bluuebunny/crossref_metadata_2025 huggingface dataset:
Decrypting the phylogenetics history of EGF-CFC proteins Cripto and Cryptic
Authors: Shylo Natalia A. , Trainor Paul A.
Published: September 2024

EGF-CFC proteins are obligate coreceptors for Nodal signaling and are thus required for gastrulation and left-right patterning. Species with multiple family members show evidence of specialization. For example, mouseCriptois required for gastrulation, whereasCrypticis involved in left-right patterning. However, the members of the family across model organisms have little sequence conservation beyond the EGF-CFC domain, posing challenges for determining their evolutionary history and functional conservation. In this study we outline the evolutionary history of the EGF-CFC family of proteins. We traced theEGF-CFCgene family from a single gene in the deuterostome ancestor through its expansion and functional specialization in tetrapods, and subsequent gene loss and translocation in eutherian mammals. MouseCriptoandCryptic, zebrafishTdgf1,and all threeXenopus EGF-CFCgenes (Tdgf1,Tdgf1.2andCripto.3) and are all descendants of the ancestralTdgf1gene. We propose that subsequent to the family expansion in tetrapods,Tdgf1B(Xenopus Tdgf1.2) acquired specialization in the left-right patterning cascade, and after its translocation in eutherians to a different chromosomal location,Cfc1/Cryptichas maintained that specialization.
Immune targets for schistosomiasis control identified by a genome-wide association study of East African snail vectors
Authors: Pennance Tom , Tennessen Jacob A , Spaan Johannie M , McQuistan Tammie , Ogara George , Rawago Fredrick , Andiego Kennedy , Mulonga Boaz , Odhiambo Meredith , Mutuku Martin W , Mkoji Gerald M , Loker Eric S , Odiere Maurice R , Steinauer Michelle L
Published: September 2024

Schistosomiasis, afflicting >260 million people worldwide, could be controlled by preventing infection of freshwater snail vectors. Intestinal schistosomiasis, caused by Schistosoma mansoni, occurs predominantly in Sub-Saharan Africa and is vectored by Biomphalaria sudanica and related Biomphalaria species. Despite their importance in transmission, very little genomic work has been initiated in African snails, thus hindering development of novel control strategies. To identify genetic factors influencing snail resistance to schistosomes, we performed a pooled genome-wide association study (pooled-GWAS) on the offspring of B. sudanica collected from a persistent hotspot of schistosomiasis in Lake Victoria, Kenya, and exposed to sympatric S. mansoni. Results of the pooled-GWAS were used to develop an amplicon panel to validate candidate loci by genotyping individual snails. This validation revealed two previously uncharacterized, evolutionarily dynamic regions, SudRes1 and SudRes2, that were significantly associated with resistance. SudRes1 includes receptor-like protein tyrosine phosphatases and SudRes2 includes a class of leucine-rich repeat-containing G-protein coupled receptors, both comprising diverse extracellular binding domains, suggesting roles in pathogen recognition. No loci previously tied to schistosome resistance in other snail species showed any association with compatibility suggesting that loci involved in the resistance of African vectors differ from those of neotropical vectors. Beyond these two loci, snail ancestry was strongly correlated with schistosome compatibility, indicating the importance of population structure on transmission dynamics and infection risk. These results provide the first detail of the innate immune system of the major schistosome vector, B. sudanica, informing future studies aimed at predicting and manipulating vector competence.
Clinical Application of Large Language Models for Breast Conditions: A Systematic Review
Authors: Cheung Billy Ho Hung , Poon Karen Gwyn , Lai Cheuk Fai , Lam Ka Chun , Co Michael , Kwong Ava
Published: September 2024

Background

The application of artificial intelligence (AI) like Large Language Models (LLM) into the healthcare system has been a frequently discussed topic in recent years.

Materials and Methods

We conducted a systemic review on primary studies about the applications of LLM in breast conditions. The studies are then categorized into their respective domains, namely diagnosis, management recommendations and communication for patients.

Results

The diagnostic accuracy ranged from 74.3% to 99.6% across different investigation modalities. The concordance of management recommendations ranged from 50% to 70% while the prognostic evaluation of breast cancer patients of distant recurrence showed an accuracy of 75% to 88%. In regards to patient communication, it is revealed that 18-30% of the references used by the LLM were irrelevant.

