bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early drivers of clonal hematopoiesis shape the evolutionary trajectories ofde novoacute myeloid leukemia
Authors: Chow Ryan D. , Velu Priya , Deihimi Safoora , Belman Jonathan , Youn Angela , Shah Nisargbhai , Luger Selina M. , Carroll Martin P. , Morrissette Jennifer , Bowman Robert L 
Published: September 2024

ABSTRACTMutations commonly found in AML such asDNMT3A,TET2andASXL1can be found in the peripheral blood of otherwise healthy adults – a phenomenon referred to as clonal hematopoiesis (CH). These mutations are thought to represent the earliest genetic events in the evolution of AML. Genomic studies on samples acquired at diagnosis, remission, and at relapse have demonstrated significant stability of CH mutations following induction chemotherapy. Meanwhile, later mutations in genes such asNPM1andFLT3, have been shown to contract at remission and in the case ofFLT3often are absent at relapse. We sought to understand how early CH mutations influence subsequent evolutionary trajectories throughout remission and relapse in response to induction chemotherapy. Here, we assembled a retrospective cohort of patients diagnosed withde novoAML at our institution that underwent genomic sequencing at diagnosis as well as at the time of remission and/or relapse (total n = 182 patients). Corroborating prior studies,FLT3andNPM1mutations were generally eliminated at the time of cytologic complete remission but subsequently reemerged upon relapse, whereasDNMT3A,TET2andASXL1mutations often persisted through remission. Early CH-related mutations exhibited distinct constellations of co-occurring genetic alterations, withNPM1andFLT3mutations enriched inDNMT3AmutAML, whileCBLandSRSF2mutations were enriched inTET2mutandASXL1mutAML, respectively. In the case ofNPM1andFLT3mutations, these differences vanished at the time of complete remission yet readily reemerged upon relapse, indicating the reproducible nature of these genetic interactions. Thus, early CH-associated mutations that precede malignant transformation subsequently shape the evolutionary trajectories of AML through diagnosis, therapy, and relapse.Key PointsDNMT3A,TET2andASXL1mutations persist through AML-directed therapyDistinct CH-related mutations shape the evolutionary trajectories of AML from diagnosis through relapse.
Expanding the spectrum of white matter abnormalities in Wolfram syndrome: A retrospective review
Authors: Simo Justin , Lugar Heather M. , Miller Elka , Wilf-Yarkoni Adi , Goldberg Yael , Kocaağa Ayça , Ito Shoichi , Cocozza Sirio , Frontino Giulio , Baldoli Cristina , Benbachir Aziz , Ashton Catherine , Rouleau Guy , Hershey Tamara , Nadjar Yann , La Piana Roberta 
Published: September 2024

AbstractBackground and ObjectivesWolfram syndrome (WFS) is a genetic disorder mainly caused by pathogenic variants in theWFS1gene. It is characterized clinically by optic atrophy (OA), diabetes mellitus (DM), sensorineural hearing loss (SNHL), diabetes insipidus (DI), and variable neurological/psychiatric symptoms. WFS typically manifests before age 20 and progresses into adulthood. Classical neuroradiological features include cerebellar and/or brainstem atrophy as well as white matter abnormalities ranging from small, ovoid lesions to diffuse, symmetrical changes along the visual pathway. Following the identification of multifocal, progressive white matter abnormalities that prompted the consideration of multiple sclerosis (MS) in two molecularly confirmed WFS subjects, we sought to verify whether MS-like lesions constitute a novel WFS-associated MRI pattern.MethodsWe conducted an international multicenter retrospective study of the clinical, genetic, and radiological data from 17 unrelated WFS subjects.ResultsSeven subjects (7/17; 41%) showed at least one focal white matter lesion evocative of MS. Among these seven, three fulfilled the McDonald radiological criteria of dissemination in space and time, suggesting an inflammatory demyelinating process. All subjects reviewed in the study had at least one of the classical WFS MRI features.ConclusionsOur report expands the WFS spectrum of white matter involvement to include progressive, seemingly inflammatory demyelinating lesions. While we cannot exclude the possibility of a WFS-MS dual diagnosis in some cases, the role ofWFS1in myelination suggests a selective white matter vulnerability in WFS. Our findings suggest that follow up MRI should be recommended to adult subjects with WFS. Further identification and longitudinal study of adult WFS subjects is required to confirm whether a WFS molecular diagnosis confers susceptibility to the development of MS.
Clustering of pulmonary tuberculosis in Ethiopia: repeated population-based symptom screening
Authors: Banti Abiot Bezabeh , Datiko Daniel Gemechu , Winje Brita Askeland , Hinderaker Sven Gudmund , Heldal Einar , Dangisso Mesay Hailu 
Published: September 2024

