bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating high-speed liquid impingement with full-field measurements
Authors: Burson-Thomas C. B. , Harvey T. J. , Fletcher L. , Wellman R. , Pierron F. , Wood R. J. K.
Published: September 2023

Repeated high-speed liquid impingement on solid surfaces results in erosion that can have undesirable consequences. In recent years, the capacity of model predictions has exceeded the experimental measurements of an impingement; this work closes the gap. Using the grid method, tens of thousands of individual measurements of surface displacement were taken of the response of a polymethylmethacrylate test specimen to the impingement of a high-speed (

233

 

m
 
s

−
1

) curved-fronted water jet. The full-field measurements were taken at a rate of 5 MHz and interpreted using two models based on differing sets of assumptions. The results support the current qualitative description of a high-speed impingement. However, the widespread assumption of a rigid solid surface in existing analysis and modelling was found to be inaccurate: only the model that recognized the effect of the compliance of the solid surface was successful in predicting the measured temporal and spatial variation in displacement and acceleration. This model predicted that the energy absorbed by the solid surface was less than 0.3% of the total kinetic energy of the equivalent droplet impingement.
Exact solutions to fall of particle to singular potential: classical versus quantum cases
Authors: Tribelsky Michael I.
Published: September 2023

Exact solutions describing a fall of a particle to the centre of a non-regularized singular potential in classical and quantum cases are obtained and compared. We inspect the quantum problem with the help of the conventional Schrödinger’s equation. During the fall, the wave function spatial localization area contracts into a single zero-dimensional point. For the fall-admitting potentials, the Hamiltonian is non-Hermitian. Because of that, the wave function norm occurs time-dependent. It demands an extension to this case of the continuity equation and rules for mean value calculations. Surprisingly, the quantum and classical solutions exhibit striking similarities. In particular, both are self-similar as the particle energy equals zero. The characteristic spatial scales of the quantum and classical self-similar solutions obey the same temporal dependence. We present arguments indicating that these self-similar solutions are attractors to a broader class of solutions, describing the fall at finite energy of the particle.
Competition and habitat availability interact to structure arboreal ant communities across scales of ecological organization
Authors: Adams Benjamin J. , Gora Evan M. , Donaldson-Matasci Matina C. , Robinson Elva J. H. , Powell Scott
Published: September 2023

Understanding how resource limitation and biotic interactions interact across spatial scales is fundamental to explaining the structure of ecological communities. However, empirical studies addressing this issue are often hindered by logistical constraints, especially at local scales. Here, we use a highly tractable arboreal ant study system to explore the interactive effects of resource availability and competition on community structure across three local scales: an individual tree, the nest network created by each colony and the individual ant nest. On individual trees, the ant assemblages are primarily shaped by availability of dead wood, a critical nesting resource. The nest networks within a tree are constrained by the availability of nesting resources but also influenced by the co-occurring species. Within individual nests, the distribution of adult ants is only affected by distance to interspecific competitors. These findings demonstrate that resource limitation exerts the strongest effects on diversity at higher levels of local ecological organization, transitioning to a stronger effect of species interactions at finer scales. Collectively, these results highlight that the process exerting the strongest influence on community structure is highly dependent on the scale at which we examine the community, with shifts occurring even across fine-grained local scales.
Holocene deglaciation drove rapid genetic diversification of Atlantic walrus
Authors: Ruiz-Puerta Emily J. , Keighley Xénia , Desjardins Sean P. A. , Gotfredsen Anne Birgitte , Pan Shyong En , Star Bastiaan , Boessenkool Sanne , Barrett James H. , McCarthy Morgan L. , Andersen Liselotte W. , Born Erik W. , Howse Lesley R. , Szpak Paul , Pálsson Snæbjörn , Malmquist Hilmar J. , Rufolo Scott , Jordan Peter D. , Olsen Morten Tange
Published: September 2023

