bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfusion Camp Rwanda 2023: A train‐the‐trainer workshop establishing locally driven leadership in knowledge translation and sustainability in transfusion medicine education
Authors: Nizeyimana Francoise , Pendergrast Jacob , Ntegerejuwampayee Angelique , Lin Yulia , Kanyamuhunga Aimable , Gashaija Christopher , Masaisa Florence , Uzamukunda Claudine , Mutuyimana Grace , Ndicunguye Fabrice , Gaseminari Alexis , Mulindwa Bruce , Muyombo Thomas , Chargé Sophie , Skelton Teresa
Published: March 2024

Background and Objectives

Blood transfusion is performed daily in hospitals. Gaps exist between transfusion guidelines and day‐to‐day clinical care. These gaps are prevalent in resource‐limited settings due to scarce continuing medical education. Transfusion Camp Rwanda aims to bridge this gap by (1) delivering context‐appropriate up‐to‐date education, (2) teaching participants how to independently deliver a case‐based curriculum and (3) identifying strategies to promote change in transfusion practice in Rwanda.

Materials and Methods

In May 2023, a multidisciplinary team from Canada and Rwanda carried out a Transfusion Camp train‐the‐trainer workshop for clinicians from all five provinces in Rwanda. Participants attended in‐person lectures, seminars and workshop group discussions on the implementation of the Rwanda National Directives on Rational Use of Blood and Blood Components. Course feedback was based on the Kirkpatrick Model of Training and Evaluation.

Results

Fifty‐one physicians and laboratory technicians participated in the course. Confidence in caring for patients based on transfusion guidelines was self‐rated as ‘excellent’ by 23% of participants before and 77% after, while 84% reported they planned to teach Transfusion Camp to others and 100% responded that they will apply course content to clinical practice. Workshop groups recommended strategies to improve transfusion medicine practice in Rwanda in four domains: Communication, Institutional Approval, Practice Audits and Education.

Conclusion

Transfusion medicine education in Rwanda using a train‐the‐trainer approach was well‐received by participants and allowed for a more detailed understanding of the local medical and educational environment. These observations can inform the further expansion of the Transfusion Camp Rwanda project.
Machine-Learning Metacomputing for Materials Science Data
Authors: Steuben J. C. , Geltmacher A. B. , Rodriguez S. N. , Birnbaum A. J. , Graber B. D. , Rawlings A. K. , Iliopoulos A. P. , Michopoulos J. G.
Published: March 2024

Materials science requires the collection and analysis of great quantities of data. These data almost invariably require various post-acquisition computation to remove noise, classify observations, fit parametric models, or perform other operations. Recently developed machine-learning (ML) algorithms have demonstrated great capability for performing many of these operations, and often produce higher quality output than traditional methods. However, it has been widely observed that such algorithms often suffer from issues such as limited generalizability and the tendency to “over fit” to the input data. In order to address such issues, this work introduces a metacomputing framework capable of systematically selecting, tuning, and training the best available machine-learning model in order to process an input dataset. In addition, a unique “cross-training” methodology is used to incorporate underlying physics or multiphysics relationships into the structure of the resultant ML model. This metacomputing approach is demonstrated on four example problems: repairing “gaps” in a multiphysics dataset, improving the output of electron back-scatter detection crystallographic measurements, removing spurious artifacts from X-ray microtomography data, and identifying material constitutive relationships from tensile test data. The performance of the metacomputing framework on these disparate problems is discussed, as are future plans for further deploying metacomputing technologies in the context of materials science and mechanical engineering.
Single-cell herpes simplex virus type 1 infection of neurons using drop-based microfluidics reveals heterogeneous replication kinetics
Authors: Fredrikson Jacob P. , Domanico Luke F. , Pratt Shawna L. , Loveday Emma K. , Taylor Matthew P. , Chang Connie B.
Published: February 2024

Single-cell analyses of viral infections reveal heterogeneity that is not detected by traditional population-level studies. This study applies drop-based microfluidics to investigate the dynamics of herpes simplex virus type 1 (HSV-1) infection of neurons at the single-cell level. We used micrometer-scale Matrigel beads, termed microgels, to culture individual murine superior cervical ganglia (SCG) neurons or epithelial cells. Microgel-cultured cells are encapsulated in individual media-in-oil droplets with a dual–fluorescent reporter HSV-1, enabling real-time observation of viral gene expression and replication. Infection within drops revealed that the kinetics of initial viral gene expression and replication were dependent on the inoculating dose. Notably, increasing inoculating doses led to earlier onset of viral gene expression and more frequent productive viral replication. These observations provide crucial insights into the complexity of HSV-1 infection in neurons and emphasize the importance of studying single-cell outcomes of viral infection. These techniques for cell culture and infection in drops provide a foundation for future virology and neurobiology investigations.
Epistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors
Authors: Hikichi Yuta , Grover Jonathan R. , Schäfer Alicia , Mothes Walther , Freed Eric O.
Published: March 2024

