bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of a thermal correction method for infrared spectroscopy: preparation for the future observations of the Martian moons Phobos and Deimos with the MIRS instrument
Authors: David Gaël , Delbo Marco , Barucci Maria Antonietta , Merlin Frédéric , Fraeman Abigail A , Fornasier Sonia , Poggiali Giovanni , Beck Pierre , Leyrat Cédric
Published: September 2024

The MIRS (MMX InfraRed Spectrometer) infrared spectrometer is part of the scientific payload of JAXA’s (Japanese Space Agency) Martian Moon eXploration (MMX) mission. From the reflected sunlight by the planetary surfaces, MIRS will provide information on the Mars atmosphere and the mineralogy and chemistry of its moons. Spectra carried out by the instrument (0.9–3.6 $\mu$m) include the thermal emission from the surface, which needs to be modelled and removed to extract the compositional information. In this study, to find an efficient and rapid way to thermally correct infrared data, we developed a simple thermal emission correction based on blackbody fits, and quantify its relative error. To test the method, we generated synthetic spectra of Phobos by using a thermophysical model. We found that the method can produce reflectance spectra with only a few per cent errors, although some undercorrection of the thermal contribution is observed. Compositional information may still be retrieved through the position of absorption bands, despite the thermal emission correction can leave some uncertainties in its strength. We conclude that the method could be used for a first and quick analysis for interpretation of the MIRS data. We also applied our thermal correction methodology to real CRISM (Compact Reconnaissance Imaging Spectrometer for Mars) observations of Phobos. The method looks reliable with a satisfactory removal of the thermal contribution, confirms the presence of an absorption band centred around 2.8 $\mu$m, and reveals an apparent absorption at 3.2 $\mu$m. However, we are not able to confirm the reality of the 3.2 $\mu$m band at this stage, because of the presence of an artefact in CRISM data.
The Interaction Jigsaw: investigating star formation in interacting galaxies
Authors: Robin T , Kartha Sreeja S , Akhil Krishna R , Krishnan Ujjwal , Mathew Blesson , Cysil T B , Patra Narendra Nath , Shridharan B
Published: September 2024

Interaction between galaxies plays a pivotal role in their evolution. Ongoing star formation in spiral galaxies can be affected by these processes. Interacting galaxy pairs provide an opportunity to study these effects. We select a sample of interacting galaxies in field environments at various interaction stages and are nearly face-on and chose galaxy pairs NGC 2207/IC 2163, NGC 4017/4016 (ARP 305), and NGC 7753/7752 (ARP 86). We use the UltraViolet Imaging Telescope (UVIT) onboard AstroSat to characterize the star-forming regions in the galaxy with a superior resolution of $\mathrm{\sim 1.4\,\,\mathrm{ arcsec}}$. We identified and characterized star-forming regions in the UVIT images of the sample and correlated them with the neutral hydrogen (H i) distribution. We detected localized regions of enhancement in star formation surface density ($\mathrm{\Sigma _{SFR}}$) and distortions in the sample of galaxies. We found this consistent with the distribution of H i in the galaxy. These are possible evidence of past and ongoing interactions affecting the star formation properties in the galaxies. We then conducted a study to understand whether the observed enhancements hold true for a wider sample of interacting galaxies. We observe a moderate enhancement in the star formation rate (SFR) with the interaction class, with a maximum of 1.8 being in the merger class of galaxies. We studied the SFR enhancement for the main galaxies in our sample as a function of pair mass ratio and pair separation. We observe a strong anticorrelation between the SFR enhancement and pair mass ratio and no linear correlation between the enhancement and pair separation. This suggests that the enhancement in interaction-induced star formation may be more strongly influenced by the pair mass ratios, rather than the pair separation. We also infer that the pair separation can possibly act as a limiting parameter for the SFR enhancement.
The association of azole antifungals with overall survival in patients with non-small cell lung cancer receiving immune checkpoint inhibitors
Authors: Sebastian Nikhil T , Stokes William A , Behera Madhusmita , Jiang Renjian , Gutman David A , Huang Zhonglu , Burns Abigail , Sukhatme Vidula , Lowe Michael C , Ramalingam Suresh S , Sukhatme Vikas P , Moghanaki Drew
Published: September 2024

Background

Preclinical data suggest antifungal azole derivatives have antitumor efficacy that may modulate response to immune checkpoint inhibitors (ICIs). We aimed to evaluate the association of azole drugs with overall survival (OS) in a population of patients with non-small cell lung cancer (NSCLC) treated with ICI within the Veterans Health Administration (VHA).

Methods

In this retrospective study, the VA Corporate Data Warehouse was queried for patients diagnosed with NSCLC and treated with ICI from 2010 to 2018. Concomitant oral azole use was defined as dispensation by a VA pharmacy within 90 days of the first ICI infusion. Patients who received azole after 30 days were excluded from the analysis to mitigate immortal time bias. OS was measured from the start of ICI. Cox regression and propensity score matching were used to adjust for confounders.

