singh Sompal , Gupta Sanjay
Published: December 2024

Background

We aimed to conduct an updated and comprehensive summary of the sensitivity and specificity of three human papillomavirus (HPV) point-of-care (POC) tests (careHPV™, oncoE6™ cervical test, Xpert® HPV) to guide resource-constrained countries for their implementation in cervical cancer screening.

Methods

Databases including Medline, Embase, Web of Science and cumulated index in nursing and allied health literature (CINAHL) were searched between January 2004 and October 2024. Observational studies analyzing the three tests for cervical cancer screening were included. Pooled estimates for the performance characteristics were calculated using random-effect models.

Findings

Of the 3976 records, 33 studies were included. The sensitivity and specificity of careHPV™ for detection of CIN2+ lesions in self-collected samples were 75.6% and 85.6% compared to 86.4% and 80.4% for physician-collected samples. The sensitivity and specificity of OncoE6™ cervical test were 54.5% and 98.4%, respectively, for physician-collected samples. Xpert® HPV had a sensitivity and specificity of 91.5% and 56.5% in self-collected vaginal samples (SCSs), 92.3% and 53.3%, respectively, in physician-collected cervical samples.

Interpretation

Both careHPV™ and Xpert® HPV have a good sensitivity and specificity as a POC cervical cancer screening method. These methods also hold potential for use on SCSs.

Funding

None.
Dynamic problem of a power-law graded half-plane and an associated carleman problem for two functions
Authors: Antipov Y A
Published: December 2024

A steady state plane problem of an inhomogeneous half-plane subjected to a load running along the boundary at subsonic speed is analyzed. The Lame coefficients and the density of the half-plane are assumed to be power functions of depth. The model is different from the standard static model have been used in contact mechanics since the Sixties and originated from the 1964 Rostovtsev exact solution of the Flamant problem of a power-law graded half-plane. To solve the governing dynamic equations with variable coefficients written in terms of the displacements, we propose a method that, by means of the Fourier and Mellin transforms, maps the model problem into a Carleman boundary value problem for two meromorphic functions in a strip with two shifts or, equivalently, to a system of two difference equations of the second order with variable coefficients. By partial factorization the Carleman problem is recast as a system of four singular integral equations on a segment with a fixed singularity and highly oscillating coefficients. A numerical method for its solution is proposed and tested. Numerical results for the displacement and stress fields are presented and discussed.
Compact SNMR sensors: a sensitivity study
Authors: Splith T , Müller-Petke M
Published: December 2024

Extending surface nuclear magnetic resonance (SNMR) with pre-polarization (PP) enables mobile compact SNMR layouts, that are promising for soil moisture investigations. The pre-polarization introduces additional parameters into the SNMR experiment, and therefore predicting the resolution performance of a specific PP SNMR layout becomes more complicated. In this paper, we use the numerical integral over the diagonal elements of the resolution matrix in the target depth range to evaluate the resolution performance of a large number of possible PP SNMR layouts. We also apply this approach to the recently proposed concentric figure of eight layout, which, due to intrinsic cancellation of external noise, enables measurements in high noise environments. We identify conditions under which good resolution performance is achieved. To verify our approach, we also perform inversions of synthetic data for selected layouts.
A good sketch is better than a long speech: evaluate delinquency risk through real-time video analysis
Authors: Chang Xiangyu , Dai Lili , Feng Lingbing , Han Jianlei , Shi Jing , Zhang Bohui
Published: December 2024

This article proposes an innovative method to assess borrowers’ creditworthiness in consumer credit markets by conducting machine-learning-based analyses on real-time video information that records borrowers’ behavior during the loan application process. We find that the extent of borrowers’ micro-facial expressions of happiness is negatively associated with loan delinquency likelihood, while the degree of fear expressions is positively associated with delinquency risk. These results are consistent with two economic channels relating to the adequacy and uncertainty of borrowers’ future income, drawn from the extant psychology and economics literature. Our study provides important practical implications for fintech lenders and policymakers.
Unveiling the neural dynamics of the theory of mind: a fMRI study on belief processing phases
Authors: Golec-Staśkiewicz Karolina , Wojciechowski Jakub , Haman Maciej , Wolak Tomasz , Wysocka Joanna , Pluta Agnieszka
Published: December 2024

Theory of mind (ToM), the ability to interpret others’ behaviors in terms of mental states, has been extensively studied through the False-Belief Task (FBT). However, limited research exists regarding the distinction between different phases of FBT, suggesting that they are subserved by separate neural mechanisms. Further inquiry into this matter seems crucial for deepening our knowledge of the neurocognitive basis of mental-state processing. Therefore, we employed functional Magnetic Resonance Imaging (fMRI) to examine neural responses and functional connectivity within the core network for ToM across phases of the FBT, which was administered to 61 healthy adults during scanning. The region-of-interest analysis revealed heightened responses of the temporoparietal junction (TPJ) during and increased activation of medial prefrontal cortex (mPFC) during the outcome phase. Negative connectivity between these regions was observed during belief-formation. Unlike the TPJ, mPFC responded similarly to conditions that require belief reasoning and to control conditions that do not entail tracking mental states. Our results indicate a functional dissociation within the core network for ToM. While the TPJ is possibly engaged in coding beliefs, the mPFC shows no such specificity. These findings advance our understanding of the unique roles of the TPJ and mPFC in mental-state processing.