Conclusion

This study highlights the potential benefits of LLM in strengthening patient communication, diagnose and management of patients with breast conditions. With standardized protocol and guideline to minimize potential risks, LLM can be a valuable tool to support future clinicians in the field of breast management.
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

Mutations 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 Points

DNMT3A,TET2andASXL1mutations persist through AML-directed therapy

Distinct 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

Background and Objectives

Wolfram 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.

Methods

We conducted an international multicenter retrospective study of the clinical, genetic, and radiological data from 17 unrelated WFS subjects.

Results

Seven 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.

Conclusions

Our 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

Objective

A “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.

Desgign

A prospective population-based cohort study.

Setting

All households in 383 enumeration areas were visited three times over 1 year period, at four-month intervals.

Participants

Individuals 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 measures

Pulmonary tuberculosis (i.e., bacteriologically confirmed by sputum microscopy, GeneXpert or cluture plus clinically diagnosed pulmonary tuberculosis) and pulmonary tuberculosis clustering.

Results

We 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.

Conclusions

The 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 study

The 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

We 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.

Highlights

Small viral proteins encoded homo-oligomerize and function in cellular membranes as ion channels

These proteins were combined in the family of viroporins

Despite the similarity in their oligomeric structures and functions, these proteins have vastly different primary structures

It is imperative to understand how proteins with no homology in their primary structures fulfill similar functions for diverse viruses

There 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

Major 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

Grapevine 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.
Evidence for transient, uncoupled power and functional connectivity dynamics
Authors: Huang Rukuang , Gohil Chetan , Woolrich Mark
Published: September 2024

There is growing interest in studying the temporal structure in brain network activity, in particular, dynamic functional connectivity (FC), which has been linked in several studies with cognition, demographics and disease states. The sliding window approach is one of the most common approaches to compute dynamic FC. However it cannot detect cognitively relevant and transient temporal changes at the time scales of fast cognition, i.e. on the order 100 milliseconds, which can be identified with model-based methods such as HMM (Hidden Markov Model) and DyNeMo (Dynamic Network Modes) using electrophysiology. These new methods provide time-varying estimates of the "power" (i.e. variance) and of the functional connectivity of the brain activity, under the assumption that they share the same dynamics. But there is no principled basis for this assumption. In this work, we propose Multi-dynamic Network Modes (M-DyNeMo), an extension to DyNeMo, that allows for the possibility that the power and the FC networks have different dynamics. Using this new method on magnetoencephalography (MEG) data, we show intriguingly that the dynamics of the power and the FC networks are uncoupled. Using a (visual) task MEG dataset, we also show that the power and FC network dynamics are modulated by the task, such that the coupling in their dynamics changes significantly during task. This new method reveals novel insights into evoked network responses and ongoing activity that previous methods fail to capture, challenging the assumption that power and FC share the same dynamics.
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

Like 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

Low 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

The 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

Background

Understanding 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 Methods

Retrospective 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.

Results

Out 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.

Discussion

This 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.
Predicting thoracic aortic dissection in a diverse biobank using a polygenic risk score
Authors: DePaolo John , Zamirpour Siavash , Abramowitz Sarah , Biagetti Gina , Judy Renae , Beeche Cameron , Duda Jeffrey , Gee James , Witschey Walter R. , Chirinos Julio A. , Goel Nicholas J. , Desai Nimesh , Szeto Wilson Y. , Guo Dongchuan , Milewicz Dianna M. , Levin Michael G. , Pirruccello James P. , Damrauer Scott M.
Published: September 2024

Background

Thoracic aortic dissection is a life-threatening condition that often occurs in the presence of aortic dilation. Despite a known association between ascending aortic diameter (AscAoD) and dissection risk, predicting dissection risk remains challenging.

Objectives

Determine whether common variant genetics can be used to improve identification of individuals most at risk for dissection.