Results

We identified 3413 patients with NSCLC receiving ICI; 324 (9.5%) were exposed to concomitant azoles. As a group, azole use was not associated with OS (hazard ratio [HR] = 0.96; 95% CI, 0.84-1.09; P = .51). After stratification by azole type, clotrimazole had an association with better OS on univariable (HR = 0.75; 95% CI, 0.59-0.96; P = .024) and multivariable analysis (HR = 0.71; 95% CI, 0.56-0.91; P = .007). Propensity score matching of patients who received clotrimazole vs no azole yielded 101 patients per matched cohort. Clotrimazole was associated with improved OS, although this did not meet the threshold for statistical significance (HR = 0.74; 0.54-1.01; P = .058).

Conclusion

This observational study demonstrated an association between clotrimazole and OS among patients with advanced NSCLC receiving ICI. These findings build upon preclinical evidence and support further investigation into the potential for clotrimazole as a repurposed FDA drug to improve cancer outcomes.
No difference in reproductive investment or success across urban and rural breeding pairs in an urban-adapted songbird
Authors: Guindre-Parker Sarah , Acosta Arianna , Bourque Cole , Cook Amberlee , Corimanya Joanna , Kaplan Rachel , Kilgour Denyelle A V , Linkous Courtney R , Ross Michelle , Smith Trinity , Titus Careyjo
Published: September 2024

Species classified as “urban-adapters” are often assumed to thrive in cities because they are commonly found across the urbanization gradient. However, urban-living populations of many urban-adapted species have been found to have lower reproductive success relative to their rural counterparts. Sturnus vulgaris (European Starling) is a common urban-adapted species found across most of the globe. While S. vulgaris have lowered reproductive success in urban areas in their native range, less is known about how urbanization impacts reproduction in their invasive ranges. We tested for differences in reproductive investment and success across urban and rural S. vulgaris populations in Georgia, which is part of their North American invasive range. We found few differences in reproductive output for urban vs. rural S. vulgaris—clutch size, egg mass, egg volume, incubation behavior, provisioning rates, brooding behavior, and nestling wing chord were all similar across S. vulgaris populations from more urban and more rural study sites. Although urban birds produced a higher number of hatchlings and rural birds produced young in higher body condition, neither of these factors influenced reproductive success because the number of fledglings produced were similar for urban and rural breeding S. vulgaris. Overall, S. vulgaris in their invasive range performed similarly well in more urban vs. more rural habitats. Future work should explore whether urbanization affects other components of fitness in starlings (e.g., adult survival).
Growing the image: Generative AI and the medium of gardening
Authors: Young Nick , Terrone Enrico
Published: September 2024

In this paper, we argue that Midjourney—a generative AI program that transforms text prompts into images—should be understood not as an agent or a tool, but as a new type of artistic medium. We first examine the view of Midjourney as an agent, considering whether it could be seen as an artist or co-author. This perspective proves unsatisfactory, as Midjourney lacks intentionality and mental states. We then explore the notion of Midjourney as a tool, highlighting its unpredictability and the limited fine-grained control users have over its outputs, which sets it apart from traditional artistic tools. We propose that creating images with Midjourney parallels a gardener's interaction with natura naturans—nature's autonomous generative processes. Similarly, Midjourney acts as machina naturans, where users engage with its dynamic recalcitrance to influence, but not fully control, the creative process. This approach presents Midjourney as an artistic medium shaped by its inherent unpredictability.
Aging increases lightness of grass-fed beef
Authors: Wicks Jordan C , Wivell Alexis L , Beline Mariane , Zumbaugh Morgan D , Bodmer Jocelyn S , Yen Con-Ning , Wilson Thomas B , Greiner Scott P , Johnson Sally E , Shi Tim H , Silva Saulo L , Gerrard David E
Published: September 2024

Grass-fed beef is becoming increasingly popular and is expected to be a $14 billion industry by 2024. Even so, grass-fed beef is typically darker in appearance than that of conventional grain-fed beef. Aging has been shown to improve lean color (L*, a*) of dark-cutting beef however little work has focused on aging as it relates to improving the lean color of grass-fed beef. Therefore, the aim of this study was to evaluate the effect of dry aging on grass-fed beef compared to varying lengths of grain-feeding. Thirty commercial Angus crossbred steers were randomly assigned to either pasture finishing (CON), short (SF), or long fed (LF) programs. The SF and LF treatments ranged from 90 to 114 d (average: 98 d) and 118 to 134 d (average: 125 d) on ad libitum high concentrate feeding, respectively. Cattle were randomly identified from each treatment group and harvested over a consecutive 3-wk span. Carcass evaluation and longissimus lumborum samples were collected 24 h postmortem. Carcasses were aged for 21 d, and steaks were collected on 1-, 3-, 7-, 10-, 14-, and 21-d postharvest, and objective color was evaluated following 1 h bloom. Our data show color (L*, a*, b*) was improved with aging regardless of treatment. However, grass-fed (CON) showed the greatest improvement in both lightness (L*) and redness (a*) ultimately making grass-fed comparable to that of grain-fed beef by day 21. These data argue that dry-aging grass-fed beef improves color development similar to that of grain-fed beef.
The microbiome of continuous wheat rotations: minor shifts in bacterial and archaeal communities but a source for functionally active plant-beneficial bacteria
Authors: Braun-Kiewnick Andrea , Giongo Adriana , Zamberlan Priscilla Mena , Pluta Patrick , Koch Heinz-Josef , Kage Henning , Smalla Kornelia , Babin Doreen
Published: September 2024