Rapid global warming is severely impacting Arctic ecosystems and is predicted to transform the abundance, distribution and genetic diversity of Arctic species, though these linkages are poorly understood. We address this gap in knowledge using palaeogenomics to examine how earlier periods of global warming influenced the genetic diversity of Atlantic walrus (
Odobenus rosmarus rosmarus
), a species closely associated with sea ice and shallow-water habitats. We analysed 82 ancient and historical Atlantic walrus mitochondrial genomes (mitogenomes), including now-extinct populations in Iceland and the Canadian Maritimes, to reconstruct the Atlantic walrus' response to Arctic deglaciation. Our results demonstrate that the phylogeography and genetic diversity of Atlantic walrus populations was initially shaped by the last glacial maximum (LGM), surviving in distinct glacial refugia, and subsequently expanding rapidly in multiple migration waves during the late Pleistocene and early Holocene. The timing of diversification and establishment of distinct populations corresponds closely with the chronology of the glacial retreat, pointing to a strong link between walrus phylogeography and sea ice. Our results indicate that accelerated ice loss in the modern Arctic may trigger further dispersal events, likely increasing the connectivity of northern stocks while isolating more southerly stocks putatively caught in small pockets of suitable habitat.
Consistent changes in muscle metabolism underlie dive performance across multiple lineages of diving ducks
Authors: Schell Elizabeth R. , McCracken Kevin G. , Scott Graham R. , White Jeff , Lavretsky Philip , Dawson Neal J.
Published: September 2023

Diving animals must sustain high activity with limited O
2
stores to successfully capture prey. Studies suggest that increasing body O
2
stores supports breath-hold diving, but less is known about metabolic specializations that underlie underwater locomotion. We measured maximal activities of 10 key enzymes in locomotory muscles (gastrocnemius and pectoralis) to identify biochemical changes associated with diving in pathways of oxidative and substrate-level phosphorylation and compared them across three groups of ducks—the longest diving sea ducks (eight spp.), the mid-tier diving pochards (three spp.) and the non-diving dabblers (five spp.). Relative to dabblers, both diving groups had increased activities of succinate dehydrogenase and cytochrome c oxidase, and sea ducks further showed increases in citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase (HOAD). Both diving groups had relative decreases in capacity for anaerobic metabolism (lower ratio of lactate dehydrogenase to CS), with sea ducks also showing a greater capacity for oxidative phosphorylation and lipid oxidation (lower ratio of pyruvate kinase to CS, higher ratio of HOAD to hexokinase). These data suggest that the locomotory muscles of diving ducks are specialized for sustaining high rates of aerobic metabolism, emphasizing the importance of body O
2
stores for dive performance in these species.
Nocardioides pini sp. nov. and Nocardioides pinisoli sp. nov., two novel actinomycetes isolated from Pinus densiflora
Authors: So Yoonseop , Chhetri Geeta , Kim Inhyup , Park Sunho , Jung Yonghee , Woo Haejin , Seo Taegun
Published: September 2023

Two novel Gram-positive bacteria designated as strains STR2Tand STR3Twere isolated from the rhizosphere of aPinus densiflorasample collected from Goyang-si, Republic of Korea. Strains STR2Tand STR3Twere aerobic, rod shaped, non-sporulated, catalase negative, oxidase negative and non-motile bacteria. They grew at 15–37 °C (optimum, 25–30 °C), at pH 6.0–11.0 (optimum, pH 7.0) and in the presence of 0–2% NaCl (optimum, 0 %, w/v). The chemotaxonomic and morphological characteristics of the novel strains were consistent with those of the members ofNocardioides. The phylogenetic analysis of the 16S rRNA gene sequences revealed that STR2Twas closely related toN. cavernaeYIM A1136T(99.3 %) andN. flavusY4T(99.1 %), and STR3Twas closely related toN. exalbidusDSM 22017T(99.0 %),N. baculatusG10T(98.8 %) andN. hwasunensisHFW-21T(98.7 %). The average nucleotide identity, average amino acid identity and digital DNA–DNA hybridization values of STR2Tand STR3Twith the most closely related strains that have publicly available whole genomes were 83.1–89.8 %, 80.9–89.6% and 26.2–39.1 %, respectively. The cell-wall peptidoglycan of strain STR2Tand STR3Tcontainedll-diaminopimelic acid as the diagnostic amino acid. The major fatty acids in STR2Tand STR3Twere iso-C16 : 0and C17 : 1 ω8c, and the predominant quinone was MK-8(H4). Their polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and other polar lipids. The draft genome sequences showed that the genomic DNA G+C content of STR2Tand STR3Twere both 72.2 mol%. Physiological and biochemical tests and 16S rRNA sequence analysis clearly revealed that STR2Tand STR3Tcould represent novelNocardioidesspecies. Their proposed names were as follows:Nocardioides pinisp. nov. for strain STR2T(=KACC 22784T=TBRC 16336T) andNocardioides pinisolisp. nov. for strain STR3T(= KACC 22785T=TBRC 16337T).
Acquisition of Type I methyltransferase via horizontal gene transfer increases the drug resistance of Aeromonas veronii
Authors: Ma Jiayue , Zhao Honghao , Mo Shuangyi , Li Juanjuan , Ma Xiang , Tang Yanqiong , Li Hong , Liu Zhu
Published: September 2023

