bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Machine Learning and Lay Care Coaches to Increase Advance Care Planning Conversations for Patients With Metastatic Cancer
Authors: Gensheimer Michael F. , Gupta Divya , Patel Manali I. , Fardeen Touran , Hildebrand Rachel , Teuteberg Winifred , Seevaratnam Briththa , Asuncion Mary Khay , Alves Nina , Rogers Brian , Hansen Jennifer , DeNofrio Jan , Shah Nigam H. , Parikh Divya , Neal Joel , Fan Alice C. , Moore Kaidi , Ruiz Shann , Li Connie , Khaki Ali Raza , Pagtama Judy , Chien Joanne , Brown Tiffany , Tisch Alison Holmes , Das Millie , Srinivas Sandhya , Roy Mohana , Wakelee Heather , Myall Nathaniel J. , Huang Jane , Shah Sumit , Lee Howard , Ramchandran Kavitha
Published: November 2022

PURPOSE:

Patients with metastatic cancer benefit from advance care planning (ACP) conversations. We aimed to improve ACP using a computer model to select high-risk patients, with shorter predicted survival, for conversations with providers and lay care coaches. Outcomes included ACP documentation frequency and end-of-life quality measures.

METHODS:

In this study of a quality improvement initiative, providers in four medical oncology clinics received Serious Illness Care Program training. Two clinics (thoracic/genitourinary) participated in an intervention, and two (cutaneous/sarcoma) served as controls. ACP conversations were documented in a centralized form in the electronic medical record. In the intervention, providers and care coaches received weekly e-mails highlighting upcoming clinic patients with < 2 year computer-predicted survival and no prior prognosis documentation. Care coaches contacted these patients for an ACP conversation (excluding prognosis). Providers were asked to discuss and document prognosis.

RESULTS:

In the four clinics, 4,968 clinic visits by 1,251 patients met inclusion criteria (metastatic cancer with no prognosis previously documented). In their first visit, 28% of patients were high-risk (< 2 year predicted survival). Preintervention, 3% of both intervention and control clinic patients had ACP documentation during a visit. By intervention end (February 2021), 35% of intervention clinic patients had ACP documentation compared with 3% of control clinic patients. Providers' prognosis documentation rate also increased in intervention clinics after the intervention (2%-27% in intervention clinics, P < .0001; 0%-1% in control clinics). End-of-life care intensity was similar in intervention versus control clinics, but patients with ≥ 1 provider ACP edit met fewer high-intensity care measures ( P = .04).

CONCLUSION:

Combining a computer prognosis model with care coaches increased ACP documentation.
How do reputation and conformity promote cooperation in the prisoner's dilemma?
Authors: Liu C. , Wang H. , Dai Y.
Published: November 2022

In evolutionary games, many mechanisms have been proposed to promote cooperation between individuals and the heterogeneity of these mechanisms has been widely investigated. However, the joint effects and heterogeneity of multiple mechanisms have not been adequately studied. Here, we introduce different neighborhoods and global tags to denote different reputation and conformity types, respectively, and discuss the joint effects and heterogeneity of reputation and conformity mechanisms on promoting cooperation in the prisoner's dilemma game. Simulation results show that the joint effects of reputation and conformity mechanisms can promote cooperation effectively and the heterogeneity of these two mechanisms promotes cooperation only in certain circumstances.
Low Skeletal Muscle Mass Accompanied by Abdominal Obesity Additively Increases the Risk of Incident Type 2 Diabetes
Authors: Jun Ji Eun , Lee Seung-Eun , Lee You-Bin , Kim Gyuri , Jin Sang-Man , Jee Jae Hwan , Kim Jae Hyeon
Published: November 2022

Context

Low skeletal muscle mass often accompanies abdominal obesity in the aging process.

Objective

We aimed to investigate the effect of reduced skeletal muscle mass and its interaction with abdominal obesity on incident type 2 diabetes.

Methods

This retrospective longitudinal study included 36 304 diabetes-free Koreans who underwent 2 or more health checkups annually or biannually. Appendicular skeletal muscle mass was measured by bioelectrical impedance analysis and was presented as a skeletal muscle mass index (SMI) adjusted for body weight. Presarcopenia was defined as an SMI less than 1 SD of the sex-specific mean for a healthy young reference group. Abdominal obesity was defined using waist circumference greater than or equal to 90 cm for men and greater than or equal to 85 cm for women. Participants were classified into 4 groups of normal, presarcopenia alone, abdominal obesity alone, and presarcopenic obesity according to initial body composition.

Results

The cumulative incidence of diabetes was 9.1% during the 7-year follow-up. Compared with the highest tertile, the lowest sex-specific SMI tertile was significantly associated with a greater risk of incident type 2 diabetes (adjusted hazard ratio [HR] = 1.31; 95% CI, 1.18-1.45) in a fully adjusted model. Presarcopenic obesity significantly increased incident diabetes risk (adjusted HR = 1.57; 95% CI, 1.42-1.73) compared with normal body composition, presarcopenia alone, or abdominal obesity alone.