AbstractObjectiveA “Cluster” is an area with a higher occurrence of tuberculosis than would be expected in an average random distribution of that area. Tuberculosis clustering is commonly reported in Ethiopia, but most studies rely on registered data, which may miss patients who do not visit health facilities or those who attend but are not identified as having tuberculosis. This makes the detection of actual clusters challenging. This study analysed the clustering of pulmonary tuberculosis and associated risk factors using symptom-based population screening in Dale, Ethiopia.DesgignA prospective population-based cohort study.SettingAll households in 383 enumeration areas were visited three times over 1 year period, at four-month intervals.ParticipantsIndividuals with pulmonary tuberculosis aged ≥15 years with demographic, socioeconomic, clinical, and geographic data residing in 383 enumeration areas (i.e., the lowest unit/village in the kebele, each with approximately 600 residents).Outcome measuresPulmonary tuberculosis (i.e., bacteriologically confirmed by sputum microscopy, GeneXpert or cluture plus clinically diagnosed pulmonary tuberculosis) and pulmonary tuberculosis clustering.ResultsWe identified pulmonary tuberculosis clustering in 45 out of the 383 enumeration areas. During the first round of screening, 39 enumeration areas showed pulmonary tuberculosis clustering, compared to only three enumeration areas in the second and third rounds. Our multilevel analysis found that enumeration areas with clusters were located farther from the health centres than other enumeration areas. No other determinants examined were associated with clustering.ConclusionsThe distribution of pulmonary tuberculosis was clustered in enumeration areas distant from the health centres. Routine systematic community screening using existing health infrastructure with Health extension workers may be costly but through targeted screening they can identify and refer persons with TB symptoms more quickly for diagnosis and treatment, thereby decreasing the duration of disease transmission and contributing to the reduction of TB burden.Stregths and limiations of this studyThe study applied a three-round total household symptom screening strategy to identify undiagnosed as well as diagnosed tuberculosis cases, and hence identify real clusters.Health extension workers actively involved the entire population in screening, benefitting from their trust and familiarity with the community.The study also sought for risk factors for clustering that may require attention from public health practices at the lowest community level.Smear microscopy will due to relatively low sensitivity always miss some cases of tuberculosis.
Highly versatile small virus-encoded proteins in cellular membranes: A structural perspective on how proteins’ inherent conformational plasticity couples with host membranes’ properties to control cellular processes
Authors: Delkhosh Arvin Saffarian , Hadadianpour Elaheh , Islam Md Majharul , Georgieva Elka R. 
Published: September 2024