Aeromonas veronii

is an opportunistic pathogen that affects both fish and mammals, including humans, leading to bacteraemia, sepsis, meningitis and even death. The increasing virulence and drug resistance of

A. veronii

are of significant concern and pose a severe risk to public safety. The Type I restriction-modification (RM) system, which functions as a bacterial defence mechanism, can influence gene expression through DNA methylation. However, little research has been conducted to explore its origin, evolutionary path, and relationship to virulence and drug resistance in

A. veronii

. In this study, we analysed the pan-genome of 233

A

.

veronii

strains, and the results indicated that it was 'open', meaning that

A. veronii

has acquired additional genes from other species. This suggested that

A. veronii

had the potential to adapt and evolve rapidly, which might have contributed to its drug resistance. One Type I methyltransferase (MTase) and two complete Type I RM systems were identified, namely AveC4I, AveC4II and AveC4III in

A. veronii

strain C4, respectively. Notably, AveC4I was exclusive to

A. veronii

C4. Phylogenetic analysis revealed that AveC4I was derived from horizontal gene transfer from

Thiocystis violascens

and exchanged genes with the human pathogen

Comamonas kerstersii

. Single molecule real-time sequencing was applied to identify the motif methylated by AveC4I, which was unique and not recognized by any reported MTases in the REBASE database. We also annotated the functions and pathways of the genes containing the motif, revealing that AveC4I may control drug resistance in

A. veronii

C4. Our findings provide new insight on the mechanisms underlying drug resistance in pathogenic bacteria. By identifying the specific genes and pathways affected by AveC4I, this study may aid in the development of new therapeutic approaches to combat

A. veronii

infections.
Expanding the DNA editing toolbox: novel lambda integrase variants targeting microalgal and human genome sequences
Authors: Wei Siau Jia , Siddiqui Asim Azhar , Yi Lau Sze , Kannan inivasaraghavan , Peter Sabrina , Yingying Zeng , Verma Chandra , Droge Peter , Ghadessy John F.
Published: September 2023

Recombinase enzymes are extremely efficient at integrating very large DNA fragments into target genomes. However, intrinsic sequence specificities curtail their use to DNA sequences with sufficient homology to endogenous target motifs. Extensive engineering is therefore required to broaden applicability and robustness. Here, we describe the directed evolution of novel lambda integrase variants capable of editing exogenous target sequences identified in the diatomPhaeodactylum tricornutumand the algaeNannochloropsis oceanica. These microorganisms hold great promise as conduits for green biomanufacturing and carbon sequestration. The evolved enzyme variants show >1000-fold switch in specificity towards the non-natural target sites when assayedin vitro. A single-copy target motif in the human genome with homology to theNannochloropsis oceanicasite can also be efficiently targeted using an engineered integrase, bothin vitroand in human cells. The developed integrase variants represent useful additions to the DNA editing toolbox, with particular application for targeted genomic insertion of large DNA cargos.
Genome Report: Chromosome-scale Genome Assembly of the West Indian fruit flyAnastrepha obliqua(Diptera: Tephritidae)
Authors: Sim Sheina B. , Congrains Carlos , Velasco-Cuervo Sandra M. , Corpuz Renee L. , Kauwe Angela N. , Scheffler Brian , Geib Scott M.
Published: September 2023

The West Indian fruit fly,Anastrepha obliqua, is a major pest of mango in Central and South America and attacks more than 60 species of host fruits. To support current genetic and genomic research onA. obliqua, we sequenced the genome using high-fidelity (HiFi) long-read sequencing. This resulted in a highly contiguous contig assembly with 90% of the genome in 10 contigs. The contig assembly was placed in a chromosomal context using synteny with a closely related species,A. ludens, as both are members of theA. fraterculusgroup. The resulting assembly represents the five autosomes and the X chromosome which represents 95.9% of the genome, and 199 unplaced contigs representing the remaining 4.1%. Orthology analysis across the structural annotation sets of high quality tephritid genomes demonstrates the gene annotations are robust, and identified genes unique toAnastrephaspecies that may help define their pestiferous nature that can be used as a starting point for comparative genomics. This genome assembly represents the first of this species and will serve as a foundation for future genetic and genomic research in support of its management as an agricultural pest.
Self-identification by Sexual and Gender Minorities as a Crucial Aspect of Inclusion in a Study of Adverse Childhood Experiences in Haiti
Authors: Heger Joseph , Paul Phycien , Jean-Baptiste Caleb , Odans Elmondo , Salinas-Miranda Abraham A. , Lynch Erin , Stevens Emily , Rahill Guitele J. , Joshi Manisha
Published: September 2023