Continuous wheat cropping often leads to yield decline, with suspected causes including increased pathogen susceptibility, decreased root growth, or low nutrient use efficiency, though the exact causes remain unknown. Here, we investigated soil and root-associated bacterial and archaeal communities in wheat under rotation versus continuous cultivation, monitored fungal pathogen presence, and used beneficial bacteria to mitigate Gaeumannomyces tritici (Ggt) symptoms in greenhouse experiments. Sampling was conducted at two field sites with different soil textures over two years and at two plant developmental stages, capturing site-specific and seasonal fluctuations. By cultivation, 767 bacterial isolates were screened for plant-beneficial traits. Amplicon sequencing revealed minor effects on community structure due to wheat rotational position but pronounced effects related to site, year, and microhabitat. Rhizoplane isolates with plant-beneficial traits were mainly Flavobacterium, Microbacterium, Pedobacter, Pseudomonas, Stenotrophomonas, and Variovorax. Continuous wheat rotations showed the highest proportion of bacteria with fungal antagonistic potential, indicating plant roots’ recruitment of beneficial bacteria. Introducing Ggt in the greenhouse experiment altered the bacterial and archaeal community, confirming field study results and demonstrating that applying beneficial bacteria early in the season at the seedling stage can control Ggt and improve plant growth. This study highlights the dynamic nature of wheat's below-ground bacterial and archaeal community, influenced by soil type, season, and microhabitat, with wheat rotation playing a minor role. In addition, it confirms the potential of selected Bacillus and Pseudomonas isolates, whether used individually or in consortia, for microbe-assisted mitigation of yield decline in intensive wheat production.
Arbuscular mycorrhizal fungi modify temporal virus accumulation and distribution in different grapevine tissues
Authors: Gaši Emanuel , Radić Tomislav , Gambino Giorgio , Čarija Mate , Matić Frano , Balestrini Raffaella , Hančević Katarina
Published: September 2024

Arbuscular mycorrhizal fungi (AMF) have been shown to improve plant host tolerance to biotic stresses. However, AMF-mediated protection against virus diseases have been highly variable and poorly investigated in perennial crops. In this study, we investigated the influence of AMF on virus concentration and distribution in grapevine coinfected with three common viruses, grapevine rupestris stem-pitting associated virus (GRSPaV), solely or in coinfection with grapevine leafroll-associated virus 3 (GLRaV-3) and grapevine Pinot Gris virus (GPGV). Two different types of AMF inocula were used: i) Rhizophagus irregularis (Ri) and ii) R. irregularis, Funneliformis mosseae and F. caledonium (Mix). Sampling for quantitative RT-PCR (RT-qPCR) was performed three times throughout one-year period in four distinct grapevine tissues for the assessment of GRSPaV concentration in AMF-inoculated grapevine. AMF influence on GRSPaV was the most significant in the first sampling, two months post inoculation, with virus accumulating predominantly in roots. Simultaneously, GRSPaV concentration in young grapevine leaves was low, possibly due to modified source-sink dynamics. Quantification of GLRaV-3 and GPGV was performed in coinfected grapevine in the third sampling. After a year, both viruses exhibit accumulation in the roots of mycorrhizal plants. However, GLRaV-3 displayed accentuated accumulation and GPGV decrease in foliage, indicating differential effect on the virus in coinfected grapevine. Regarding AMF symbiosis, generally Mix inoculum induced more pronounced virus concentration changes than Ri alone. In summary, this study shows differences in virus load of AMF-inoculated and AMF-free grapevine and adds nuance to the complex multitrophic interactions that are shaping grapevines health.
Age-adjusted Baseline Neck Disability Index Values
Authors: Lipson Patricia , Bansal Aiyush , Leveque Jean-Christophe , Kumar Rakesh , Fujii Takeshi , Nemani Venu M. , Louie Philip K.
Published: September 2024

Study Design.

Survey-based, prospective study.

Objective.

Identify age-adjusted baseline neck disability index (NDI) values in the American population.

Background.

The NDI is the most widely used tool for assessing self-rated disability in patients with neck pain. Establishing baseline NDI values can aid in understanding the clinical impact of cervical spine pathologies and treatment interventions.

Materials and Methods.

An internet-based survey was distributed using the Connect (TM) platform powered by CloudResearch. Based on the latest U.S. census, this survey was designed to engage a demographically representative sample of the U.S. adult population. We captured 699 individuals, aiming for 100 people per each 10-year age group between 18 and 89. Participants scored their disability using the NDI survey. Mean NDI scores stratified by age group and sex were calculated for each cohort.

Results.

A total of 699 participants were included with 352 (50.4%) males and 347 (49.6%) females and an age distribution closely aligning with national demographics. The overall mean NDI for the combined age groups was 16.5 with a 95% CI of 15.5 to 17.5. The 18 to 29 age group had the lowest mean NDI of 12.3 (95% CI: 10.4, 14.2). Mean NDI scores increased until the 60 to 69 age group with a mean of 20.1 (95% CI: 17.3, 23.0) with women having a mean NDI of 22.2 (95% CI: 18.8, 25.7) compared with men with 15.4 (95% CI: 10.3, 20.4). Mean NDI scores decreased in the 70 to 79 and 80 to 89 age groups.