Methods

A genome wide association study (GWAS)-by-subtraction was performed to characterize the diameter-independent genetics of thoracic aortic dissection by subtracting a GWAS of aortic diameter (AoD) from a GWAS of thoracic aortic aneurysm and dissection (TAAD). A polygenic risk score (PRS) was calculated using the PRS-Continuous Shrinkage statistical package and evaluated for its ability to predict aortic dissection. The primary analytic cohort was Penn Medicine Biobank (PMBB) which comprises volunteers consenting to linkage of health records with biospecimens, including DNA which has undergone genome-wide genotyping; additional analyses were performed in the National Institutes of Health All of Us (AoU) cohort.

Results

We identified 43 significant genetic risk loci in our GWAS-by-subtraction and derived a “Dissection-PRS.” In the PMBB, the Dissection-PRS associated with an increased risk of prevalent dissection (odds ratio [OR]=2.13 per 1 standard deviation [sd] increase in Dissection-PRS, 95% confidence interval [CI] 1.91 to 2.39,P<0.001), These results were consistent when excluding individuals with pathogenic or likely pathogenic variants in established aortopathy genes. When adjusting for clinical risk factors including ascending aortic diameter, the association of the Dissection-PRS with prevalent dissection attenuated but remained significant (OR=1.62 per 1 sd increase in PRS, 95% CI 1.36 to 1.94,P<0.001). The addition of the PRS to a model containing age, sex, clinical risk factors, and ascending aortic diameter substantially improved model discrimination (base model area under the receiver operator characteristic curve [AUROC]=0.676, 95% CI 0.651 to 0.702; with addition of PRS AUROC=0.723, 95% CI 0.702 to 0.744). Analysis in AoU demonstrated similar findings.

Conclusions

A common-variant PRS can predict aortic dissection in a diverse population.
Investigating Gender Disparities in Ophthalmology Departments at Medical Schools in Japan
Authors: Iwasaki Akemi , Kato Naoko , Morita Yuka , Onouchi Hiromi , Itakura Mariko , Kunimi Keiko , Manabe Yoichi
Published: September 2024

This comprehensive study investigates the gender distribution of ophthalmologists in academic positions in Japanese medical schools. Data were collected from the websites of all ophthalmology departments and affiliated hospitals from November 1-15, 2023. Faculty gender was identified using first names and photographs, and where unclear, further verification was sought from the Ministry of Health, Labour, and Welfare or known contacts. The survey included 1,574 faculty members: 453 females (28.8%) and 1,121 males (71.2%). The representation of females varied significantly across different academic ranks: 9.9% were professors, 21.9% associate professors, 39.5% assistant professors, and 36.7% research associates. A significant gender disparity was observed, with males being 4.41 times more likely to become professors than females (p < 0.001). Conversely, females were more likely to hold research associate positions than males (Odds Ratio: 0.51, p < 0.001). This study highlights a male predominance in senior academic positions within ophthalmology departments in Japanese medical schools.
Wastewater testing during the South African 2022-2023 measles outbreak demonstrates the potential of environmental surveillance to support measles elimination
Authors: Ndlovu Nkosenhle , Mabasa Victor , Sankar Chenoa , Msomi Nosihle , Phalane Emmanuel , Singh Natasha , Gwala Sipho , Els Fiona , Macheke Mokgaetji , Maposa Sibonginkosi , Yousif Mukhlid , McCarthy Kerrigan M.
Published: September 2024

Background

Sensitive clinical surveillance and high vaccination coverage are required to meet the WHO 2030 measles elimination target. Whilst wastewater and environmental surveillance (WES) has proven usefulness in polio surveillance, it has not been applied to measles control. We describe the development of digital RT-PCR (RT-dPCR) for detection and quantification of measles virus (MeV) in wastewater, and application to retained concentrated samples obtained from 28 national sentinel SARS-CoV-2 wastewater surveillance sites and 19 localised collection points in a single province before, during and after a measles outbreak of over 2,000 laboratory-confirmed cases.