AbstractWe investigated several small viral proteins that reside and function in cellular membranes, which belong to the viroporin family because they assemble into ion-conducting oligomers. However, despite forming similar oligomeric structures with analogous functions, these proteins have diverse amino acid sequences. In particular, the amino acid compositions of the proposed channel-forming transmembrane (TM) helices are vastly different—some contain residues (e.g., His, Trp, Asp, Ser) that could facilitate cation transport. Still, other voroporins’ TM helices encompass exclusively hydrophobic residues; therefore, it is difficult to explain their channels’ activity, unless other mechanisms (e.g., involving a negative lipid headgroup) take place. For this study, we selected the M2, Vpu, E, p13II, p7, and 2B proteins from the influenza A, HIV-1, human T-cell leukemia, hepatitis C, and picorna viruses, respectively. We discuss the current knowledge of these proteins’ structures as well as remaining questions about a more comprehensive understanding of their structures, conformational dynamics, and function. Finally, we outline strategies to utilize a multi-prong structural approach to overcome current deficiencies in the knowledge about these proteins.HighlightsSmall viral proteins encoded homo-oligomerize and function in cellular membranes as ion channelsThese proteins were combined in the family of viroporinsDespite the similarity in their oligomeric structures and functions, these proteins have vastly different primary structuresIt is imperative to understand how proteins with no homology in their primary structures fulfill similar functions for diverse virusesThere is a need for a multi-prong structural approach to explain the structure, conformational dynamics, and function of these proteins
MHCII deletion in mouse myeloid cells alters T-cell subset frequencies and inflammatory responses to alpha-synuclein pathology and epigenetic analysis of human monocytes reveals genotype-as well as disease-dependent differentially accessible chromatin regions in theHLAlocus
Authors: Kline EM , Jernigan JE , Scharer CD , Maurer J , Hicks SL , Herrick MK , Wallings RL , Kelly SD , Chang J , Menees KB , McFarland NR , Boss JM , Tansey MG , Joers V 
Published: September 2024

AbstractMajor histocompatibility complex class II (MHCII) molecules are antigen presentation proteins and increased in post-mortem Parkinson’s disease (PD) brain. Attempts to decrease MHCII expression have led to neuroprotection in PD mouse models. Our group reported that a SNP atrs3129882in the MHCII gene Human leukocyte Antigen (HLA) DRA is associated with increased MHCII transcripts and surface protein and increased risk for late-onset idiopathic PD. We therefore hypothesized that decreased MHCII may mitigate dopaminergic degeneration. During an ongoing α-synuclein lesion, mice with MHCII deletion in systemic and brain innate immune cells (LysMCre+I-Abfl/fl) displayed brain T cell repertoire shifts and greater preservation of the dopaminergic phenotype in nigrostriatal terminals. Next, we investigated a human cohort to characterize the immunophenotype of subjects with and without the high-riskGGgenotype at thers3129882SNP. We confirmed that the high-riskGGgenotype is associated with peripheral changes in MHCII inducibility, frequency of CD4+ T cells, and differentially accessible chromatin regions within the MHCII locus. Although our mouse studies indicate that myeloid MHCII deletion coinciding with an intact adaptive immune system is insufficient to fully protect dopamine neurons from α-synuclein-induced degeneration, our data are consistent with the overwhelming evidence implicating antigen presentation in PD pathophysiology.
Responses of grapevine cells to physiological doses of ethanol, among which induced resistance to heat stress
Authors: Diot Alice , Madignier Guillaume , Di Valentin Olivia , Djari Anis , Maza Elie , Chen Yi , Blanchet Simon , Chervin Christian 
Published: September 2024

AbstractGrapevine naturally endures stresses like heat, drought, and hypoxia. A recent study showed very low oxygen levels inside grape berries, linked to ethanol content. Other studies have established the link between ethanol and tolerance to various stresses: heat stress, drought, and high salinity. The causes of such a tolerance are not well understood. In our study, three-week-old Gamay calli,Vitis vinifera, were characterised for their endogenous oxygen levels and endogenous ethanol concentration. Subsequently, a transcriptomic study of these cells was conducted, 6 and 24 hours after treatment with 1 mM ethanol. After 6 hours, ethanol addition led to 386 differentially expressed genes, with a notable upregulation of genes related to heat response, especially small Heat Shock Proteins (sHSPs). Further experiments showed that ethanol priming in grape cells or inArabidopsisseedlings reduced pigment and electrolyte leakage under heat stress, respectively. This study supports the idea that ethanol priming helps protect plants against heat stress and provides a valuable RNA-seq dataset for further research into the underlying mechanisms, sHSPs playing a potentially crucial role in this adaptive response.
Prevalence of heritable symbionts in the Parisian Bedbugs (Hemiptera: Cimicidae)
Authors: Cagatay Naciye Sena , Akhoundi Mohammad , Izri Arezki , Brun Sophie , Hurst Gregory D. D. 
Published: September 2024