Conclusion.

This is the first study to assess age-adjusted baseline values of NDI in the U.S. population. Our findings demonstrate a disproportionate distribution of disability ratings across age groups. These data are important for health care professionals as it provides age and sex-specific levels of disability.

Level of Evidence.

Level III.
Percutaneous coronary intervention vs. medical therapy in patients on dialysis with coronary artery disease in China
Authors: Xie Enmin , Wu Yaxin , Ye Zixiang , He Yong , Zeng Hesong , Luo Jianfang , Chen Mulei , Pang Wenyue , Xu Yanmin , Gao Chuanyu , Guo Xiaogang , Cai Lin , Ji Qingwei , Yang Yining , Wu Di , Yuan Yiqiang , Wan Jing , Ma Yuliang , Zhang Jun , Du Zhimin , Yang Qing , Cheng Jinsong , Ding Chunhua , Ma Xiang , Yin Chunlin , Fan Zeyuan , Tang Qiang , Li Yue , Sun Lihua , Lu Chengzhi , Chi Jufang , Yao Zhuhua , Gao Yanxiang , Yu Changan , Ren Jingyi , Zheng Jingang
Published: September 2024

Background:

The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China.

Methods:

This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences.

Results:

Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [n = 278] vs. 43.7% [n = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45–0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs. 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82–2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses.

Conclusion:

This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
The first magnetic resonance imaging compatible 3D printer
Authors: Antoniou Anastasia , Evripidou Nikolas , Giannakou Marinos , Damianou Christakis
Published: September 2024

Background:

The current study presents the development of a magnetic resonance imaging (MRI)-compatible silicone-based 3D printer capable of producing patient-specific implants within MRI scanners.

Methods:

The printing device incorporates 3 piezoelectrically-actuated linear motion stages assigned for navigating a custom-made silicone extruder to develop the desired 3D model based on preoperative MRI scans of the damaged anatomy. The structural components were manufactured on a rapid prototyping machine with thermoplastic and compactly assembled utilizing non-magnetic materials to ensure fit and safe functioning of the system within the MRI bore.

Results:

The printing system was successfully integrated with a high-field MRI scanner and operated safely while maintaining sufficient imaging quality. The robotic motion mechanism exhibited excellent repeatability and achieved submillimeter accuracy, demonstrating its capability for precise positioning of the extruder.

Conclusion:

The proposed 3D printer may hold promise as valuable tool for personalized tissue reconstruction by real-time printing with biocompatible silicone on the MRI table. However, challenges such as prolonged processing times and related high costs will possibly hinder its adoption in clinical practice.
Effectiveness of low-dose rivaroxaban in preventing recurrent major adverse cardiovascular events in coronary artery disease: a systematic review and meta-analysis of randomized controlled trials
Authors: Al Hennawi Hussam , Khan Muhammad Khuzzaim , Rasheed Faisal , Rathi Sushma , Ali Mirha , Ali Abraish , Asghar Zoha , Pasha Khadija , Ashraf Muhammad Talal , Klugherz Bruce
Published: September 2024

Introduction

Despite advancements in coronary artery disease (CAD) management, major adverse cardiovascular events persist. Vitamin K antagonists and direct oral anticoagulants present bleeding risks. Low-dose rivaroxaban (2.5 mg) is approved by the European Society of Cardiology and the US Food and Drug Administration for CAD. The survival advantage and risk-benefit profile of combining low-dose rivaroxaban with aspirin for CAD patients remain uncertain. This meta-analysis aims to compare the efficacy of low-dose rivaroxaban plus aspirin versus aspirin monotherapy in CAD patients.

Methods

We systematically searched databases for randomized controlled trials exploring low-dose rivaroxaban with aspirin in CAD patients. Of the 6220 studies screened, five met the inclusion criteria. Primary outcomes included myocardial infarction, stroke, major bleeding events, and all-cause mortality. The analysis employed a fixed-effects model, calculating hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

Five randomized controlled trials involving 41,351 participants were included. Rivaroxaban (2.5 mg) significantly reduced all-cause mortality (HR, 0.88; 95% CI, 0.81–0.95; P = 0.002), myocardial infarction (HR, 0.81; 95% CI, 0.70–0.94; P = 0.006), and stroke (HR, 0.61; 95% CI, 0.49–0.76; P < 0.00001) compared to aspirin alone. However, it increased major bleeding risk (HR, 1.66; 95% CI, 1.40–1.97; P < 0.01). Meta-regression revealed no dose-dependent impact on all-cause mortality.

Conclusion

Low-dose rivaroxaban demonstrates survival benefits and reduces myocardial infarction and stroke risks in CAD patients, albeit with an increased risk of major bleeding. Consideration of patient bleeding risk is crucial when adding rivaroxaban to antiplatelet therapy. Further research is warranted to compare its effectiveness and safety with dual antiplatelet therapy or P2Y12 inhibitors.
Hematopoietic cell transplantation for inborn errors of immunity: an update on approaches, outcomes and innovations
Authors: Williams Olatundun
Published: September 2024

Purpose of review

Allogeneic hematopoietic cell transplantation (HCT) is a curative option for many for inborn errors of immunity (IEI). This review highlights recent progress in the field of HCT for IEI.