Conclusion

Low skeletal muscle mass and its coexistence with abdominal obesity additively increased the risk of incident type 2 diabetes independent of the glycometabolic parameters.
Clinical picture and treatment of myasthenia gravis in the adult population
Authors: Swatko Tomasz , Marzeda Magdalena , Blicharz Agnieszka , Małek Anna , Sygacz Oliwer
Published: November 2022

Introduction and purpose: Myasthenia gravis (MG, myasthenia gravis ) is a classic example of an autoimmune disease caused by antibodies against acetylcholine receptors ( AChR) , muscle-specific kinase (MuSK) or other AChR-related proteins in the postsynaptic muscle membrane leading to characteristic muscle weakness.

Description of the state of knowledge: It is not fully known why the body begins to produce antibodies that act against its own acetylcholine receptors. The main role in producing these antibodies is played by the thymus gland, a gland located in the chest. The thymus gland is normally present in children, while it atrophies in adults. In about 60% of myasthenia gravis patients, however, it is present (we say they have a persistent thymus), and 15% of patients have a thymic neoplasm called a thymoma.

Summary: Myasthenia gravis is the most common neuromuscular junction disorder. Myasthenia gravis is a rare disease that involves muscle weakness of the eyes, pharynx, larynx, respiratory muscles and limbs. Clinical manifestations vary depending on the type of autoantibody and the presence of thymoma.  The diagnosis of the disease should be confirmed by electrodiagnostic and laboratory tests in addition to the typical symptoms.  Myasthenia gravis can manifest at any age, both in men ( peak incidence 50-60 years of age) and women ( peak incidence 20-30 years of age). Muscle fatigue intensifies after any exercise, even small ones. The patient feels best in the morning hours, right after waking up. As time passes, the symptoms of muscle fatigue intensify and the patient becomes less and less fit. For this reason, patients should rest frequently.
A step-by-step decision guide for transanal irrigation: evaluating its usefulness and efficacy in clinical practice
Authors: Emmanuel Anton , Collins Brigitte , Henderson Michelle , Stackhouse Kelly
Published: November 2022

Transanal irrigation (TAI) systems for bowel dysfunction are increasingly used as a management option for patients with constipation or faecal incontinence who fail to adequately improve their symptoms with conservative bowel management. A wide range of products available can make deciding which system to use challenging and overwhelming. The growing use and variety of TAI systems has created the need for guidelines to help clinicians initiating TAI choose the right device for the right patient for the right reasons. Therefore, an evidence-informed decision guide was developed by an expert consensus group to help clinicians make decisions tailored for each individual patient, based on theory and practicalities and promoting safe practice. Feedback from evaluations suggests that this guide is allowing clinicians to access a useful summary to assist consultations and practical discussions.
Clinical digest
Authors: Batas Renata
Published: November 2022

A brief overview of recently published articles on wound, ostomy and continence care
Wound fluid ceftriaxone concentrations after local application with calcium sulphate as carrier material in the treatment of orthopaedic device-associated hip infections
Authors: Wiesli Matthias G. , Livio Françoise , Achermann Yvonne , Gautier Emanuel , Wahl Peter
Published: November 2022

Aims

There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO4) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO4 applied locally to treat ODAI.

Methods

A total of 30 operations with ceftriaxone-loaded CaSO4 had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS).

Results

A total of 37 wound fluid concentrations from 16 operations performed in 14 patients were collected. The ceftriaxone concentrations remained approximately within a range of 100 to 200 mg/l up to three weeks. The median concentration was 108.9 mg/l (interquartile range 98.8 to 142.5) within the first ten days. No systemic adverse reactions were observed.

Conclusion

Our study highlights new clinical data of locally administered ceftriaxone with CaSO4 as carrier material. The near-constant release of ceftriaxone from CaSO4 observed in vitro could be confirmed in vivo. The concentrations remained below known local toxicity thresholds. Cite this article: Bone Joint Res 2022;11(11):835–842.
Construction of a greenhouse prototype with automated control using a low-cost microcontroller and sensors
Authors: Beuter Carlos Henrique , Borges Rafael Cruz , Fogaca Rudiero Cassol
Published: November 2022

Family farming is of fundamental importance for food supply in the domestic market. It is not enough to monitor the data for a better understanding of the entire operational chain by the small producer. It is also necessary to automate the system actuators, allowing better use of natural resources such as water intended for irrigation and reduced operating costs through adequate control of the system’s energy consumption. This article presents the development design and verification of the functionality of an automated system of a greenhouse prototype using low-cost electronic components and simple implementation. The project made it possible to create a database for future conferences by storing data collected in the cloud using the Google Drive platform and data synchronization via Wi-Fi using the ESP32 microcontroller. The prototype’s efficiency and applicability analysis took place over eight days. Data were collected regarding temperature, soil moisture, relative air humidity, water consumption of the irrigation and humidification system, and electricity consumption. The results obtained allowed the verification of the system’s functionality and the ability to store the data on the Google Drive platform, enabling remote consultation through the web server.
Adaptive optics visual simulators: a review of recent optical designs and applications [Invited]
Authors: Marcos Susana , Artal Pablo , Atchison David A. , Hampson Karen , Legras Richard , Lundström Linda , Yoon Geunyoung
Published: November 2022