People living with human immunodeficiency virus (HIV) receiving integrase strand transfer inhibitors (INSTIs) have been reported to experience virological failure in the absence of resistance mutations in integrase. To elucidate INSTI resistance mechanisms, we propagated HIV-1 in the presence of escalating concentrations of the INSTI dolutegravir. HIV-1 became resistant to dolutegravir by sequentially acquiring mutations in the envelope glycoprotein (Env) and the nucleocapsid protein. The selected Env mutations enhance the ability of the virus to spread via cell-cell transfer, thereby increasing the multiplicity of infection (MOI). While the selected Env mutations confer broad resistance to multiple classes of antiretrovirals, the fold resistance is ~2 logs higher for INSTIs than for other classes of drugs. We demonstrate that INSTIs are more readily overwhelmed by high MOI than other classes of antiretrovirals. Our findings advance the understanding of how HIV-1 can evolve resistance to antiretrovirals, including the potent INSTIs, in the absence of drug-target gene mutations.
Deep-sea
in situ
and laboratory multi-omics provide insights into the sulfur assimilation of a deep-sea
Chloroflexota
bacterium
Authors: Zheng Rikuan , Wang Chong , Sun Chaomin
Published: February 2024

Chloroflexota
bacteria are abundant and globally distributed in various deep-sea ecosystems. It has been reported based on metagenomics data that two deep-sea
Chloroflexota
lineages (the SAR202 group and
Dehalococcoidia
class) have the potential to drive sulfur cycling. However, the absence of cultured
Chloroflexota
representatives is a significant bottleneck toward understanding their contribution to the deep-sea sulfur cycling. In this study, we find that
Phototrophicus methaneseepsis
ZRK33 isolated from deep-sea sediment has a heterotrophic lifestyle and can assimilate sulfate and thiosulfate. Using combined physiological, genomic, proteomic, and
in situ
transcriptomic methods, we find that strain ZRK33 can perform assimilatory sulfate reduction in both laboratory and deep-sea conditions. Metabolism of sulfate or thiosulfate by strain ZRK33 significantly promotes the transport and degradation of various macromolecules and thereby stimulates the energy production. In addition, metagenomic results show that genes associated with assimilatory and dissimilatory sulfate reduction are ubiquitously distributed in the metagenome-assembled genomes of
Chloroflexota
members derived from deep-sea sediments. Metatranscriptomic results also show that the expression levels of related genes are upregulated, strongly suggesting that
Chloroflexota
bacteria may play undocumented roles in deep-sea sulfur cycling.

IMPORTANCE

The cycling of sulfur is one of Earth's major biogeochemical processes and is closely related to the energy metabolism of microorganisms living in the deep-sea cold seep and hydrothermal vents. To date, some of the members of
Chloroflexota
are proposed to play a previously unrecognized role in sulfur cycling. However, the sulfur metabolic characteristics of deep-sea
Chloroflexota
bacteria have never been reported, and remain to be verified in cultured deep-sea representatives. Here, we show that the deep-sea
Chloroflexota
bacterium ZRK33 can perform sulfate assimilation in both laboratory and deep-sea conditions, which expands our knowledge of the sulfur metabolic potential of deep-sea
Chloroflexota
bacteria. We also show that the genes associated with assimilatory and dissimilatory sulfate reduction ubiquitously distribute in the deep-sea
Chloroflexota
members, providing hints to the roles of
Chloroflexota
bacteria in deep-sea sulfur biogeochemical cycling.
Pathogenomic analysis and characterization of
Pasteurella multocida
strains recovered from human infections
Authors: Smallman Thomas R. , Perlaza-Jiménez Laura , Wang Xiaochu , Korman Tony M. , Kotsanas Despina , Gibson Justine S. , Turni Conny , Harper Marina , Boyce John D.
Published: March 2024

Pasteurella multocida
is an upper respiratory tract commensal in several mammal and bird species but can also cause severe disease in humans and in production animals such as poultry, cattle, and pigs. In this study, we performed whole-genome sequencing of
P. multocida
isolates recovered from a range of human infections, from the mouths of cats, and from wounds on dogs. Together with publicly available
P. multocida
genome sequences, we performed phylogenetic and comparative genomic analyses. While isolates from cats and dogs were spread across the phylogenetic tree, human infections were caused almost exclusively by subsp.
septica
strains. Most of the human isolates were capsule type A and LPS type L1 and L3; however, some strains lacked a capsule biosynthesis locus, and some strains contained a novel LPS outer-core locus, distinct from the eight LPS loci that can currently be identified using an LPS multiplex PCR. In addition, the
P. multocida
strains isolated from human infections contained novel mobile genetic elements. We compiled a curated database of known
P. multocida
virulence factor and antibiotic resistance genes (PastyVRDB) allowing for detailed characterization of isolates. The majority of human
P. multocida
isolates encoded a reduced range of iron receptors and contained only one filamentous hemagglutinin gene. Finally, gene-trait analysis identified a putative L-fucose uptake and utilization pathway that was over-represented in subsp.
septica
strains and may represent a novel host predilection mechanism in this subspecies. Together, these analyses have identified pathogenic mechanisms likely important for
P. multocida
zoonotic infections.