AbstractLike many insects, the biology of bedbugs is impacted by a range of partner heritable microbes. Three maternally inherited symbionts are recognised,Wolbachia(an obligate partner),Symbiopectobacteriumpurcelli strainSyClec andCa. Tisiphiasp. (facultative symbionts typically present in some but not all individuals). Past work had examined these heritable microbes from established laboratory lines, but not from broader field samples. We therefore deployed targeted endpoint PCR assays to determine the symbiont infection status for 50 bedbugs collected from 10 districts of Paris during the 2023 outbreak. All three symbionts were found to be broadly present acrossC. lectulariussamples with theSymbiopectobacterium-Ca. Tisiphia-Wolbachiatriple infection most commonly observed. A minority of individuals lacked either one or both facultative symbionts. Five mtDNA haplotypes were observed across the COI barcode region. Triple infections were found in all mtDNA haplotypes, indicating symbiont infection had been circulating over a protracted period of time. We conclude that the Parisian bedbug outbreak was one in which the host’s secondary symbionts were present at high frequency coinfections. Thus, facultative symbionts are an important but uncharacterized component of bedbug populations.
Red flags useful to screen for suspect cancer in patients with low back pain: a scoping review protocol
Authors: Notarangelo Gianluca , Giovannico Giuseppe , Bruno Francesco , Milella Claudia , Mourad Firas , Maselli Filippo 
Published: September 2024

ABSTRACTLow back pain (LBP) is defined as pain and discomfort occurring under the costal arch and above the inferior gluteal folds, with or without leg pain. The most common type of low back pain is “non-specific low back pain”. It is defined as such because there is no specific pathology that can be the cause. Instead, “specific low back pain” is caused by diseases such as infections, tumors, osteoporosis, ankylosing spondylitis, fractures, inflammatory processes, radicular syndromes, cauda equina syndrome, etc. It is the most common musculoskeletal disorder in the world and the most cause of disability.Most low back pain is benign in nature and specific diagnoses are uncommon; however in some specific cases this clinical presentation of signs and symptoms could hide much more serious conditions. The second most frequent serious pathology, after fracture, that may initially appears as low back pain is tumor pathology (0.2% and 7.0%), condition that turns out to be so dangerous as to be the second leading cause of death in the world according to the WHO.Red flags are signs and symptoms that raise suspicion of the presence of serious diseases; these are clinical aspects of alert that can justify referral to the doctor/specialist and can contraindicate physiotherapy treatment.Clinicians must therefore be able to recognize clinical presentations that are potentially dangerous to the patient that may require further evaluation or emergency referral. Failure to immediately recognize these conditions could lead to incorrect diagnoses resulting in worsening outcomes over time. The tools that will guide the clinician in recognizing the red flags in low back pain are a through medical history and a complete physical examination.Currently we have very little clarity and agreement in the literature about the Red Flags that should be better investigated, a scoping review is strongly required and corresponded to the objectives of this project.
Multinational attitudes towards AI in healthcare and diagnostics among hospital patients
Authors: Busch Felix , Hoffmann Lena , Xu Lina , Zhang Longjiang , Hu Bin , García-Juárez Ignacio , Toapanta-Yanchapaxi Liz N , Gorelik Natalia , Gorelik Valérie , Rodriguez-Granillo Gaston A , Ferrarotti Carlos , Cuong Nguyen N , Thi Chau AP , Tuncel Murat , Kaya Gürsan , Solis-Barquero Sergio M , Mendez Avila Maria C , Ivanova Nevena G , Kitamura Felipe C , Hayama Karina YI , Puntunet Bates Monserrat L , Torres Pedro Iturralde , Ortiz-Prado Esteban , Izquierdo-Condoy Juan S , Schwarz Gilbert M , Hofstaetter Jochen G , Hide Michihiro , Takeda Konagi , Perić Barbara , Pilko Gašper , Thulesius Hans O , Lindow Thomas A , Kolawole Israel K , Olatoke Samuel Adegboyega , Grzybowski Andrzej , Corlateanu Alexandru , Iaconi Oana-Simina , Li Ting , Domitrz Izabela , Kępczyńska Katarzyna , Mihalčin Matúš , Fašaneková Lenka , Zatoński Tomasz , Fułek Katarzyna , Molnár András , Maihoub Stefani , Gama Zenewton A da Silva , Saba Luca , Sountoulides Petros , Makowski Marcus R , Aerts Hugo JWL , Adams Lisa C , Bressem Keno K ,   COMFORT consortium
Published: September 2024