In their pioneering work demonstrating measurement and full correction of the eye’s optical aberrations, Liang, Williams and Miller, [JOSA A 14, 2884 (1997)10.1364/JOSAA.14.002884] showed improvement in visual performance using adaptive optics (AO). Since then, AO visual simulators have been developed to explore the spatial limits to human vision and as platforms to test non-invasively optical corrections for presbyopia, myopia, or corneal irregularities. These applications have allowed new psychophysics bypassing the optics of the eye, ranging from studying the impact of the interactions of monochromatic and chromatic aberrations on vision to neural adaptation. Other applications address new paradigms of lens designs and corrections of ocular errors. The current paper describes a series of AO visual simulators developed in laboratories around the world, key applications, and current trends and challenges. As the field moves into its second quarter century, new available technologies and a solid reception by the clinical community promise a vigorous and expanding use of AO simulation in years to come.
Holographic Augmented Reality System using Incoherent Holographic Camera and Display
Authors: Kim Youngrok , Son Wonseok , Min Sung-Wook
Published: November 2022

We propose a holographic augmented reality system that can generate and reproduce an incoherent hologram. The augmented hologram consists of optically captured incoherent holograms and computer-generated holograms.
Label-free neural networks-based inverse lithography technology
Authors: Chen Jing-Tao , Zhao Yuan-Yuan , Zhang Yang , Zhu Jian-Xin , Duan Xuan-Ming
Published: November 2022

Neural network-based inverse lithography technology (NNILT) has been used to improve the computational efficiency of large-scale mask optimization for advanced photolithography. NNILT is now mostly based on labels, and its performance is affected by the quality of labels. It is difficult for NNILT to achieve high performance and extrapolation ability for mask optimization without using labels. Here, we propose a label-free NNILT (LF-NNILT), which is implemented completely without labels and greatly improves the printability of the target layouts and the manufacturability of the synthesized masks compared to the traditional ILT. More importantly, the optimization speed of LF-NNILT is two orders of magnitude faster than the traditional ILT. Furthermore, LF-NNILT is simpler to implement and can achieve better solvers to support the development of advanced lithography.
High sensitivity closed-loop Rb optically pumped magnetometer for measuring nuclear magnetization
Authors: Li Siran , Ma Danyue , Wang Kun , Gao Yanan , Xing Bozheng , Fang Xiujie , Han Bangcheng , Quan Wei
Published: November 2022

Rb optically pumped magnetometer (OPM) based on electron paramagnetic resonance (EPR) show advantages to measure the nuclear magnetization and have succeeded in fundamental physics and rotation sensing, etc. The magnetometry sensitivity is a key performance of these Rb OPMs which should be improved. In this study, a high sensitivity Rb OPM is demonstrated theoretically and experimentally. To improve the sensitivity, acousto-optic modulation based on balanced detection is applied to suppress the probe noises. Compared with the conventional optical rotation detection for this OPM configuration, the probe noise shows a significant suppression especially in low frequencies. Eventually, a simultaneous dual-axis transverse measurement with 30 fT/Hz1/2 sensitivity is achieved in a 200 Hz bandwidth and a 250nT linear working range. In addition, we utilize a closed-loop feedback to improve the stability and enlarge the transverse measurement range to 10µT order of magnitude while maintain the open-loop performances. A quasi-static magnetic field measurement can also be achieved in the longitudinal direction in the closed-loop mode. This OPM can serve for the nuclear magnetization measurement with a high sensitivity especially in environments with a large magnitude of the external magnetic field.
Efficient four-wave mixing wavelength conversion in a hybrid silicon slot and polymer microring resonator
Authors: Hong Jianxun , Rokumyo Kenta , Mao Jiawei , Bannaron Alisa , Sato Hiromu , Yokoyama Shiyoshi
Published: November 2022

We present a silicon slot microring resonator for efficient frequency conversion via four-wave mixing (FWM). The slot consists of a narrow silicon waveguide pair with a gap of 80 nm, which is filled with a nonlinear optical polymer. The group velocity dispersion for the microring is controlled by engineering the geometry of the slot structure. Because of the large buildup factor of the slot microring, an FWM conversion efficiency of −27.4 dB is achieved with an optical pump power of less than 1.0 mW. From the measured power dependence of FWM generation, a nonlinear refractive index coefficient of 1.31 × 10−17 m2 W−1 is obtained at a wavelength of 1562 nm. This work presents a hybrid silicon slot and polymer microring as a potential nonlinear device for applications in integrated photonic devices.
All-optical information conversion in Rb vapor based on the spatial cross-phase modulation
Authors: Wang Sandan , Yuan Jinpeng , Wang Lirong , Xiao Liantuan , Jia Suotang
Published: November 2022