Recent findings

Alternative donor transplantation continues to expand donor options for patients with IEI. Reduced intensity and reduced toxicity conditioning approaches are being investigated and optimized. Immunomodulatory bridging therapies are yielding impressive progress in outcomes for primary immune regulatory disorders (PIRD) but require further study in prospective trials. Single-institution, multicenter and consortium studies have improved our understanding of factors that affect overall outcomes in IEI and outcomes in Wiskott–Aldrich syndrome (WAS), chronic granulomatous disease (CGD) and PIRD in particular. Data show that second HCT offers a viable chance of cure to some IEI patients. Late effects in IEI HCT survivors are being better characterized. Preclinical studies of chemo(radiation)-free HCT strategies hold promise for decreasing HCT toxicity.

Improvements in our understanding of HCT donor choice, conditioning regimen, immunomodulatory bridging therapies, diagnostic and post-HCT surveillance testing and late effects continue to yield advancements in the field of HCT for IEI.
Integrated Stepped Alcohol Treatment With Contingency Management for Unhealthy Alcohol Use Among People With HIV: A Randomized Controlled Trial
Authors: Edelman E. Jennifer , Dziura James , Deng Yanhong , DePhilippis Dominick , Ferguson Tekeda , Brown Sheldon , Marconi Vincent C. , Goetz Matthew Bidwell , Rodriguez-Barradas Maria C. , Simberkoff Michael S. , Molina Patricia E. , Weintrob Amy C. , Maisto Stephen A. , Paris Manuel , Justice Amy C. , Bryant Kendall J. , Fiellin David A.
Published: September 2024

Background:

We examined the impact of integrated stepped alcohol treatment with contingency management (ISAT + CM) on alcohol abstinence among people with HIV (PWH) and unhealthy alcohol use.

Methods:

In this multisite 24-week trial, we randomized PWH reporting untreated unhealthy alcohol use and with phosphatidylethanol (PEth) >20 ng/mL to receive ISAT+CM or treatment as usual (TAU). Intervention: Step 1: Social worker-delivered CM; Step 2: Addiction physician management plus motivational enhancement therapy. Participants were advanced to step 2 at week 12 if they lacked evidence of abstinence over the prior 21 days. TAU: Health handout, and for those who met criteria for alcohol use disorder, a referral to substance use treatment. Primary outcome: self-reported abstinence for the past 21 days at week 24.

Results:

We enrolled 120 PWH between January 5, 2018, and March 1, 2022. Mean age was 59 years, 96% were men, and 83% were Black. Eight percent were lost to follow-up. In the ISAT+CM group, 87% were advanced to Step 2. The posterior mean proportion of participants with self-reported abstinence at 24 weeks was higher among those randomized to ISAT+CM [posterior mean proportion 9% (95% credible interval [CrI]: 0%–33%)] compared with TAU [posterior mean proportion 0.3% (95% CrI: 0%–4%)] [posterior mean treatment effect 9%, (95% CrI: 0%–32%)], the posterior probability of TAU being superior to ISAT + CM was <0.0001.

Discussion:

ISAT + CM delivered in HIV clinics modestly increased self-reported 3-week abstinence among PWH. Our findings indicate a need for more effective treatments to promote abstinence and a potential role for ISAT + CM for reductions in alcohol use.

Trial registration:

Clinicaltrials.gov (NCT03089320).
Ancestry and somatic profile predict acral melanoma origin and prognosis
Authors: Basurto-Lozada Patricia , Vázquez-Cruz Martha Estefania , Molina-Aguilar Christian , Jiang Amanda , Deacon Dekker C. , Cerrato-Izaguirre Dennis , Simonin-Wilmer Irving , Arriaga-González Fernanda G. , Contreras-Ramírez Kenya L. , Dawson Eric T. , Wong-Ramirez J. Rene C. , Ramos-Galguera Johana Itzel , Álvarez-Cano Alethia , García-Ortega Dorian Y. , García-Salinas Omar Isaac , Hidalgo-Miranda Alfredo , Cisneros-Villanueva Mireya , Martínez-Said Héctor , Arends Mark J. , Ferreira Ingrid , Tullett Mark , Olvera-León Rebeca , van der Weyden Louise , del Castillo Velasco Herrera Martín , Roldán-Marín Rodrigo , Vidaurri de la Cruz Helena , Tavares-de-la-Paz Luis Alberto , Hinojosa-Ugarte Diego , Belote Rachel L. , Bishop D. Timothy , Díaz-Gay Marcos , Alexandrov Ludmil B. , Sánchez-Pérez Yesennia , In Gino K. , White Richard M. , Possik Patrícia A. , Judson-Torres Robert L. , Adams David J. , Robles-Espinoza Carla Daniela
Published: September 2024