IMPORTANCE

Pasteurella multocida
can cause serious infections in humans, including skin and wound infections, pneumonia, peritonitis, meningitis, and bacteraemia. Cats and dogs are known vectors of human pasteurellosis, transmitting
P. multocida
via bite wounds or contact with animal saliva. The mechanisms that underpin
P. multocida
human predilection and pathogenesis are poorly understood. With increasing identification of antibiotic-resistant
P. multocida
strains, understanding these mechanisms is vital for developing novel treatments and control strategies to combat
P. multocida
human infection. Here, we show that a narrow range of
P. multocida
strains cause disease in humans, while cats and dogs, common vectors for zoonotic infections, can harbor a wide range of
P. multocida
strains. We also present a curated
P. multocida
-specific database, allowing quick and detailed characterization of newly sequenced
P. multocida
isolates.
Impact of rift history on the structural style of intracontinental rift-inversion orogens
Authors: Vasey Dylan A. , Naliboff John B. , Cowgill Eric , Brune Sascha , Glerum Anne , Zwaan Frank
Published: March 2024

Although many collisional orogens form after subduction of oceanic lithosphere between two continents, some orogens result from strain localization within a continent via inversion of structures inherited from continental rifting. Intracontinental rift-inversion orogens exhibit a range of structural styles, but the underlying causes of such variability have not been extensively explored. We use numerical models of intracontinental rift inversion to investigate the impact of parameters including rift structure, rift duration, post-rift cooling, and convergence velocity on orogen structure. Our models reproduce the natural variability of rift-inversion orogens and can be categorized using three endmember styles: asymmetric underthrusting (AU), distributed thickening (DT), and localized polarity flip (PF). Inversion of narrow rifts tends to produce orogens with more localized deformation (styles AU and PF) than those resulting from wide rifts. However, multiple combinations of the parameters we investigated can produce the same structural style. Thus, our models indicate no unique relationship between orogenic structure and the conditions prior to and during inversion. Because the style of rift-inversion orogenesis is highly contingent upon the rift history prior to inversion, knowing the geologic history that preceded rift inversion is essential for translating orogenic structure into the processes that produced that structure.
Lithospheric mantle as a metal storage reservoir for orogenic gold deposits in active continental margins: Evidence from Hg isotopes
Authors: Zhang Jing-Yuan , Qiu Kun-Feng , Yin Runsheng , Long Zheng-Yu , Feng Yue-Chuan , Yu Hao-Cheng , Gao Zi-Yue , Deng Jun
Published: March 2024

The subcontinental lithospheric mantle (SCLM) is now suggested by many workers to play a role in the formation of orogenic gold deposits in active continental margins, given that the gold and volatiles may be introduced into the SCLM during plate subduction. The giant Cretaceous Jiaodong gold province within the North China block occurs in a convergent margin setting where there is no terrane accretion, thus eliminating from consideration the commonly accepted metal and fluid source reservoir for orogenic gold—the metamorphosed upper crust of an active orogenic belt. Thus, the auriferous fluids were released below the high-grade Archean cratonic rocks from either enriched SCLM or directly from the subducted oceanic slab. Mercury (Hg) isotopes allow fingerprinting of isotopically distinct reservoirs, discriminating between the two possibilities. We present Hg isotope data for a set of pyrite grains, native gold, and lamprophyres from six main gold districts in the Jiaodong gold province. These samples dominantly yielded near-zero Δ199Hg (0‰ ± 0.1‰), within uncertainty of the mantle Δ199Hg value. The results provide novel evidence that the SCLM predominantly controlled the Hg budget of the Jiaodong gold deposits, implying that the SCLM acted as a buffer for the crustal mass-independent fractionation Hg signatures and a storage reservoir for gold and volatiles. Consequently, during slab subduction, gold and volatiles were recycled and stored within the SCLM and were later released from the mantle during uplift and relaxation of compressional tectonics.
Supplemental Material: An ongoing lithospheric dripping process beneath northeast China and its impact on intraplate volcanism
Authors: Lin Feiyu , Zhang Nan , Guo Zhen , al. et
Published: February 2024

Methodology, Figures S1–S4, and Tables S1 and S2.  
Spatiotemporal Variability of the Characteristics of the Black Sea Eddies Based on the Results of Their Three-Dimensional Identification Using NEMO Model Simulation
Authors: Kubryakov A. A. , Mizyuk A. I.
Published: March 2024