Methods

We validated a RT-dPCR assay incorporating WHO-recommended primers for detection and differentiation of wild-type and vaccine genotypes. We applied this to retained wastewater samples concentrated by ultrafiltration and stored at −20°C. We compared wastewater findings by district and epidemiological weeks with laboratory-confirmed measles case data obtained from national fever-rash surveillance for districts with adequate surveillance indicators (>2/100,000 non-measles cases)

Findings

Amongst 2,149 wastewater concentrates obtained between 16 February 2021 and 08 March 2024, we identified 43 (2%) samples containing MeV RNA in concentrations ranging from 2,04-6,11 genome copies/mL. MeV genotype A (vaccine strain) was co-detected in wastewater in 6 instances along with non-A (wild-type) genotypes. Comparison of wastewater and clinical fever-rash surveillance data by epidemiological week and district identified 27 district-time instances where at least one positive wastewater sample was identified, of which 14 (52%) districts reported at least one laboratory-confirmed clinical case in that same epidemiological week. Amongst districts with positive wastewater samples, wastewater surveillance detected MeV in 13/27 (48%) time-district pairs when clinical surveillance failed to detect cases. Amongst district-time instances where at least one laboratory-confirmed measles case was detected (N=127), MeV was detected in at least one wastewater sample collected in that same epidemiological week in 14 (11%) districts

Interpretation

Wastewater surveillance may be a useful complementary surveillance tool for identification of districts with ongoing measles circulation. MeV detection rates may be improved by real-time testing to limit RNA degradation and improved concentration and nucleic acid extraction processes. Ongoing wastewater surveillance for MeV should be conducted in order to understand the role of WES in measles control and elimination.

Funding

This work was funded by BMGF (INV-049271)
The Initiator Caspase Dronc Drives Compensatory Proliferation of Apoptosis-Resistant Cells During Epithelial Tissue Regeneration After Ionizing Radiation
Authors: Braun Tslil , Afgin Naama , Sapozhnikov Lena , Sivan Ehud , Bergmann Andreas , Baena-Lopez Luis Alberto , Yacobi-Sharon Keren , Arama Eli
Published: September 2024

Caspases, well-known for their role in executing apoptosis, also participate in various non-apoptotic processes. Despite this, their involvement in promoting compensatory proliferation - a key aspect of tissue regeneration following extensive cell death - has been a subject of ongoing ambiguity. In our study, we investigate compensatory proliferation in theDrosophilawing imaginal disc following ionizing radiation, a model epithelial tissue that has been a pioneering system for studying this regenerative response. Using a delayed genetic reporter to monitor the activity of the initiator caspase-2/9 ortholog, Dronc, we identified two populations of apoptosis-resistant epithelial cells involved in compensatory proliferation: those that activate Dronc (termed DARE cells) and those that do not (NARE cells). We show that DARE cells pass their apoptosis-resistance trait to their daughter cells, suggesting a molecular memory. We demonstrate that Dronc in DARE cells, but not the apoptosome adapter Dark and the effector caspases, promotes compensatory proliferation both within these cells and in NARE cells through a non-cell-autonomous mechanism. We found that Myo1D, an unconventional myosin interacting with Dronc, is essential for the survival of DARE cells by preventing the lethal activation of effector caspases and subsequent apoptosis. In contrast, Myo7A/Crinkled, another unconventional myosin that interacts with Dronc, promotes effector caspase activation in DARE cells. We demonstrate that the TNFR>JNK signaling pathway in DARE cells directly regulates their proliferation, which in turn influences NARE cell proliferation. Consequently, we show that maintaining proliferative homeostasis between DARE and NARE cells is vital for balanced tissue regeneration. Given the widespread use of ionizing irradiation in cancer treatment and prevention, our findings have potential implications for understanding treatment-resistant cells and cancer recurrence.
The fate of pollen in two morphologically contrasting buzz-pollinatedSolanumflowers
Authors: Vasquez-Castro Christian A. , Morel Elodie , Garcia-Simpson Bernardo , Vallejo-Marín Mario
Published: September 2024

Study premise

Pollen transfer efficiency (PTE) and pollen deposition patterns on a pollinator’s body significantly influence plant reproductive success. However, studies on pollen fates (i.e., the destination of pollen grains after being released) in animal-pollinated species, particularly those offering pollen as the sole reward, are limited. Here, we investigated pollen fates in two nectarless, buzz-pollinatedSolanumspecies with contrasting floral morphology.