Acral melanoma, which is not ultraviolet (UV)-associated, is the most common type of melanoma in several low- and middle-income countries including Mexico. Latin American samples are significantly underrepresented in global cancer genomics studies, which directly affects patients in these regions as it is known that cancer risk and incidence may be influenced by ancestry and environmental exposures. To address this, here we characterise the genome and transcriptome of 128 acral melanoma tumours from 96 Mexican patients, a population notable because of its genetic admixture. Compared with other studies of melanoma, we found fewer frequent mutations in classical driver genes such asBRAF,NRASorNF1. While most patients had predominantly Amerindian genetic ancestry, those with higher European ancestry had increased frequency ofBRAFmutations and a lower number of structural variants. TheseBRAF-mutated tumours have a transcriptional profile similar to cutaneous non-volar melanocytes, suggesting that acral melanomas in these patients may arise from a distinct cell of origin compared to other tumours arising in these locations.KITmutations were found in a subset of these tumours, and transcriptional profiling defined three expression clusters; these characteristics were associated with overall survival. We highlight novel low-frequency drivers, such asSPHKAP, which correlate with a distinct genomic profile and clinical characteristics. Our study enhances knowledge of this understudied disease and underscores the importance of including samples from diverse ancestries in cancer genomics studies.
Correlates of Self-Sampling Willingness for HPV-DNA Testing among Medically Underserved Rural Kenyan Women: A Mixed Methods Study
Authors: Chepkorir Joyline , Perrin Nancy , Kivuti-Bitok Lucy , Gallo Joseph J , Gross Deborah , Anderson Jean , Reyolds Nancy R , Wyche Susan , Kibet Hillary , Kipkuri Vincent , Cherotich Anastacia , Han Hae-Ra
Published: September 2024

Introduction

Cervical cancer is the leading cause of cancer-related deaths among Sub-Saharan African women, particularly in rural areas where screening rates are lower due to limited access to highly sensitive tests. This study aimed to investigate factors that might influence rural Kenyan women’s willingness to self-collect samples for HPV-DNA testing.

Methods

This study utilized data from a mixed-methods study in Bomet and Kericho Counties, including survey responses from 174 women and semi-structured interviews with a subset of 21 participants. Logistic regression was used to analyze quantitative data and theoretical thematic analysis for qualitative data.

Results

The surveyed women had a mean age of 45.2 years, were mainly uninsured (76%) and from low-income households (88.4%). Most participants had heard of cervical cancer (83.2%), yet only 6.4% had ever been screened. However, 76.9% expressed willingness to self-collect samples for HPV-DNA testing. Factors significantly associated with increased self-sampling willingness were cervical cancer awareness (OR=3.49, 95% CI=1.50-8.11), having health workers (OR=1.88, CI=1.23-2.86) and the news media (radio and television) (OR=2.63, CI=1.27-5.48) as primary sources of health information, and ever hearing about cervical cancer from the news media (OR=2.43, CI=1.07-5.51). Conversely, high cervical cancer stigma (OR=0.71, CI=0.57-0.88) and longer travel time of 30 to 120 minutes to the nearest health facility (OR=0.44, CI=0.20-0.93) were associated with decreased willingness. Interview data corroborated these findings.

Conclusions

Cervical cancer screening uptake is notably low among rural Kenyan women in Bomet and Kericho Counties. Sample self-collection for HPV-DNA testing appears widely acceptable. A comprehensive approach involving educational outreach, health worker recommendation, and mass media campaigns could enhance cervical cancer screening via self- sampling, potentially reducing the burden of cervical cancer. Future research should employ implementation science methodologies to explore cervical cancer screening uptake via self- sampling, to inform population-based implementation strategies in Kenya.
A novel alpha-synuclein G14R missense variant is associated with atypical neuropathological features
Authors: Brücke Christof , Al-Azzani Mohammed , Ramalingam Nagendran , Ramón Maria , Sousa Rita L. , Buratti Fiamma , Zech Michael , Sicking Kevin , Amaral Leslie , Gelpi Ellen , Chandran Aswathy , Agarwal Aishwarya , Chaves Susana R. , Fernández Claudio O. , Dettmer Ulf , Lautenschläger Janin , Zweckstetter Markus , Busnadiego Ruben Fernandez , Zimprich Alexander , Outeiro Tiago Fleming
Published: September 2024

Background

Parkinson’s disease (PD) affects millions of people worldwide, but only 5–10% of patients suffer from a monogenic form of the disease with Mendelian inheritance.SNCA,the gene encoding for the protein alpha-synuclein (aSyn), was the first to be associated with familial forms of PD and, since then, several missense variants and multiplications of theSNCAgene have been established as rare causes of autosomal dominant forms of PD.

Aim and methods

A patient carrying aSyn missense mutation and his family members were studied. We present the clinical features, genetic testing - whole exome sequencing (WES), and neuropathological findings. The functional consequences of this aSyn variant were extensively investigated using biochemical, biophysical, and cellular assays.

Results

The patient exhibited a complex neurodegenerative disease that included generalized myocloni, bradykinesia, dystonia of the left arm and apraxia. WES identified a novel heterozygousSNCAvariant (cDNA 40G>A; protein G14R). Neuropathological examination showed extensive atypical aSyn pathology with frontotemporal lobar degeneration (FTLD) and nigral degeneration pattern with abundant ring-like neuronal inclusions, and few oligodendroglial inclusions. Sanger sequencing confirmed theSNCAvariant in the healthy, elderly parent of the patient patient suggesting incomplete penetrance. NMR studies suggest that the G14R mutation induces a local structural alteration in aSyn, and lower thioflavin T binding in in vitro fibrillization assays. Interestingly, the G14R aSyn fibers display different fibrillar morphologies as revealed by cryo-electron microscopy. Cellular studies of the G14R variant revealed increased inclusion formation, enhanced membrane association, and impaired dynamic reversibility of serine-129 phosphorylation.