The vertical variability of the geometric, dynamic, and thermohaline characteristics of Black Sea eddies is studied using three-dimensional identification of closed streamlines based on the results of simulations of the NEMO model in 2006–2016. The vertical extent of eddies depends linearly on their orbital velocity and significantly affects the speed of their translation motion. The influence of the background current on the upper part of the eddy leads to the mean tilt of the vertical axis of anticyclones in the cyclonic direction and this tilt is maximum in the zone of the Black Sea Rim Current. The eddies occupying the upper layer (up to 150 m) move relatively quickly at a speed of 0.08–0.14 m/s, since they are advected by the Rim Current. The most intense eddy dynamics is observed over the continental slope in the upper 20–70 m layer, where the probability of observing eddies exceeds 30%. Several maxima appear in the surface layer on the shallow northwestern shelf near the mouths of the Danube, Southern Bug, and Dnieper rivers. The relationship between the orbital velocity of eddies, their thermohaline structure, and stratification were estimated. Stability decreases in anticyclonic eddies within the layer 40–100 m due to the lowering of the pycnocline, and in cyclones it increases due to its elevation; in the underlying layers a compensating change of the opposite sign is observed. However, as the orbital velocity increases in the eddies of both signs, a decrease in stratification occurs in the upper 0–100 m layer, which is probably associated with an increase in the vertical shear of the current velocity. Three-dimensional identification of eddies makes it possible to track in detail changes in the individual characteristics of an eddy during its evolution. Using the example of an eddy off the Anatolian coast, it is shown that intensification of anticyclones is associated with the processes of entrainment of shelf waters, which can be one of the important sources of potential energy for anticyclones in the Black Sea.
Survival following lung volume reduction procedures: results from the UK Lung Volume Reduction (UKLVR) registry
Authors: Buttery S C , Lewis A , Alzetani A , Bolton C E , Curtis K J , Dodd J W , Habib A M , Hussain A , Havelock T , Jordan S , Kallis C , Kemp S V , Kirk A , Lawson R A , Mahadeva R , Munavvar M , Naidu B , Rathinam S , Shackcloth M , Shah P L , Tenconi S , Hopkinson N S
Published: March 2024

Introduction

Lung volume reduction surgery (LVRS) and endobronchial valve (EBV) placement can produce substantial benefits in appropriately selected people with emphysema. The UK Lung Volume Reduction (UKLVR) registry is a national multicentre observational study set up to support quality standards and assess outcomes from LVR procedures at specialist centres across the UK.

Methods

Data were analysed for all patients undergoing an LVR procedure (LVRS/EBV) who were recruited into the study at participating centres between January 2017 and June 2022, including; disease severity and risk assessment, compliance with guidelines for selection, procedural complications and survival to February 2023.

Results

Data on 541 patients from 14 participating centres were analysed. Baseline disease severity was similar in patients who had surgery n=244 (44.9%), or EBV placement n=219 (40.9%), for example, forced expiratory volume in 1 s (FEV1)32.1 (12.1)% vs 31.2 (11.6)%. 89% of cases had discussion at a multidisciplinary meeting recorded. Median (IQR) length of stay postprocedure for LVRS and EBVs was 12 (13) vs 4 (4) days(p=0.01). Increasing age, male gender and lower FEV1%predicted were associated with mortality risk, but survival did not differ between the two procedures, with 50 (10.8%) deaths during follow-up in the LVRS group vs 45 (9.7%) following EBVs (adjusted HR 1.10 (95% CI 0.72 to 1.67) p=0.661)

Conclusion

Based on data entered in the UKLVR registry, LVRS and EBV procedures for emphysema are being performed in people with similar disease severity and long-term survival is similar in both groups.
Exercise rehabilitation programmes for pulmonary hypertension: a systematic review of intervention components and reporting quality
Authors: McGregor Gordon , Powell Richard , Finnegan Susanne , Nichols Simon , Underwood Martin
Published: March 2024

Objectives

To identify the components, and assess the reporting quality, of exercise training interventions for people living with pulmonary hypertension.

Design

Systematic review with analysis of intervention reporting quality using the Consensus on Exercise Reporting Template (CERT).

Data sources

Eligible studies in the Cochrane Systematic Review of exercise-based rehabilitation for pulmonary hypertension, updated with a new search of relevant databases from 1 August 2016 to 15 January 2018.

Eligibility criteria

Peer-reviewed journal articles of randomised and non-randomised controlled trials, and non-controlled prospective observational studies, investigating dynamic exercise training interventions in adult humans with diagnosed pulmonary hypertension, reporting on at least one physiological and/or psychosocial outcome.

Results

Interventions typically involved cycle ergometry and walking. They were delivered as 3-week inpatient, or outpatient and/or home-based programmes, lasting for 4–15 weeks. Components relating specifically to exercise prescription were described satisfactorily and in more detail than motivational/behavioural change strategies, adherence and fidelity. Mean CERT score was 13.1 (range 8–17) out of a possible maximum score of 19. No studies fully reported every aspect of an exercise intervention to the standard recommended by CERT.

Summary/conclusion

Considerable variability was evident in the components and reporting quality of interventions for exercise rehabilitation studies in pulmonary hypertension. Interventional studies using exercise training should pay greater attention to describing motivational/behavioural change strategies, adherence and fidelity. Detailed description of these parameters is essential for the safe and effective replication of exercise rehabilitation interventions for pulmonary hypertension in clinical practice.

Trial registration number

NCT42018085558.
Concussion in adolescent rugby union players: comprehensive acute assessment protocol and development of the SSC concussion passport to monitor long-term health
Authors: Cosgrave Ciaran , Fuller Colm , Franklyn-Miller Andy , Falvey Eanna , Beirne Cliff , Ryan John , McCrory Paul
Published: March 2024

Introduction

Sports-related concussion (SRC) can be challenging to diagnose, assess and manage. Much of the SRC research is conducted on adults. The assessment of SRC should aim to identify deficits using a detailed multimodal assessment; however, most studies investigating the effects of SRC use diagnostic tools in isolation. It is likely that a combination of diagnostic tests will improve diagnostic accuracy. In this study, we aim to investigate how concussion affects adolescent rugby players and how a variety of diagnostic tools interact with each other as participants recover from their injury. The study will also determine the logistics of recording an individual’s concussion history on a virtual ‘Concussion Passport’ that would remain with the individual throughout their sporting career to allow monitoring of long-term health.