Methods

We conducted experimental trials involving one pollen donor and four recipient flowers ofSolanum rostratumandS. dulcamara, using captiveBombus terrestrisas pollinator. After each trial, we assessed the amount of pollen remaining in the anthers, deposited on stigmas, placed on the pollinator, and falling to the ground. We then estimated pollen fates and PTE, and modelled their pollen deposition curves.

Key results

We found thatS. rostratumproduced more pollen but had a more restricted pollen dispensing schedule compared toS. dulcamara. Although PTE was similar between species (0.72% vs. 1.07%, forS. rostratumandS. dulcamara,respectively), pollen loss mainly occurred due to falling to the ground inS. rostratumand bee grooming inS. dulcamara, potentially explained by their different floral architectures. Both species exhibited a typical exponential decay pattern in pollen deposition, with the first visited flowers receiving the most outcross pollen.

Conclusions

Our results suggest that PTE in pollen-rewarding, buzz-pollinated species is quantitatively similar to that in nectar-rewarding flowers with single pollen units (PTE = 1-2%), and that different buzz- pollinated flower architectures achieve similar PTE although through different pollen-loss pathways.
Quantitative proteomic analysis of soil-grownBrassica napusresponses to nutrient deficiency
Authors: Grubb LE , Scandola S , Mehta D , Khodabocus I , Uhrig RG
Published: September 2024

ABSTRACT

Macronutrients such as nitrogen (N), phosphorus (P), potassium (K), and sulphur (S) are critical for plant growth and development. Field-grown canola (Brassica napusL.) is supplemented with fertilizers to maximize plant productivity, while deficiency in these nutrients can cause significant yield loss. A holistic understanding of the interplay between these nutrient deficiency responses in a single study and canola cultivar is thus far lacking, hindering efforts to increase the nutrient use efficiency of this important oil seed crop. To address this, we performed a comparative quantitative proteomic analysis of both shoot and root tissue harvested from soil-grown canola plants experiencing either nitrogen, phosphorus, potassium, or sulphur deficiency. Our data provide critically needed insights into the shared and distinct molecular responses to macronutrient deficiencies in canola. Importantly, we find more conserved responses to the four different nutrient deficiencies in canola roots, with more distinct proteome changes in aboveground tissue. Our results establish a foundation for a more comprehensive understanding of the shared and distinct nutrient deficiency response mechanisms of canola plants and pave the way for future breeding efforts.
Raffinose induces autophagy to promote plant growth
Authors: Magen Sahar , Daniel Sahar , Weiss Shahar , Factor David J. , Mursalimov Sergey , Soroka Yoram , Michaeli Simon , Avin-Wittenberg Tamar
Published: September 2024

Plant growth is governed by the integration of environmental cues and nutritional status. Under stress conditions, growth is usually attenuated in favor of stress response, creating a trade-off between growth and stress. Autophagy is a vital process in eukaryotes, maintaining cellular balance by degrading and recycling cellular components. It is triggered by various nutrient-deprivation conditions and both biotic and abiotic stresses in plants. Surprisingly, over-expressing autophagy-related genes across multiple plant species resulted in increased plant size, yield, and stress resistance, posing autophagy as a regulator of the stress-growth balance. Yet, the molecular mechanisms governing its induction remain partially understood.

In the current work, we identified raffinose-a plant-derived sugar known for its role in stress responses-as a novel plant autophagy inducer. Raffinose treatment resulted in increased biomass and yield in an autophagy-dependent manner in several plant species. We also show that raffinose activates autophagy through the SnRK1 kinase complex, independent of TOR signaling, and that raffinose treatment results in increased expression ofATG5andATG7. We also point to possible downstream candidates operating autophagy-related biomass accumulation. Our findings offer new perspectives on the role of autophagy in maintaining a balance between plant growth and stress responses, underscoring the significance of raffinose in its regulation.