All-optical information conversion, conveying optical signals without electro-optical transformation, plays a vital role in the all-optical devices and optical communication. We achieve the all-optical information conversion in Rb vapor by utilizing the spatial cross-phase modulation. The refractive index of atomic medium is spatially modulated by the strong switch laser beam, which makes it as a nonlinear focusing lens for the weak signal laser beam. As a result, the far-field diffraction ring patterns of the signal laser beam interacted with atoms can effectively carry the nonlinear phase shift information of the switch laser beam. The channel numbers, channel capacities and channel storage densities of information transmission from switch laser beam to signal laser beam are investigated in the terms of switch laser intensity and vapor temperature. Finally, a special “sxu” alphabetic string, encoded by ASCII code, is introduced to verify this all-optical information conversion scheme. This work paves the way for studying optical information processing and all-optical networking with atomic ensembles.
PTRN-1 (CAMSAP) and NOCA-2 (NINEIN) are required for microtubule polarity in Caenorhabditis elegans dendrites
Authors: He Liu , van Beem Lotte , Snel Berend , Hoogenraad Casper C. , Harterink Martin
Published: November 2022

The neuronal microtubule cytoskeleton is key to establish axon-dendrite polarity. Dendrites are characterized by the presence of minus-end out microtubules. However, the mechanisms that organize these microtubules with the correct orientation are still poorly understood. UsingCaenorhabditis elegansas a model system for microtubule organization, we characterized the role of 2 microtubule minus-end related proteins in this process, the microtubule minus-end stabilizing protein calmodulin-regulated spectrin-associatedprotein(CAMSAP/PTRN-1), and the NINEIN homologue, NOCA-2 (noncentrosomal microtubule array). We found that CAMSAP and NINEIN function in parallel to mediate microtubule organization in dendrites. During dendrite outgrowth, RAB-11-positive vesicles localized to the dendrite tip to nucleate microtubules and function as a microtubule organizing center (MTOC). In the absence of either CAMSAP or NINEIN, we observed a low penetrance MTOC vesicles mislocalization to the cell body, and a nearly fully penetrant phenotype in double mutant animals. This suggests that both proteins are important for localizing the MTOC vesicles to the growing dendrite tip to organize microtubules minus-end out. Whereas NINEIN localizes to the MTOC vesicles where it is important for the recruitment of the microtubule nucleator γ-tubulin, CAMSAP localizes around the MTOC vesicles and is cotranslocated forward with the MTOC vesicles upon dendritic growth. Together, these results indicate that microtubule nucleation from the MTOC vesicles and microtubule stabilization are both important to localize the MTOC vesicles distally to organize dendritic microtubules minus-end out.
Human striatal organoids derived from pluripotent stem cells recapitulate striatal development and compartments
Authors: Chen Xinyu , Saiyin Hexige , Liu Yang , Wang Yuqi , Li Xuan , Ji Rong , Ma Lixiang
Published: November 2022

The striatum links neuronal circuits in the human brain, and its malfunction causes neuronal disorders such as Huntington’s disease (HD). A human striatum model that recapitulates fetal striatal development is vital to decoding the pathogenesis of striatum-related neurological disorders and developing therapeutic strategies. Here, we developed a method to construct human striatal organoids (hStrOs) from human pluripotent stem cells (hPSCs), including hStrOs-derived assembloids. Our hStrOs partially replicated the fetal striatum and formed striosome and matrix-like compartments in vitro. Single-cell RNA sequencing revealed distinct striatal lineages in hStrOs, diverging from dorsal forebrain fate. Using hStrOs-derived assembloids, we replicated the striatal targeting projections from different brain parts. Furthermore, hStrOs can serve as hosts for striatal neuronal allografts to test allograft neuronal survival and functional integration. Our hStrOs are suitable for studying striatal development and related disorders, characterizing the neural circuitry between different brain regions, and testing therapeutic strategies.
A qualitative study of the barriers to using blinding in in vivo experiments and suggestions for improvement
Authors: Karp Natasha A. , Pearl Esther J. , Stringer Emma J. , Barkus Chris , Ulrichsen Jane Coates , Percie du Sert Nathalie
Published: November 2022

In animal experiments, blinding (also known as masking) is a methodological strategy to reduce the risk that scientists, animal care staff, or other staff involved in the research may consciously or subconsciously influence the outcome. Lack of masking has been shown to correlate with an overestimation of treatment efficacy and false positive findings. We conducted exploratory interviews across academic and a commercial setting to discuss the implementation of masking at four stages of the experiment: during allocation and intervention, during the conduct of the experiment, during the outcome assessment, and during the data analysis. The objective was to explore the awareness, engagement, perceptions, and the barriers to implementing masking in animal experiments. We conducted multiple interviews, to explore 30 different experiments, and found examples of excellent practice but also areas where masking was rarely implemented. Significant barriers arose from the operational and informatic systems implemented. These systems have prioritised the management of welfare without considering how to allow researchers to use masking in their experiments. For some experiments, there was a conflict between the management of welfare for an individual animal versus delivering a robust experiment where all animals are treated in the same manner. We identified other challenges related to the level of knowledge on the purpose of masking or the implementation and the work culture. The exploration of these issues provides insight into how we, as a community, can identify the most significant barriers in a given research environment. Here, we offer practical solutions to enable researchers to implement masking as standard. To move forward, we need both the individual scientists to embrace the use of masking and the facility managers and institutes to engage and provide a framework that supports the scientists.
The pan-genome of Aspergillus fumigatus provides a high-resolution view of its population structure revealing high levels of lineage-specific diversity driven by recombination
Authors: Lofgren Lotus A. , Ross Brandon S. , Cramer Robert A. , Stajich Jason E.
Published: November 2022