Methods and analysis

All rugby players (n=211) from the Senior Cup Teams of five schools in Dublin, Ireland will be invited to participate in the study. Baseline testing will be performed at the Sports Surgery Clinic, Dublin (SSC) before the rugby season commences. Participants will be followed up over the course of the rugby season. At baseline and at each postconcussion visit, participants will complete the following: Questionnaire, Sports Concussion Assessment Tool 3, Balance Error Scoring System, Computerised Neurocognitive Testing, Vestibulo-ocular assessment, King Devick test, Graded exercise test, Blood tests, Neck strength, FitBit.

Ethics and dissemination

Ethical approval was obtained from the Sports Surgery Clinic Research Ethics Committee (Approval number: SSC 0020). On completion of the study, further papers will be written and published to present the results of the various tests.

Trial registration number

NCT03624634.
Pandemic phase-related racial and ethnic disparities in COVID-19 positivity and outcomes among patients presenting to emergency departments during the first two pandemic waves in the USA
Authors: Khosla Shaveta , Del Rios Marina , Chisolm-Straker Makini , Bilal Saadiyah , Jang Timothy B , Wang Hao , Hartley Molly , Loo George T , d'Etienne James P , Newgard Craig D , Courtney D Mark , Choo Esther K , Lin Michelle P , Kline Jeffrey A
Published: March 2024

Background

In many countries including the USA, the UK and Canada, the impact of COVID-19 on people of colour has been disproportionately high but examination of disparities in patients presenting to ED has been limited. We assessed racial and ethnic differences in COVID-19 positivity and outcomes in patients presenting to EDs in the USA, and the effect of the phase of the pandemic on these outcomes.

Methods

This is a retrospective cohort study of adult patients tested for COVID-19 during, or 14 days prior to, the index ED visit in 2020. Data were obtained from the National Registry of Suspected COVID-19 in Emergency Care network which has data from 155 EDs across 27 US states. Hierarchical models were used to account for clustering by hospital. The outcomes included COVID-19 diagnosis, hospitalisation at index visit, subsequent hospitalisation within 30 days and 30-day mortality. We further stratified the analysis by time period (early phase: March–June 2020; late phase: July–September 2020).

Results

Of the 26 111 adult patients, 38% were non-Hispanic White (NHW), 29% Black, 20% Hispanic/Latino, 3% Asian and 10% all others; half were female. The median age was 56 years (IQR 40–69), and 53% were diagnosed with COVID-19; of those, 59% were hospitalised at index visit. Of those discharged from ED, 47% had a subsequent hospitalisation in 30 days. Hispanic/Latino patients had twice (adjusted OR (aOR) 2.3; 95% CI 1.8 to 3.0) the odds of COVID-19 diagnosis than NHW patients, after adjusting for age, sex and comorbidities. Black, Asian and other minority groups also had higher odds of being diagnosed (compared with NHW patients). On stratification, this association was observed in both phases for Hispanic/Latino patients. Hispanic/Latino patients had lower odds of hospitalisation at index visit, but when stratified, this effect was only observed in early phase. Subsequent hospitalisation was more likely in Asian patients (aOR 3.1; 95% CI 1.1 to 8.7) in comparison with NHW patients. Subsequent ED visit was more likely in Blacks and Hispanic/Latino patients in late phase.

Conclusion

We found significant differences in ED outcomes that are not explained by comorbidity burden. The gap decreased but persisted during the later phase in 2020.
Unmet research needs in sustainable luminal gastroenterology practice
Authors: Dhar Anjan , Haboubi Hasan , Selinger Christian , Arasaradnam Ramesh
Published: March 2024

While it is now well recognised that gastroenterology, hepatology and endoscopy are major contributors to climate change on account of the amount of greenhouse gases (GHGs) that are generated in these specialties, systematic research that measures the exact amount of GHGs generated by different aspects of clinical care in the specialty is lacking. Similarly, while there are a number of publications highlighting the potential strategies for the reduction of GHGs, interventional studies assessing the impact of change are only beginning to be carried out. As such, there are a number of unmet research needs in this field and this mini review is aimed at discussing some of these.
Novel and unusualUSP6fusion partners in aneurysmal bone cyst and their role in pathogenesis and histopathological evaluation of this disease
Authors: Balko Jan , Golas William , Kaspar Ludvik , Krskova Lenka , Strnadova Martina , Kotis Johana , Zamecnik Josef
Published: March 2024

Aims

The purpose of this study is to report novel and unusualUSP6fusion partners in aneurysmal bone cysts (ABCs). These findings may be useful in routine diagnostics as well as in studying the biology ofUSP6-related disorders.

Methods

A cohort of seven patients diagnosed with ABC examined between 2014 and 2023 at Motol University Hospital in Prague was included into this retrospective non-randomised study. All cases were analysed using histopathological evaluation, immunohistochemistry and Anchored multiplex RNA methods. Demographic characteristics and clinical data were also analysed.

Results

We identified two novel (ZFXandIP6K2), three unusual (MEF2A, EIF1andCOL1A2) and two common (CDH11) fusion partners withUSP6gene among all seven cases of ABC.