The atypical neuropathological features observed, which are reminiscent of those observed for the G51D aSyn variant, suggest a causal role of theSNCAvariant with a distinct clinical and pathological phenotype, which is further supported by the properties of the mutant aSyn, compatible with the strain hypothesis of proteinopathies.
Exploring a roadmap to achieving tobacco endgame in sub-Saharan Africa: A qualitative study among stakeholders from 12 countries
Authors: Egbe Catherine O. , Ngobese Senamile P. , Khan Arshima , Gwambe Siphesihle , Ngcobo Zinhle P. , Bialous Stella A.
Published: September 2024

Introduction

Tobacco endgame seeks to bring an end to tobacco use or drastically reduce prevalence to <5%. Discussions about tobacco endgame and the possible strategies to achieve this goal in Sub-Saharan African (SSA) are sparse. This study aimed to explore SSA tobacco control stakeholders’ perspectives about tobacco endgame and ascertain what strategies they perceive to be suitable for the region to achieve this.

Methods

This was a qualitative study involving a purposive sample of 29 stakeholders interviewed via online platforms guided by a semi-structured interview schedule. Stakeholders were from academia, civil society, and government departments in 12 SSA countries. Interviews were conducted in English or French, transcribed verbatim (those in French were translated to English) and thematically analyzed with the aid of NVIVO v12.

Results

There is support for the adoption of tobacco endgame in SSA by tobacco control stakeholders in in the region due to the impact tobacco has on health, the environment and economy. Proposed endgame approaches for SSA were recommended to be Afrocentric which must be sensitive to cultural and regional dynamics. Stakeholders believed that the success of endgame strategies depends on political will, multi-sectoral collaboration, availability of resources, buy-in from the public and tobacco industry monitoring. Suggested endgame strategies were categorized into 5 themes: Product-focused (less addictive tobacco and regulation of novel products); User-focused (smoke-free generation, cessations supports and use of sports); Market/supply-focused (licensing of sellers, increase in taxes, control of illicit trade and alternative income for farmers); Institutional structure-focused (tobacco industry monitoring and regulation) and legislation implementation-focused (effective implementation of international treaties aimed at lowering tobacco use prevalence).

Conclusion

There is support for a tobacco endgame in SSA. Collaboration from various departments/ministries, and support from government and the public would be needed to make tobacco endgame a reality in SSA.

Key Highlights

Discussion on how to end tobacco use (endgame) in Sub-Saharan African (SSA) is sparse.

Tobacco control stakeholders in SSA are supportive of tobacco endgame for the region.

Afrocentric endgame strategies sensitive to culture and countries’ peculiarities are needed.

User, product and supply focused, as well as institutional and legislation focused strategies have been proposed.

Proposed endgame strategies must include alternative income for farmers and cessation support.

Support from SSA governments and the public, and tobacco industry monitoring are needed for successful implementation of tobacco endgame in SSA.
Cascaded Multimodal Deep Learning in the Differential Diagnosis, Progression Prediction, and Staging of Alzheimer’s and Frontotemporal Dementia
Authors: Guarnier Gianmarco , Reinelt Janis , Molloy Eóin N. , Mihai Paul Glad , Einaliyan Pegah , Valk Sofie , Modestino Augusta , Ugolini Matteo , Mueller Karsten , Wu Qiong , Babayan Anahit , Castellaro Marco , Villringer Arno , Scherf Nico , Thierbach Konstantin , Schroeter Matthias L. ,   the Alzheimer’s Disease Neuroimaging Initiative ageing the Australian Imaging Biomarkers and Lifestyle flagship study of Initiative and the Frontotemporal Lobar Degeneration Neuroimaging
Published: September 2024

Dementia syndromes are complex sequelae whose multifaceted nature poses significant challenges in the diagnosis, prognosis, and treatment of patients. Despite the availability of large open-source data fueling a wealth of promising research, effective translation of preclinical findings to clinical practice remains difficult. This barrier is largely due to the complexity of unstructured and disparate preclinical and clinical data, which traditional analytical methods struggle to handle. Novel analytical techniques involving Deep Learning (DL), however, are gaining significant traction in this regard. Here, we have investigated the potential of a cascaded multimodal DL-based system (TelDem), assessing the ability to integrate and analyze a large, heterogeneous dataset (n=7159 patients), applied to three clinically relevant use cases. Using a Cascaded Multi-Modal Mixing Transformer (CMT), we assessed TelDem’s validity and (using a Cross Modal Fusion Norm - CMFN) model explainability in (i) differential diagnosis between healthy individuals, AD, and three sub-types of frontotemporal lobar degeneration (ii) disease staging from healthy cognition to mild cognitive impairment (MCI) and AD, and (iii) predicting progression from MCI to AD. Our findings show that the CMT enhances diagnostic and prognostic accuracy when incorporating multimodal data compared to unimodal modeling and that cerebrospinal fluid (CSF) biomarkers play a key role in accurate model decision making. These results reinforce the power of DL technology in tapping deeper into already existing data, thereby accelerating preclinical dementia research by utilizing clinically relevant information to disentangle complex dementia pathophysiology.
Early menarche and childbirth accelerate aging-related outcomes and age-related diseases: Evidence for antagonistic pleiotropy in humans
Authors: Xiang Yifan , Tanwar Vineeta , Singh Parminder , La Follette Lizellen , Narayan Vikram , Kapahi Pankaj
Published: September 2024