Aspergillus fumigatusis a deadly agent of human fungal disease where virulence heterogeneity is thought to be at least partially structured by genetic variation between strains. While population genomic analyses based on reference genome alignments offer valuable insights into how gene variants are distributed across populations, these approaches fail to capture intraspecific variation in genes absent from the reference genome. Pan-genomic analyses based on de novo assemblies offer a promising alternative to reference-based genomics with the potential to address the full genetic repertoire of a species. Here, we evaluate 260 genome sequences ofA.fumigatusincluding 62 newly sequenced strains, using a combination of population genomics, phylogenomics, and pan-genomics. Our results offer a high-resolution assessment of population structure and recombination frequency, phylogenetically structured gene presence–absence variation, evidence for metabolic specificity, and the distribution of putative antifungal resistance genes. AlthoughA.fumigatusdisperses primarily via asexual conidia, we identified extraordinarily high levels of recombination with the lowest linkage disequilibrium decay value reported for any fungal species to date. We provide evidence for 3 primary populations ofA.fumigatus, with recombination occurring only rarely between populations and often within them. These 3 populations are structured by both gene variation and distinct patterns of gene presence–absence with unique suites of accessory genes present exclusively in each clade. Accessory genes displayed functional enrichment for nitrogen and carbohydrate metabolism suggesting that populations may be stratified by environmental niche specialization. Similarly, the distribution of antifungal resistance genes and resistance alleles were often structured by phylogeny. Altogether, the pan-genome ofA.fumigatusrepresents one of the largest fungal pan-genomes reported to date including many genes unrepresented in the Af293 reference genome. These results highlight the inadequacy of relying on a single-reference genome-based approach for evaluating intraspecific variation and the power of combined genomic approaches to elucidate population structure, genetic diversity, and putative ecological drivers of clinically relevant fungi.
A neurocomputational theory of action regulation predicts motor behavior in neurotypical individuals and patients with Parkinson’s disease
Authors: Zhong Shan , Choi Jeong Woo , Hashoush Nadia G. , Babayan Diana , Malekmohammadi Mahsa , Pouratian Nader , Christopoulos Vassilios
Published: November 2022

Surviving in an uncertain environment requires not only the ability to select the best action, but also the flexibility to withhold inappropriate actions when the environmental conditions change. Although selecting and withholding actions have been extensively studied in both human and animals, there is still lack of consensus on the mechanism underlying these action regulation functions, and more importantly, how they inter-relate. A critical gap impeding progress is the lack of a computational theory that will integrate the mechanisms of action regulation into a unified framework. The current study aims to advance our understanding by developing a neurodynamical computational theory that models the mechanism of action regulation that involves suppressing responses, and predicts how disruption of this mechanism can lead to motor deficits in Parkinson’s disease (PD) patients. We tested the model predictions in neurotypical individuals and PD patients in three behavioral tasks that involve free action selection between two opposed directions, action selection in the presence of conflicting information and abandoning an ongoing action when a stop signal is presented. Our results and theory suggest an integrated mechanism of action regulation that affects both action initiation and inhibition. When this mechanism is disrupted, motor behavior is affected, leading to longer reaction times and higher error rates in action inhibition.
Soft disorder modulates the assembly path of protein complexes
Authors: Seoane Beatriz , Carbone Alessandra
Published: November 2022