Conclusions

Cases in our study were diagnosed as ABCs due to characteristic clinical and morphological presentation. However, not all cases are as self-evident, and molecular testing is necessary. The identification of these gene alterations can be useful in distinction between true ABC and ABC-like changes among many benign and malignant bone tumours.
Keeping it in the family: reproduction beyond genetic parenthood
Authors: Cutas Daniela , Smajdor Anna
Published: March 2024

Recent decades have seen the facilitation of unconventional or even extraordinary reproductive endeavours. Sperm has been harvested from dying or deceased men at the request of their wives; reproductive tissue has been surgically removed from children at the request of their parents; deceased adults’ frozen embryos have been claimed by their parents, in order to create grandchildren; wombs have been transplanted from mothers to their daughters. What is needed for requests to be honoured by healthcare staff is that they align with widely shared expectations about what people’s reproductive potential ought to be, what marital relationships ought to result in, and which kinds of ties are desirable between parents and children. Costly and invasive technologies are not considered excessive when they are used to support the building of appropriate families. However, deviations from dominant reproductive norms, even if technologically simple and convenient to the participants, are unlikely to receive support. In this paper, we offer examples of such deviations and explore their implications. If reproduction is important as a way of creating genetic relationships, should reproductive material in storage be offered to genetic relatives other than the people from whom it originated? And if parents are allowed to have reproductive material collected from their offspring, or even to use it to create babies, should offspring likewise be allowed to use their parents’ reproductive material? We tackle these questions and suggest ways in which interests in genetic ties could be operationalised in a more coherent and less-invasive manner than they currently are.
Does sex influence the natural history of idiopathic adult-onset dystonia?
Authors: Velucci Vittorio , Idrissi Sarah , Pellicciari Roberta , Esposito Marcello , Trinchillo Assunta , Belvisi Daniele , Fabbrini Giovanni , Ferrazzano Gina , Terranova Carmen , Girlanda Paolo , Majorana Giovanni , Rizzo Vincenzo , Bono Francesco , Idone Giovanni , Laterza Vincenzo , Avanzino Laura , Di Biasio Francesca , Marchese Roberta , Castagna Anna , Ramella Marina , Lettieri Christian , Rinaldo Sara , Altavista Maria Concetta , Polidori Luigi , Bertolasi Laura , Tozzi Maria Chiara , Erro Roberto , Barone Paolo , Barbero Pierangelo , Ceravolo Roberto , Mascia Marcello Mario , Ercoli Tommaso , Muroni Antonella , Artusi Carlo Alberto , Zibetti Maurizio , Scaglione Cesa Lorella Maria , Bentivoglio Anna Rita , Cotelli Maria Sofia , Magistrelli Luca , Cossu Giovanni , Albanese Alberto , Squintani Giovanna Maddalena , Schirinzi Tommaso , Gigante Angelo Fabio , Maderna Luca , Eleopra Roberto , Pisani Antonio , Cassano Daniela , Romano Marcello , Rizzo Marina , Berardelli Alfredo , Defazio Giovanni
Published: March 2024

Background

Several earlier studies showed a female predominance in idiopathic adult-onset dystonia (IAOD) affecting the craniocervical area and a male preponderance in limb dystonia. However, sex-related differences may result from bias inherent to study design. Moreover, information is lacking on whether sex-related differences exist in expressing other dystonia-associated features and dystonia spread.

Objective

To provide accurate information on the relationship between sex differences, motor phenomenology, dystonia-associated features and the natural history of IAOD.

Methods

Data of 1701 patients with IAOD from the Italian Dystonia Registry were analysed.

Results

Women predominated over men in blepharospasm, oromandibular, laryngeal and cervical dystonia; the sex ratio was reversed in task-specific upper limb dystonia; and no clear sex difference emerged in non-task-specific upper limb dystonia and lower limb dystonia. This pattern was present at disease onset and the last examination. Women and men did not significantly differ for several dystonia-associated features and tendency to spread. In women and men, the absolute number of individuals who developed dystonia tended to increase from 20 to 60 years and then declined. However, when we stratified by site of dystonia onset, different patterns of female-to-male ratio over time could be observed in the various forms of dystonia.

Conclusions

Our findings provide novel evidence on sex as a key mediator of IAOD phenotype at disease onset. Age-related sexual dimorphism may result from the varying exposures to specific age-related and sex-related environmental risk factors interacting in a complex manner with biological factors such as hormonal sex factors.
Major bleeding in patients with atrial fibrillation treated with apixaban versus warfarin in combination with amiodarone: nationwide cohort study
Authors: Fritz Hansson Astrid , Modica Angelo , Renlund Henrik , Christersson Christina , Held Claes , Batra Gorav
Published: March 2024

Background

Amiodarone is an established treatment for atrial fibrillation (AF) but might interfere with the metabolism of apixaban or warfarin. Therefore, the aim was to investigate the occurrence of major bleeding among patients with AF treated with amiodarone in combination with apixaban or warfarin.