Research studies are inevitably affected by contextual norms, local ideologies, social mores, and self-identification in addition to extant policies and laws. Self-identification is often emotionally laden and can be constrained by fear of reprisal if one’s self-identification departs from acceptable and affirmed norms. Such complexities can hinder measurement efforts and results from established measures can fail to yield accurate and thus useful data. Studies of Adverse Childhood Experiences (ACEs) are important but understudied in Haiti. We investigated ACEs in urban Haiti using the ACE International Questionnaire (ACE-IQ). Descriptive statistics revealed: (1) A relationship between participants’ self-identification and sex recorded as observed by interviewers, and (2) Prevalence of ACEs by self-reported identity. Roughly half participants self-identified as ’Woman’ (56%; n = 380), 39% as ’Man’ (n = 265), 2% as ’Homosexual’ (n = 13), and 2% as ’Lesbian’ (n =14). Contradictions emerged between participant self-identification and interviewers’ record of sex: 98% self-identified women were observed/recorded as ’Female’, one was observed/recorded as ’Male’, and there was no record for five. Similarly, 95% self-identified men were observed/recorded as ’Male’, six as ’Female’, two as ’Other’, and there was no record for five. Although Sexual and Gender Minorities (SGM) constituted a small subsample (n = 27), their responses underscored misclassification and disproportionate burdens of physical, emotional, and sexual abuse, family dysfunction, and other forms of interpersonal violence. Conducting ACE-IQ studies in Haiti that provide inclusive categories of self-identification may more equitably capture unique ACEs of all Haitians.
Evaluation of computer vision syndrome in the sample of students from the College of Medicine/University of Kerbala result of online learning with the isolation of COVID-19
Authors: AbuRagheif Mahdy H
Published: September 2023

Background

A complex of vision problems related to stress the vision is experienced during the use of the computer or any digital device. Many of the visual problems that users report is just transient and go away after they stop using computers or other digital devices. Even after stopping their computer job, some people may still have diminished visual abilities, such as blurry distance vision.

Subject and Method

This is a cross-sectional study conducted at the University of Kerbala College of Medicine, which was completed between November 2021 and January 2022, to students of the College of Medicine given student questionnaires about the effects of long-time use of computers, laptops, and mobile phones.

Result

The cross-section studies with questionnaires to 460 students of the College of the Medicine/ University of Karbala, included these studies, we drew lines for the criteria to identify a computer vision syndrome from these associated ocular and extraocular symptoms and recorded a high prevalence of the Computer Vision syndrome reached 91.6%.
The time course of injury-risk after return-to-play in professional football
Authors: Zhang Guangze , Brink Michel , aus der Fünten Karen , Trolß Tobias , Willeit Peter , Meyer Tim , Lemmink Koen , Hecksteden Anne
Published: September 2023

Background

Injury risk in professional football is increased in the weeks following return-to-play (RTP). However, the time course of injury risk after RTP (the hazard curve) as well as its influencing factors are largely unknown. This knowledge gap, which is arguably due to the volatility of instantaneous risk when calculated for short time intervals, impedes on informed RTP decision-making and post-RTP player management.

Objectives

To characterize the hazard curve for non-contact, time-loss injuries after RTP in male professional football and investigate the influence of the severity of the index injury and playing position.

Methods

Media-based injury records from the first German football league were collected over four seasons as previously published. Time-to-event analysis was employed for non-contact, time-loss injury after RTP. The Kaplan-Meier survival function was used to calculate the cumulative hazard function, from which the continuous hazard function was retrieved by derivation.

Results

1623 observed and 1520 censored events from 646 players were analyzed. The overall shape of the hazard curve was compatible with an exponential decline of injury risk, from an approximately two-fold level shortly after RTP towards baseline, with a half-time of about four weeks. Interestingly, the peak of the hazard curve was slightly delayed for moderate and more clearly for severe index injuries.