AbstractThe successful implementation of artificial intelligence (AI) in healthcare is dependent upon the acceptance of this technology by key stakeholders, particularly patients, who are the primary beneficiaries of AI-driven outcomes. This international, multicenter, cross-sectional study assessed the attitudes of hospital patients towards AI in healthcare across 43 countries. A total of 13806 patients at 74 hospitals were surveyed between February and November 2023, with 64.8% from the Global North and 35.2% from the Global South. The findings indicate a predominantly favorable general view of AI in healthcare, with 57.6% of respondents expressing a positive attitude. However, attitudes exhibited notable variation based on demographic characteristics, health status, and technological literacy. Female respondents and those with poorer health status exhibited fewer positive attitudes towards AI use in medicine. Conversely, higher levels of AI knowledge and frequent use of technology devices were associated with more positive attitudes. It is noteworthy that less than half of the participants expressed positive attitudes regarding all items pertaining to trust in AI. The lowest level of trust was observed for the accuracy of AI in providing information regarding treatment responses. Patients exhibited a strong preference for explainable AI and physician-led decision-making, even if it meant slightly compromised accuracy. This large-scale, multinational study provides a comprehensive perspective on patient attitudes towards AI in healthcare across six continents. Findings suggest a need for tailored AI implementation strategies that consider patient demographics, health status, and preferences for explainable AI and physician oversight. All study data has been made publicly available to encourage replication and further investigation.
The Use of Conversational Agents in Self-Management: A Retrospective Analysis
Authors: Colakoglu Selahattin , Durmus Mustafa , Polat Zeynep Pelin , Yildiz Asli , Sezgin Emre 
Published: September 2024

AbstractBackgroundUnderstanding user engagement with conversational agents (CAs) in mobile health apps is crucial for improving sustained usage. We analyzed CA interactions in a mobile health app to identify usage patterns and potential barriers.Materials and MethodsRetrospective data from 100,571 active users of the Albert Health app in 2022 were analyzed. Interactions with CA were categorized by demographics (gender and age), interaction type (health information, medication-related, clinical parameters, and non-clinical), and engagement method (text, voice). Descriptive statistics were used to identify trends and patterns in app usage.ResultsOut of the active users, 19,051 (18.9%) engaged with the CA. The majority were female (61%), with 43% aged 30-45 years and 23% older than 45 years. The analysis showed that 94.5% engaged in general health management, while 5.3% used disease-specific programs. Average usage per user was highest in cardiovascular and respiratory diseases. Interaction types varied, with health information and medication-related interactions. The varied messaging behavior suggests different user engagement levels, with some users seeking quick information and others engaging more deeply for health management. Engagement was high initially but decreased over time.DiscussionThis study provides insights into user interactions with a healthcare CA, highlighting a preference for general health management and diverse usage patterns. The significant number of single-session users indicates potential barriers to sustained engagement, highlighting the need for strategies to enhance user experience and retention. Future research should investigate the CA’s performance, effectiveness and extend observations to broader healthcare contexts by using large language models.