Methods

Retrospective observational study using Swedish health registers. All patients with AF in the National Patient Register and the National Dispensed Drug Register with concomitant use of amiodarone and warfarin or apixaban between 1 June 2013 and 31 December 2018 were included. Propensity score matching was performed, and matched cohorts were compared using Cox proportional HRs. The primary outcome was major bleeding resulting in hospitalisation based on International Classification of Diseases (ICD)-10 codes. Secondary outcomes included intracranial bleeding, gastrointestinal bleeding and other bleeding. Exploratory outcomes included ischaemic stroke/systemic embolism and all-cause/cardiovascular (CV) mortality.

Results

A total of 12 103 patients met the inclusion criteria and 8686 patients were included after propensity score matching. Rates of major bleeding were similar in the apixaban (4.3/100 patient-years) and warfarin cohort (4.5/100 patient-years) (HR: 1.03; 95% CI: 0.76 to 1.39) during median follow-up of 4.4 months. Similar findings were observed for secondary outcomes including gastrointestinal bleeding and other bleeding, and exploratory outcomes including ischaemic stroke/systemic embolism and all-cause/CV mortality.

Conclusions

Among patients treated with amiodarone in combination with apixaban or warfarin, major bleeding and thromboembolic events were rare and with no significant difference between the treatment groups.

EUPAS registry number

EUPAS43681.
Meta-analyses of the global multilocus genotypes of the human pathogen Campylobacter jejuni
Authors: Poorrashidi Monir , Hitchcock Megan , Xu Jianping
Published: March 2024

Campylobacter infections are a leading cause of bacterial diarrheal illness worldwide, with increasing reports of outbreaks in both developing and developed countries. Most studies investigating strain genotypes and epidemiology of Campylobacter jejuni examined on a local scale. Using the archived multilocus sequence typing data at seven loci, and associated strain metadata from the PubMLST database, here we investigated the spatial and temporal genetic structure of the global population of C. jejuni. Our analyses revealed evidence for clonal dispersals of multiple sequence types (STs) among countries and continents. However, despite the observed clonal dispersal and that most genetic variations were found within individual geographic subpopulations, both the non-clone-corrected and clone-corrected samples showed evidence of significant genetic differentiation among national and continental subpopulations, with non-clone-corrected samples showing greater differentiation than clone-corrected samples. Phylogenetic incompatibility analyses provided evidence for recombination within each continental subpopulation. However, linkage disequilibrium analyses rejected the hypothesis of random recombination across the samples. Temporally, multiple STs were found to persist across four decades and the five globally most common STs showed relatively stable frequencies over the last two decades. We discussed the implications of our results to food security, disease transmission, and public health management.
The development of computational methods for Feynman diagrams
Authors: Harlander Robert V. , Martinez Jean-Philippe
Published: March 2024

Over the last 70 years, Feynman diagrams have played an essential role in the development of many theoretical predictions derived from the standard model Lagrangian. In fact, today they have become an essential and seemingly irreplaceable tool in quantum field theory calculations. In this article, we propose to explore the development of computational methods for Feynman diagrams with a special focus on their automation, drawing insights from both theoretical physics and the history of science. From the latter perspective, the article particularly investigates the emergence of computer algebraic programs, such as the pioneering , , and , designed to handle the intricate calculations associated with Feynman diagrams. This sheds light on the many challenges faced by physicists when working at higher orders in perturbation theory and reveal, as exemplified by the test of the validity of quantum electrodynamics at the turn of the 1960s and 1970s, the indispensable necessity of computer-assisted procedures. In the second part of the article, a comprehensive overview of the current state of the algorithmic evaluation of Feynman diagrams is presented from a theoretical point of view. It emphasizes the key algorithmic concepts employed in modern perturbative quantum field theory computations and discusses the achievements, ongoing challenges, and potential limitations encountered in the application of the Feynman diagrammatic method. Accordingly, we attribute the enduring significance of Feynman diagrams in contemporary physics to two main factors: the highly algorithmic framework developed by physicists to tackle these diagrams and the successful advancement of algebraic programs used to process the involved calculations associated with them.
Learning variational models with unrolling and bilevel optimization
Authors: Brauer Christoph , Breustedt Niklas , de Wolff Timo , Lorenz Dirk A.
Published: March 2024

In this paper, we consider the problem of learning variational models in the context of supervised learning via risk minimization. Our goal is to provide a deeper understanding of the two approaches of learning of variational models via bilevel optimization and via algorithm unrolling. The former considers the variational model as a lower level optimization problem below the risk minimization problem, while the latter replaces the lower level optimization problem by an algorithm that solves said problem approximately. Both approaches are used in practice, but unrolling is much simpler from a computational point of view. To analyze and compare the two approaches, we consider a simple toy model, and compute all risks and the respective estimators explicitly. We show that unrolling can be better than the bilevel optimization approach, but also that the performance of unrolling can depend significantly on further parameters, sometimes in unexpected ways: While the stepsize of the unrolled algorithm matters a lot (and learning the stepsize gives a significant improvement), the number of unrolled iterations plays a minor role.
DTSSN: A Distributed Trustworthy Sensor Service Network Architecture for Smart City
Authors: Pang Shengye , Luo Jiayin , Zhao Xinkui , Chen Jintao , Wang Fan , Yin Jianwei
Published: February 2024