Conclusions

The time course of injury risk after RTP (the hazard curve) can be characterized based on the Kaplan-Meier model. The shape of the hazard curve and its influencing factors are of practical as well as methodological relevance and warrant further investigation.

Summary box

What is already known on this topic -As football players return to play after an injury, the risk of incurring a subsequent injury is high. With (event-free) time, this elevated risk returns to baseline. However, the shape of the risk-trajectory over time as well as its influencing factors are unknown.

What this study adds -This study characterizes the time course of injury risk after RTP by providing a continuous hazard curve. Moreover, differences in risk trajectories across severities of index injury and playing positions were investigated.How this study might affect research, practice or policy -An evidence-informed estimate of the excess injury risk still remaining at a certain time-point after RTP is of obvious use for RTP decision making and post-RTP player management. Moreover, the continuous hazard curves enable informed specification of follow-up period in epidemiological studies and verification of the proportional hazard assumption in data analysis.
Longitudinal Trajectories of Symptom Change During Antidepressant Treatment Among Managed Care Patients with Co-Occurring Depression and Anxiety
Authors: Cukor Judith , Xu Zhenxing , Vekaria Veer , Wang Fei , Olfson Mark , Banerjee Samprit , Simon Gregory , Alexopoulos George , Pathak Jyotishman
Published: September 2023

Depression and anxiety are highly correlated, yet little is known about the course of each condition when presenting concurrently. This study aimed to identify longitudinal patterns and changes in depression and anxiety symptoms during antidepressant treatment, and evaluate clinical factors associated with each response pattern. Self-report Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7) scores were used to track the courses of depression and anxiety respectively over a three-month window, and group-based trajectory modeling was used to derive subgroups of patients who have similar response patterns. Multinomial regression was used to associate various clinical variables with trajectory subgroup membership. Of the 577 included adults, 373 (64.6%) were women, and the mean age was 39.3 (SD: 12.9) years. Six depression and six anxiety trajectory subgroups were computationally derived; three depression subgroups demonstrated symptom improvement, and three exhibited nonresponse. Similar patterns were observed in the six anxiety subgroups. Factors associated with treatment nonresponse included higher pretreatment depression and anxiety severity and poorer sleep quality, while better overall health and younger age were associated with higher rates of remission. Synchronous and asynchronous paths to improvement were also observed between depression and anxiety. High baseline depression or anxiety severity alone may be an insufficient predictor of treatment nonresponse. These findings have the potential to motivate clinical strategies aimed at treating depression and anxiety simultaneously.
Enhancing HIV testing yield in southern Mozambique: the effect of a Ministry of Health training module in targeted provider-initiated testing and counselling
Authors: Saura-Lázaro Anna , Fernández-Luis Sheila , Nhampossa Tacilta , Fuente-Soro Laura , López-Varela Elisa , Bernardo Edson , Augusto Orvalho , Sánchez Teresa , Vaz Paula , Wei Stanley C. , Kerndt Peter , Honwana Nely , Young Peter , Amane Guita , Boene Fernando , Naniche Denise
Published: September 2023

Background

In Mozambique, targeted provider-initiated HIV testing and counselling (PITC) is recommended to increase HIV testing yield where universal PITC is not feasible. However, its effectiveness depends on healthcare providers’ training. We evaluated the effect of a Ministry of Health training module in targeted PITC on the HIV testing yield.

Methods

We conducted a single-group pre-post study between November 2018 and November 2019 in the triage and emergency departments of four healthcare facilities in Manhiça District. It consisted of two two-month phases split by a one-week targeted PITC training module (“observation phases”). During both phases, providers reported their recommendation to test or not for individuals ≥15 years, and study HIV counsellors performed universal testing. We calculated HIV testing yield of targeted PITC as the proportion of HIV-positive individuals among those provider-recommended and tested. We compared pre- and post-training yields using two-proportion z-test. Additionally, we extracted aggregated health information system data over the four months preceding and following the observation phases to compare yield in real-world conditions (“routine phases”). We used logistic regression to identify predictors of HIV test positivity.