The relationship between interactions, flexibility and disorder in proteins has been explored from many angles over the years: folding upon binding, flexibility of the core relative to the periphery, entropy changes, etc. In this work, we provide statistical evidence for the involvement of highly mobile and disordered regions in complex assembly. We ordered the entire set of X-ray crystallographic structures in the Protein Data Bank into hierarchies of progressive interactions involving identical or very similar protein chains, yielding 40205 hierarchies of protein complexes with increasing numbers of partners. We then examine them as proxies for the assembly pathways. Using this database, we show that upon oligomerisation, the new interfaces tend to be observed at residues that were characterised as softly disordered (flexible, amorphous or missing residues) in the complexes preceding them in the hierarchy. We also rule out the possibility that this correlation is just a surface effect by restricting the analysis to residues on the surface of the complexes. Interestingly, we find that the location of soft disordered residues in the sequence changes as the number of partners increases. Our results show that there is a general mechanism for protein assembly that involves soft disorder and modulates the way protein complexes are assembled. This work highlights the difficulty of predicting the structure of large protein complexes from sequence and emphasises the importance of linking predictors of soft disorder to the next generation of predictors of complex structure. Finally, we investigate the relationship between the Alphafold2’s confidence metric pLDDT for structure prediction in unbound versus bound structures, and soft disorder. We show a strong correlation between Alphafold2 low confidence residues and the union of all regions of soft disorder observed in the hierarchy. This paves the way for using the pLDDT metric as a proxy for predicting interfaces and assembly paths.
Education interacts with genetic variants near GJD2, RBFOX1, LAMA2, KCNQ5 and LRRC4C to confer susceptibility to myopia
Authors: Clark Rosie , Pozarickij Alfred , Hysi Pirro G. , Ohno-Matsui Kyoko , Williams Cathy , Guggenheim Jeremy A. ,   UK Biobank Eye and Vision Consortium
Published: November 2022

Myopia most often develops during school age, with the highest incidence in countries with intensive education systems. Interactions between genetic variants and educational exposure are hypothesized to confer susceptibility to myopia, but few such interactions have been identified. Here, we aimed to identify genetic variants that interact with education level to confer susceptibility to myopia. Two groups of unrelated participants of European ancestry from UK Biobank were studied. A ‘Stage-I’ sample of 88,334 participants whose refractive error (avMSE) was measured by autorefraction and a ‘Stage-II’ sample of 252,838 participants who self-reported their age-of-onset of spectacle wear (AOSW) but who did not undergo autorefraction. Genetic variants were prioritized via a 2-step screening process in the Stage-I sample: Step 1 was a genome-wide association study for avMSE; Step 2 was a variance heterogeneity analysis for avMSE. Genotype-by-education interaction tests were performed in the Stage-II sample, with University education coded as a binary exposure. On average, participants were 58 years-old and left full-time education when they were 18 years-old; 35% reported University level education. The 2-step screening strategy in the Stage-I sample prioritized 25 genetic variants (GWAS P < 1e-04; variance heterogeneity P < 5e-05). In the Stage-II sample, 19 of the 25 (76%) genetic variants demonstrated evidence of variance heterogeneity, suggesting the majority were true positives. Five genetic variants located near GJD2, RBFOX1, LAMA2, KCNQ5 and LRRC4C had evidence of a genotype-by-education interaction in the Stage-II sample (P < 0.002) and consistent evidence of a genotype-by-education interaction in the Stage-I sample. For all 5 variants, University-level education was associated with an increased effect of the risk allele. In this cohort, additional years of education were associated with an enhanced effect of genetic variants that have roles including axon guidance and the development of neuronal synapses and neural circuits.
Divergent gene expression responses in two Baltic Sea heterotrophic model bacteria to dinoflagellate dissolved organic matter
Authors: Osbeck Christofer M. G. , Lundin Daniel , Karlsson Camilla , Teikari Jonna E. , Moran Mary Ann , Pinhassi Jarone
Published: November 2022

Phytoplankton release massive amounts of dissolved organic matter (DOM) into the water column during recurring blooms in coastal waters and inland seas. The released DOM encompasses a complex mixture of both known and unknown compounds, and is a rich nutrient source for heterotrophic bacteria. The metabolic activity of bacteria during and after phytoplankton blooms can hence be expected to reflect the characteristics of the released DOM. We therefore investigated if bacterioplankton could be used as “living sensors” of phytoplankton DOM quantity and/or quality, by applying gene expression analyses to identify bacterial metabolisms induced by DOM. We used transcriptional analysis of two Baltic Sea bacterial isolates (Polaribactersp. BAL334 [Flavobacteriia] andBrevundimonassp. BAL450 [Alphaproteobacteria]) growing with DOM from axenic cultures of the dinoflagellateProrocentrum minimum. We observed pronounced differences between the two bacteria both in growth and the expressed metabolic pathways in cultures exposed to dinoflagellate DOM compared with controls. Differences in metabolic responses between the two isolates were caused both by differences in gene repertoire between them (e.g. in the SEED categories for membrane transport, motility and photoheterotrophy) and the regulation of expression (e.g. fatty acid metabolism), emphasizing the importance of separating the responses of different taxa in analyses of community sequence data. Similarities between the bacteria included substantially increased expression of genes for Ton and Tol transport systems in both isolates, which are commonly associated with uptake of complex organic molecules.Polaribactersp. BAL334 showed stronger metabolic responses to DOM harvested from exponential than stationary phase dinoflagellates (128 compared to 26 differentially expressed genes), whereasBrevundimonassp. BAL450 responded more to the DOM from stationary than exponential phase dinoflagellates (33 compared to 6 differentially expressed genes). These findings suggest that shifts in bacterial metabolisms during different phases of phytoplankton blooms can be detected in individual bacterial species and can provide insights into their involvement in DOM transformations.
NGSpop: A desktop software that supports population studies by identifying sequence variations from next-generation sequencing data
Authors: Lee Dong-Jun , Kwon Taesoo , Lee Hye-Jin , Oh Yun-Ho , Kim Jin-Hyun , Lee Tae-Ho
Published: November 2022