The smart city is an increasingly popular concept when it comes to urban development. In a smart city, numerous sensor services are generated by IoT sensors in a distributed manner, requiring proper management and effective interaction to guarantee the connectivity of different regions. However, the sensitive nature of sensor data raises concerns over joining public cloud centers or edge servers, despite assurances of their reliability from providers. Local deployment and maintenance of sensor services may cause these service providers to become ”data isolated islands”, hindering the construction process of smart city. This paper proposes a distributed trustworthy sensor service network architecture named DTSSN to support the building of a fully distributed sensor service network. The proposed network architecture operates through the collaboration of two core devices, the sensor service switch and router, to effectively enable the registration, discovery, invocation, transaction, and monitoring of cross-region sensor services. Then, a lightweight trustworthy transaction mechanism based on blockchain is proposed to realize SLA-based automatic service transaction while reducing potential risks in the service network. Comparative analysis and simulation experiments validate the effectiveness of the DTSSN architecture in terms of scalability, availability, and trustworthiness, underscoring its potential in advancing smart city development and governance.
FortiFix
: A Fault Attack Aware Compiler Framework for Crypto Implementations
Authors: K Keerthi , Rebeiro Chester
Published: March 2024

Fault attacks are one of the most powerful forms of cryptanalytic attack on embedded systems, which can corrupt a cipher’s operations leading to a breach of confidentiality and integrity. A single precisely injected fault during the execution of a cipher can be exploited to retrieve the secret key in a few milliseconds. Naive countermeasures introduced into implementation can lead to huge overheads, making them unusable in resource-constraint environments. However, optimized countermeasures require significant knowledge, not only about the attack but also on the the cryptographic properties of the cipher, the program structure, and the underlying hardware architecture. This makes the protection against fault attacks tedious and error prone.

In this article, we introduce
FortiFix
, the first automated compiler framework that can detect and patch fault exploitable regions in a block cipher implementation. The framework has two phases. The
pre-compilation phase
identifies regions in the source code of a block cipher that are vulnerable to fault attacks. The second phase is incorporated as transformation passes in the LLVM compiler to find exploitable instructions, quantify the impact of a fault on these instructions, and finally insert appropriate countermeasures based on user-defined security requirements. As a proof of concept, we have evaluated two block cipher implementations, AES-128 and CLEFIA-128, on three different hardware platforms: MSP430 (16-bit), ARM (32-bit), and RISCV (32-bit).
Recent Developments in Aerosol Pulmonary Drug Delivery: New Technologies, New Cargos, and New Targets
Authors: Woodward Ian R. , Fromen Catherine A.
Published: March 2024

There is nothing like a global pandemic to motivate the need for improved respiratory treatments and mucosal vaccines. Stimulated by the COVID-19 pandemic, pulmonary aerosol drug delivery has seen a flourish of activity, building on the prior decades of innovation in particle engineering, inhaler device technologies, and clinical understanding. As such, the field has expanded into new directions and is working toward the efficient delivery of increasingly complex cargos to address a wider range of respiratory diseases. This review seeks to highlight recent innovations in approaches to personalize inhalation drug delivery, deliver complex cargos, and diversify the targets treated and prevented through pulmonary drug delivery. We aim to inform readers of the emerging efforts within the field and predict where future breakthroughs are expected to impact the treatment of respiratory diseases.
Three-Dimensional Morphology of Polymeric Membranes from Electron Tomography
Authors: Ghasemi Masoud , Geitner Michael , O'Connell Agatha , Gomez Enrique D.
Published: March 2024

Recent advances in the water–energy landscape hinge upon our improved understanding of the complex morphology of materials involved in water treatment and energy production. Due to their versatility and tunability for applications ranging from drug delivery to fuel cells, polymeric systems will play a crucial role in shaping the future of water–energy nexus applications. Electron tomography (ET) stands as a transformative approach for elucidating the intricate structures inherent to polymers, offering unparalleled insights into their nanoscale architectures and functional properties in three dimensions. In particular, the various morphological and chemical characteristics of polymer membranes provide opportunities for perturbations to standard ET for the study of these systems. We discuss the applications of transmission electron microscopy in establishing structure–function relationships in polymeric membranes with an emphasis on traditional ET and cryogenic ET (cryo-ET). The synergy between ET and cryo-ET to unravel structural complexities and dynamic behaviors of polymer membranes holds immense potential in driving progress and innovation across frontiers related to water–energy nexus applications.
The Myriad Decision at 10
Authors: Sherkow Jacob S. , Cook-Deegan Robert , Greely Henry T.
Published: March 2024

A decade ago, the US Supreme Court decided Association for Molecular Pathology v. Myriad Genetics, Inc., concluding that isolated genes were not patentable subject matter. Beyond being a mere patent dispute, the case was a political and cultural phenomenon, viewed as a harbinger for the health of the biotechnology industry. With a decade of perspective, though, Myriad's impact seems much narrower. The law surrounding patentable subject matter—while greatly transformed—only centered on Myriad in small part. The case had only a modest impact on patenting practices both in and outside the United States. And persistent efforts to legislatively overturn the decision have not borne fruit. The significance of Myriad thus remains, even a decade later, hidden by larger developments in science and law that have occurred since the case was decided.