Aging can be understood as a consequence of the declining force of natural selection with age. Consistent with this, the antagonistic pleiotropy theory of aging proposes that aging arises from trade-offs that favor early growth and reproduction. However, evidence supporting antagonistic pleiotropy in humans remains limited. Using Mendelian Randomization (MR), we demonstrated that later ages of menarche or first childbirth were genetically associated with longer parental lifespan, decreased frailty index, slower epigenetic aging, later menopause, and reduced facial aging. Moreover, later menarche or first childbirth were also genetically associated with a lower risk of several age-related diseases, including late-onset Alzheimer’s disease (LOAD), type 2 diabetes, heart disease, essential hypertension, and chronic obstructive pulmonary disease (COPD). We validated the associations between the age of menarche, childbirth, and the number of childbirths with several age-related outcomes in the UK Biobank by conducting regression analysis of nearly 200,000 subjects. Our results demonstrated that menarche before the age 11 and childbirth before 21 significantly accelerated the risk of several diseases, and almost doubled the risk for diabetes, heart failure, and quadrupled the risk of obesity, supporting the antagonistic pleiotropy theory. We identified 126 significant single nucleotide polymorphisms (SNPs) that influenced age-related outcomes, some of which were involved in known longevity pathways, including IGF1, growth hormone, AMPK, and mTOR signaling. Our study also identified higher BMI as a mediating factor in causing the increased risk of certain diseases, such as type 2 diabetes and heart failure, in women with early menarche or early pregnancy, emphasizing the importance of the thrifty gene hypothesis in explaining in part the mechanisms behind antagonistic pleiotropy. Our study highlights the complex relationship between genetic legacies and modern diseases, emphasizing the need for gender-sensitive healthcare strategies that consider the unique connections between female reproductive health and aging.
Informing an Intervention to Improve Access to Community Pharmacist-Provided Injectable Naltrexone for Formerly Incarcerated Individuals in Wisconsin
Authors: Chladek Jason S. , Chui Michelle A.
Published: September 2024

In Wisconsin, opioid use disorder (OUD) is highly prevalent among individuals impacted by the criminal justice system. Medications for opioid use disorder (MOUD), including injectable naltrexone, are crucial for treating OUD and especially important for individuals transitioning out of correctional facilities and back into the community. Unfortunately, few formerly incarcerated individuals are able to access MOUD upon community reentry, remaining at high risk of overdose and rearrest. Community pharmacists are a promising resource for providing injectable naltrexone to formerly incarcerated individuals using this treatment option, but are underutilized during reentry planning and by formerly incarcerated individuals upon release. This is due, in large part, to several barriers that exist across the socioecological scale. Accordingly, this study utilized a participatory design process to inform an intervention that address these barriers and improves access to community pharmacist-provided injectable naltrexone for formerly incarcerated individuals upon community reentry. Three iterative focus groups were conducted with five community pharmacists who have experience providing injectable naltrexone and treating formerly incarcerated patients. The goals of each focus group were to: 1) discuss perceptions of existing barriers and prioritize barriers to be addressed, 2) discuss and rank potential interventions to address the prioritized barriers, and 3) discuss components and anticipated challenges related to the prioritized intervention. Focus groups were analyzed via deductive content analysis using a priori categories. Based on discussions of perceived impact and feasibility, the participants prioritized two barriers to be addressed: lack of awareness of community pharmacist-provided injectable naltrexone services and lack of interagency collaboration among primary care clinics, community pharmacies, and correctional facilities. The final intervention included pharmacist-led educational meetings with correctional providers and reentry staff. Several intervention components and anticipated challenges were also identified. Next steps include developing, implementing, and evaluating the efficacy of the intervention on improving access to community pharmacist-provided injectable naltrexone for formerly incarcerated individuals.
Scaling-Up the Impact of Teledermoscopy on the Early Detection of Skin Melanoma using Convolutional Neural Networks with Mobile Apps
Authors: Tyagi Tejasvi , Vempati Swati Mathur , Upadhyay Kshitiz
Published: September 2024

Advances in the cloud technology for secured distributed data storage, modern techniques for machine learning (ML), and access to large populations through mobile apps provide a unique opportunity for the healthcare industry professionals in the areas of early screening and medical diagnostics for certain diseases. This research study demonstrates the potential of ML using convolutional neural networks (CNN) for medical diagnostics of skin melanoma. Specifically, a comparison is presented between a shallow CNN (3-layers) with Resnet50 (50-layers) to classify open datasets of skin melanoma images as malignant or benign. Various ML performance metrics such as accuracy, recall, precision and receiver operating characteristic (ROC) are presented to recommend a deep learning model for the mobile app. Also, a novel framework is proposed for the scalability and adoption of ML-based medical diagnostics by large masses as a mobile app running on data-secure cloud platform. Using the open datasets, it is shown that skin cancer can be accurately diagnosed with a mobile phone app while maintaining patient privacy and data security.