Next-generation sequencing (NGS) is widely used in all areas of genetic research, such as genetic disease diagnosis and breeding, and it can produce massive amounts of data. The identification of sequence variants is an important step when processing large NGS datasets; however, currently, the process is complicated, repetitive, and requires concentration, which can be taxing on the researcher. Therefore, to support researchers who are not familiar enough with bioinformatics to identify sequence variations regularly from large datasets, we have developed a fully automated desktop software, NGSpop. NGSpop includes functionalities for all the variant calling and visualization procedures used when processing NGS data, such as quality control, mapping, filtering details, and variant calling. In the variant calling step, the user can select the GATK or DeepVariant algorithm for variant calling. These algorithms can be executed using pre-set pipelines and options or customized with the user-specified options. NGSpop is implemented using JavaFX (version 1.8) and can thus be run on Unix-like operating systems such as Ubuntu Linux (version 16.04, 18.0.4). Although several pipelines and visualization tools are available for NGS data analysis, most integrated environments do not support batch processes; thus, variant detection cannot be automated for population-level studies. The NGSpop software developed in this study has an easy-to-use interface and helps in rapid analysis of multiple NGS data from population studies. According to a benchmark test, it effectively reduced the carbon footprint in bioinformatics analysis by expending the least central processing unit heat and power. Additionally, this software makes it possible to use the GATK and DeepVariant algorithms more flexibly and efficiently than other programs by allowing users to choose between the algorithms. As a limitation, NGSpop currently supports only the sequencing reads in fastq format produced by the Illumina platform. NGSpop is freely available at https://sourceforge.net/projects/ngspop/.
Diabetes medications and associations with Covid-19 outcomes in the N3C database: A national retrospective cohort study
Authors: Bramante Carolyn T. , Johnson Steven G. , Garcia Victor , Evans Michael D. , Harper Jeremy , Wilkins Kenneth J. , Huling Jared D. , Mehta Hemalkumar , Alexander Caleb , Tronieri Jena , Hong Stephenie , Kahkoska Anna , Alamgir Joy , Koraishy Farrukh , Hartman Katrina , Yang Kaifeng , Abrahamsen Trine , Stürmer Til , Buse John B. ,   N3C core authors
Published: November 2022

Background

While vaccination is the most important way to combat the SARS-CoV-2 pandemic, there may still be a need for early outpatient treatment that is safe, inexpensive, and currently widely available in parts of the world that do not have access to the vaccine. There are in-silico, in-vitro, and in-tissue data suggesting that metformin inhibits the viral life cycle, as well as observational data suggesting that metformin use before infection with SARS-CoV2 is associated with less severe COVID-19. Previous observational analyses from single-center cohorts have been limited by size.

Methods

Conducted a retrospective cohort analysis in adults with type 2 diabetes (T2DM) for associations between metformin use and COVID-19 outcomes with an active comparator design of prevalent users of therapeutically equivalent diabetes monotherapy: metformin versus dipeptidyl-peptidase-4-inhibitors (DPP4i) and sulfonylureas (SU). This took place in the National COVID Cohort Collaborative (N3C) longitudinal U.S. cohort of adults with +SARS-CoV-2 result between January 1 2020 to June 1 2021. Findings included hospitalization or ventilation or mortality from COVID-19. Back pain was assessed as a negative control outcome.

Results

6,626 adults with T2DM and +SARS-CoV-2 from 36 sites. Mean age was 60.7 +/- 12.0 years; 48.7% male; 56.7% White, 21.9% Black, 3.5% Asian, and 16.7% Latinx. Mean BMI was 34.1 +/- 7.8kg/m2. Overall 14.5% of the sample was hospitalized; 1.5% received mechanical ventilation; and 1.8% died. In adjusted outcomes, compared to DPP4i, metformin had non-significant associations with reduced need for ventilation (RR 0.68, 0.32–1.44), and mortality (RR 0.82, 0.41–1.64). Compared to SU, metformin was associated with a lower risk of ventilation (RR 0.5, 95% CI 0.28–0.98, p = 0.044) and mortality (RR 0.56, 95%CI 0.33–0.97, p = 0.037). There was no difference in unadjusted or adjusted results of the negative control.

Conclusions

There were clinically significant associations between metformin use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.
Incidence of HIV infection and associated factors among female sex workers in Côte d’Ivoire, results of the ANRS 12361 PrEP-CI study using recent infection assays
Authors: Nouaman Marcellin N. , Becquet Valentine , Plazy Mélanie , Coffie Patrick A. , Zébago Clémence , Montoyo Alice , Anoma Camille , Eholié Serge , Dabis François , Larmarange Joseph ,   for the ANRS 12361 PrEP-CI Study group
Published: November 2022

Background

This study aimed to estimate, using an HIV Recent Infection Testing Algorithm (RITA), the HIV incidence and its associated factors among female sex workers (FSW) in Côte d’Ivoire.