Results

Among 7,102 participants in the pre- and post-training observation phases (58.5% and 41.5% respectively), 68% were women, and 96% were recruited at triage. While HIV testing yield between pre- and post-training observation phases was similar, we observed an increase in yield in the post-training routine phase for women in triage (Yield ratio=1.54; 95%CI: 1.11-2.14). Age (25-49 years) (OR=2.43; 95%CI: 1.37-4.33), working in industry/mining (OR=4.94; 95%CI: 2.17-11.23), unawareness of partner’s HIV status (OR=2.50; 95%CI: 1.91-3.27), and visiting a healer (OR=1.74; 95%CI: 1.03-2.93) were factors associated with HIV test positivity. Including these factors in the targeted PITC algorithm could increase new HIV diagnoses by 2.6%. Furthermore, testing individuals with ≥1 HIV risk factor/symptom and a negative HIV test within the past three months revealed an additional 3.5% of undiagnosed PLHIV.

Conclusions

We found over 50% increase in the HIV testing yield of targeted PITC among women in the four months following the training and observation phases. Including additional sociodemographic and risk factors in the targeted PITC algorithm could help identify undiagnosed PLHIV.
Perivascular space enlargement accelerates with hypertension, white matter hyperintensities, chronic inflammation, and Alzheimer’s disease pathology: evidence from a three-year longitudinal multicentre study
Authors: Menze Inga , Bernal Jose , Kaya Pinar , Aki Çağla , Pfister Malte , Geisendörfer Jonas , Yakupov Renat , Heneka Michael T. , Brosseron Frederic , Schmid Matthias C. , Glanz Wenzel , Incesoy Enise I. , Butryn Michaela , Rostamzadeh Ayda , Meiberth Dix , Peters Oliver , Preis Lukas , Lammerding Dominik , Gref Daria , Priller Josef , Spruth Eike J. , Altenstein Slawek , Lohse Andrea , Hetzer Stefan , Schneider Anja , Fliessbach Klaus , Kimmich Okka , Vogt Ina R. , Wiltfang Jens , Bartels Claudia , Schott Björn H. , Hansen Niels , Dechent Peter , Buerger Katharina , Janowitz Daniel , Perneczky Robert , Rauchmann Boris-Stephan , Teipel Stefan , Kilimann Ingo , Goerss Doreen , Laske Christoph , Munk Matthias H. , Sanzenbacher Carolin , Hinderer Petra , Scheffler Klaus , Spottke Annika , Roy-Kluth Nina , Lüsebrink Falk , Neumann Katja , Jessen Frank , Schreiber Stefanie , Düzel Emrah , Ziegler Gabriel
Published: September 2023

Background

Perivascular space (PVS) enlargement in ageing and Alzheimer’s disease (AD) and its exacerbators require further investigation.

Methods

We studied centrum semiovale (CSO) and basal ganglia (BG) PVS computationally over three to four annual visits in 557 participants of the DZNE multicentre DELCODE cohort. We tested volumetric changes of PVS in relation to ageing, sex, years of education, hypertension, AD diagnosis, and cerebrospinal-fluid-derived Amyloid and Tau positivity and interleukin 6 (IL-6).

Results

PVS volumes increased over time. PVS enlargement was associated with baseline white matter hyperintensities. BG-PVS enlargement was related to age and was faster with hypertension. CSO-PVS volumes increased faster with Amyloid and Tau positivity. Higher CSF IL-6 levels predicted PVS volume expansion in both regions and were associated with accelerated PVS enlargement in individuals with Amyloid and Tau positivity.

Conclusion

Our work supports the region-specific involvement of white matter hyperintensities, neurotoxic waste accumulation, and inflammation in PVS enlargement.
Development and Validation of the Alimetry® Gut-Brain Wellbeing Survey: A novel patient-reported mental health scale for patients with chronic gastroduodenal symptoms
Authors: Law Mikaela , Pickering Isabella , Humphrey Gayl , Sebaratnam Gabrielle , Schamberg Gabriel , Simpson Katie , Varghese Chris , Du Peng , Daker Charlotte , Huang I-Hsuan , Khalsa Sahib S. , Gharibans Armen , O’Grady Greg , Andrews Christopher N. , Calder Stefan
Published: September 2023

Objective

There is currently a lack of validated questionnaires designed specifically to assess mental health within patients with chronic gastroduodenal symptoms. This research describes the multi-phase process used to develop and validate a novel mental health scale for patients with chronic gastroduodenal symptoms, the Alimetry® Gut-Brain Wellbeing (AGBW) Survey.