SIGNIFICANCE STATEMENT

The intricate balance between plant growth and stress responses is crucial for agricultural productivity, particularly as climate change intensifies environmental stressors such as drought and extreme temperatures. Usually, there is a trade-off between growth and stress response. Autophagy—a cellular recycling process essential for maintaining cellular homeostasis—plays a pivotal role in this balance. Yet, the molecular mechanisms modulating it are partially understood. Raffinose treatment enhances biomass and yields in various plant species by inducing autophagy. By elucidating the molecular mechanisms of raffinose-mediated autophagy induction, our findings provide valuable insights into potential strategies for enhancing plant resilience against climate-induced stress.
A short note on the use of irreducible representations for tilted octahedra in perovskites
Authors: Glazer A. M.
Published: September 2024

It is pointed out that many authors are unaware that the particular choice of unit-cell origin determines the irreducible representations to which octahedral tilts in perovskites belong. Furthermore, a recommendation is made that the preferred option is with the origin at the B-cation site rather than that of the A site.
Substitutional/positional disorder of biguanide and guanylurea in the structure of a decavanadate complex [(Bg)(HV10O28
5−)]0.4[(HGU+)(V10O28
6−)]0.6(H2Met2+)2(H3O+)·8H2O
Authors: Chatkon Aungkana , Haller Kenneth J. , Haller Joseph P.
Published: September 2024

A hydrated salt of decavanadate containing diprotonated metforminium(2+) (H2Met2+), hydronium (H3O+) and either neutral biguanide (Bg) or monoprotonated guanylurea (HGU+) exhibits a previously seen complex charge-stabilized hydrogen-bonded network [Chatkon et al. (2022). Acta Cryst. B78, 798–808]. Charge balance is achieved in two ways through substitutional disorder: a 0.6 occupied HGU+ cation is paired with a V10O28
6− anion, and a 0.4 occupied neutral Bg molecule is paired with a HV10O28
5− anion, with the remaining charge in both cases balanced by two H2Met2+ dications and one H3O+ monocation. Bg/HGU+ moieties exhibit bifurcated N—H...O hydrogen bonding to the H3O+ cation and are substitutionally/positionally disordered along with the H3O+ cation about an inversion center. The HGU+ V10O28
6− synthon seen in the previous study occurs again. Bg exhibits bifurcated hydrogen bonding from two amino groups to two rows of cluster O atoms running diagonally across the equatorial plane of the HV10O28
5− anion with a return hydrogen bond from the cluster H atom to the imino N atom of the Bg. Thus, a Bg...cluster synthon similar to the HGU+...cluster synthon previously reported is found. The disordered moieties occupy spaces with excess volume in the 3-D network structure. Interestingly, when the crystallographic unit cell of the current compound, whose X-ray data was collected at 100 K, is compared with that of a previous compound exhibiting the same supramolecular framework, unit-cell parameter c does not shorten as a and b expectantly do because of the lower data collection temperature. The lack of contraction on unit-cell parameter c is possibly due to the supramolecular structure.
Competing institutional logics in healthcare organizations: theorising digitalism
Authors: Kjekshus Lars Erik , Bygstad Bendik
Published: September 2024

Purpose

The digitalisation of healthcare services has proven to be difficult, with numerous negative effects. We argue that the reason for the problem is not poor project management, but a clash of different institutional logics. The aim of this article is to explore, define and theorise the concept of digitalism, as a term for a new institutional logic in contrast to other, more known logics in organisations, such as managerialism and professionalism, to better understand processes of digitalisation.

Design/methodology/approach

We illustrate our arguments with a case study of a process of organizational development before and after the implementation of centralised large-scale IT systems at a large Norwegian hospital. Data was extracted from documents and observations from January 2015 to January 2016 during an organizational audit. In addition, a follow-up study was conducted in 2019 and 2024 by interviewing eight key personnel who were involved in the implementation process.

Findings

The implementation of a new digital health record in a Norwegian hospital is a process of social restructuring that involves new actors, logics and control systems. The process of digitalisation shows us how digitalism create tensions, diverges and merges with other institutional logics.

Practical implications

Understanding digitalism as a sensitising concept offers insights into how large-scale technology and organizations are tied together and can help to reduce organizational dysfunctionalities and improve the implementation of IT systems.

Originality/value

This study contributes to a new understanding of digitalisation processes and links an ongoing theoretical debate on the digitalisation of organizations with empirical findings.