Methods

A cross-sectional study was conducted in 2016–2017 in Abidjan and San Pedro’s region among FSW aged ≥ 18 years. In addition, a sociodemographic questionnaire, HIV screening was carried out by two rapid tests. In the event of a positive result, a dried blood spot sample was taken to determine, using a RITA adapted to the Ivorian context, if it was a recent HIV infection.

Results

A total of 1000 FSW were surveyed with a median age of 25 years (interquartile range: 21–29 years). 39 (3.9%) tested positive for HIV. The incidence of HIV was estimated to be 2.3 per 100 person-years, with higher incidence rates among those 24 years old or less (3.0% vs. 1.9%), non-Ivorian FSW (3.2% vs. 1.9%) and those with the lowest education level (4.6% in FSW who never went to school vs. 2.6%). The incidence seemed to be associated with the sex work practice conditions: higher incidence among FSW whose usual price was less than 3.50$ (4.3% vs.1.0%), FSW who had a larger number of clients on the last day of work (6.1% in those with 7 clients or more vs. 1.8%), FSW who reported not always using condoms with their clients (8.5% vs. 1.5%) and FSW who reported agreeing to sex without a condom in exchange for a large sum of money (10.1% vs. 1.2%).

Conclusion

This study confirms that FSW remain highly exposed to HIV infection. Exposure to HIV is also clearly associated with certain sex-work factors and the material conditions of sex work. Efforts in the fight against HIV infection must be intensified to reduce new infections among FSW.
Starting the SToP trial: Lessons from a collaborative recruitment approach
Authors: McRae Tracy , Walker Roz , Jacky John , Katzenellenbogen Judith M. , Coffin Juli , Christophers Ray , Carapetis Jonathan , Bowen Asha C.
Published: November 2022

Objective

Recruitment in research can be challenging in Australian Aboriginal contexts. We aimed to evaluate the SToP (See, Treat, Prevent skin infections) trial recruitment approach for Aboriginal families to identify barriers and facilitators and understand the utility of the visual resource used.

Methods

This qualitative participatory action research used purposive sampling to conduct six semi-structured interviews with staff and five yarning sessions with Aboriginal community members from the nine communities involved in the SToP trial that were audio recorded and transcribed verbatim before thematic analysis.

Findings

Community members valued the employment of local Aboriginal facilitators who used the flipchart to clearly explain the importance of healthy skin and the rationale for the SToP trial while conducting recruitment. A prolonged process, under-developed administrative systems and stigma of the research topic emerged as barriers.

Conclusion

Partnering with a local Aboriginal organisation, employing Aboriginal researchers, and utilising flip charts for recruitment was seen by some as successful. Strengthening governance with more planning and support for recordkeeping emerged as future success factors.

Implications for public health

Our findings validate the importance of partnership for this critical phase of a research project. Recruitment strategies should be co-designed with Aboriginal research partners. Further, recruitment rates for the SToP trial provide a firm foundation for building partnerships between organisations and ensuring Aboriginal perspectives determine recruitment methods.
A box on the river: The phylogenetics and phylogeography of Eucalyptus baueriana (Eucalyptus sect. Adnataria ser. Heterophloiae)
Authors: Fahey Patrick S. , Udovicic Frank , Cantrill David J. , Bayly Michael J.
Published: November 2022

We present a phylogeographic study of the tree speciesEucalyptus bauerianaSchauer, which occurs in disjunct areas on the near coastal plains and ranges of the south-east Australian mainland. DArTseq data are used to build a phylogeny includingE.bauerianaand closely related taxa to test its monophyly, test the genetic distinctness of the three subspecies ofE.baueriana, and investigate relationships between its disjunct populations. Additionally, we use population structure analysis to investigate the genetic distinctness of populations, and MaxEnt to investigate the environmental factors potentially influencing the species’ distribution. We showE.bauerianais monophyletic and most closely related to three other Blue Box eucalypt species:E.conicaH.Deane & Maiden,E.dalveenicaT.L.Collins, R.L.Andrew & J.J.Bruhl andE.magnificataL.A.S.Johnson & K.D.Hill, with some evidence for genetic introgression between these taxa. WithinE.baueriana, the deepest genetic breaks do not correspond with the subspecies classification as the two geographically restricted subspecies, together with samples of the more widespreadE.bauerianasubsp.bauerianafrom west of the Gippsland lowlands, form a south-western clade with that is sister to other populations of subsp.baueriana. The oldest genetic break in the species occurs in far eastern Gippsland (Victoria), corresponding to one of the shortest geographic disjunctions in the species’ distribution. Genetic breaks in other species have been observed in this region which is broadly referred to as the southern transition zone. Both total annual rainfall and the seasonality of this rainfall are hypothesised to affect the species’ distribution; gaps in its distribution are in areas of higher rainfall that support closed forest and in regions with more winter dominated rainfall.