Methods

A patient-centred multi-phase process was implemented. In Phase 1, the most relevant concepts for this patient population were selected from existing mental health scales, using data from 79 patients. In Phase 2, an interdisciplinary panel of experts generated scale items. In Phase 3, the scale underwent pre-testing with gastroenterologists (n=9), health psychologists (n=3), and patients (n=12), with feedback incorporated over multiple rounds. Lastly, the psychometric properties of the scale were assessed in a sample of 311 patients via an online survey.

Results

The AGBW Survey comprises a patient preface, 10 close-ended questions, and an optional open-ended question. This multidimensional scale assesses general mental health, alongside specific subscales relating to depression, stress, and anxiety. The subscale and total scores demonstrated high internal consistency (α= .91 for the total scale; α= .72-.86 for subscales) and good convergent, divergent, concurrent validity, and known groups validity, with large effect sizes.

Conclusions

The AGBW Survey is a brief, valid, and reliable scale for assessing mental health in patients with chronic gastroduodenal symptoms. It can be used as a tool to complement physiological tests and has the potential to guide psychological referrals, inform multidisciplinary management, and evaluate treatment outcomes.
Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort
Authors: Tribin Felipe Echeverri , Williams Erin , Testamarck Valeska , Carreño Juan Manuel , Bielak Dominika , Yellin Temima , Krammer Florian , Hoffer Michael , Pallikkuth Suresh , Pahwa Savita
Published: September 2023

Post vaccine immunity following COVID-19 mRNA vaccination may be driven by extrinsic, or controllable and intrinsic, or inherent health factors. Thus, we investigated the effects of extrinsic and intrinsic on the peak antibody response following COVID-19 primary vaccination and on the trajectory of peak antibody magnitude and durability over time. Participants in a longitudinal cohort attended visits every 3 months for up to 2 years following enrollment. At baseline, participants provided information on their demographics, recreational behaviors, and comorbid health conditions which guided our model selection process. Blood samples were collected for serum processing and spike antibody testing at each visit. Cross-sectional and longitudinal models (linear-mixed effects models) were generated to assess the relationship between selected intrinsic and extrinsic health factors on peak antibody following vaccination and to determine the influence of these predictors on antibody over time. Following cross-sectional analysis, we observed higher peak antibody titers after primary vaccination in females, those who reported recreational drug use, younger age, and prior COVID-19 history. Following booster vaccination, females and Hispanics had higher peak titers after the 3rdand 4thdoses, respectively. Longitudinal models demonstrated that Moderna mRNA-1273 recipients, females, and those previously vaccinated had increased peak titers over time. Moreover, drug users and half-dose Moderna mRNA-1273 recipients had higher peak antibody titers over time following the first booster, while no predictive factors significantly affected post-second booster antibody responses. Overall, both intrinsic and extrinsic health factors play a significant role in shaping humoral immunogenicity after initial vaccination and the first booster. The absence of predictive factors for second booster immunogenicity suggests a more robust and consistent immune response after the second booster vaccine administration.
Activation induces shift in nutrient utilization that differentially impacts cell functions in human neutrophils
Authors: Britt Emily C. , Qing Xin , Votava James A. , Lika Jorgo , Wagner Andrew , Shen Simone , Arp Nicholas L. , Khan Hamidullah , Schieke Stefan M. , Fletcher Christopher D. , Huttenlocher Anna , Fan Jing
Published: September 2023

Neutrophils – the first responders in innate immunity – perform a variety of effector functions associated with specific metabolic demand. To maintain fitness and support functions, neutrophils have been found to utilize extracellular glucose, intracellular glycogen, and other alternative substrates. However, the quantitative contribution of these nutrients under specific conditions and the relative dependence of various cell functions on specific nutrients remain unclear. Here, usingex vivoandin vivoisotopic tracing, we reveal that under resting condition, human peripheral blood neutrophils, in contrast toin vitrocultured human neutrophil-like cell lines, rely on glycogen as a major direct source of glycolysis and pentose phosphate pathway. Upon activation with a diversity of stimuli, neutrophils undergo a significant and often rapid nutrient preference shift, with glucose becoming the dominant metabolic source thanks to a multi-fold increase in glucose uptake mechanistically mediated by the phosphorylation and translocation of GLUT1. At the same time, cycling between gross glycogenesis and glycogenolysis is also substantially increased, while the net flux favors sustained or increased glycogen storage. The shift in nutrient utilization impacts neutrophil functions in a function-specific manner. The activation of oxidative burst specifically depends on the utilization of extracellular glucose rather than glycogen. In contrast, the release of neutrophil traps can be flexibly supported by either glucose or glycogen. Neutrophil migration and fungal control is promoted by the shift away from glycogen utilization. Together, these results quantitatively characterize fundamental features of neutrophil metabolism and elucidate how metabolic remodeling shapes neutrophil functions upon activation.
Alpha-synuclein expression in neuron modulates the Japanese encephalitis virus infection
Authors: Gupta Anjali , Mohapatra Anshuman , Kaur Harpreet , Sharma Ajanta , Chaudhary Nitin , Kumar Sachin
Published: September 2023

Japanese encephalitis virus (JEV) stands as a prominent vector-borne zoonotic pathogen, displaying neurotropism and eliciting Parkinson’s disease (PD)-like symptoms among most symptomatic survivors. A characteristic feature of PD is aggregation of mutated α-synuclein (α-syn) that damages the dopaminergic neurons. Considering this link between JEV-induced PD-like symptoms and α-syn pathogenesis, we explored the role of α-syn in JEV infectivity in neuronal cells. Our investigation revealed significant increase in endogenous α-syn expression in JEV-infected cells. Additionally, treatment with exogenous α-syn (Exoα-syn) led to a substantial reduction in JEV replication, suggesting its anti-JEV effect. Furthermore, Exoα-syn treatment led to the upregulation of superoxide dismutase 1 (SOD1) and reduction in reactive oxygen species (ROS). The results were validated by endogenous α-syn-silencing, that decreased SOD1 level and raised ROS level in neuronal cells. Similarly, the SOD1 inhibition via LCS-1 also intensified ROS and JEV infection. Overall, our results suggest that α-syn exerts an anti-JEV effect by regulating protein involved in oxidative stress inside neuronal cells. This study contributes valuable insights into the interplay between α-syn expression and JEV infectivity, shedding light on avenues to further investigate the potential role of α-syn in JEV pathogenesis.

Importance

Japanese encephalitis virus (JEV) poses significant threat particularly to children. Despite extensive research efforts, the development of effective treatments against JEV has been impeded. One of the major setbacks is a lack of comprehensive understanding of neurotropism. The study focuses on alpha synuclein (α-syn), a neuronal protein, and aims to determine its role in JEV pathogenesis. Present study reveals that host cell upregulates α-syn in response of JEV infection. α-syn restrains JEV propagation by modulating superoxide dismutase 1 (SOD1) expression which further blocks JEV-induced ROS generation. Endogenous α-syn silencing led to decrease in SOD1 expression and increased viral titer. α-syn plays crucial role in counteracting oxidative stress through SOD1, which is essential for limiting JEV replication. This study provides broader implications for antiviral strategies and its possible role in neurodegenerative diseases; however, there is still much to explore, particularly regarding its aggregation kinetics in JEV infection.
Genomic surveillance ofClostridioides difficiletransmission and virulence in a healthcare setting
Authors: Newcomer Erin P. , Fishbein Skye R. S. , Zhang Kailun , Hink Tiffany , Reske Kimberly A. , Cass Candice , Iqbal Zainab H. , Struttmann Emily L. , Dubberke Erik R. , Dantas Gautam
Published: September 2023

Clostridioides difficileinfection (CDI) is a major cause of healthcare-associated diarrhea, despite the widespread implementation of contact precautions for patients with CDI. Here, we investigate strain contamination in a hospital setting and genomic determinants of disease outcomes. Across two wards over six months, we selectively culturedC. difficilefrom patients (n=384) and their environments. Whole-genome sequencing (WGS) of 146 isolates revealed that mostC. difficileisolates were from clade 1 (131/146, 89.7%), while only one isolate of the hypervirulent ST1 was recovered. Of culture-positive admissions (n=79), 19 (24%) of patients were colonized with toxigenicC. difficileon admission to the hospital. We defined 25 strain networks at ≤ 2 core gene SNPs; 2 of these networks contain strains from different patients. Strain networks were temporally linked (p<0.0001). To understand genomic correlates of disease, we conducted WGS on an additional cohort ofC. difficile(n=102 isolates) from the same hospital and confirmed that clade 1 isolates are responsible for most CDI cases. We found that while toxigenicC. difficileisolates are associated with the presence ofcdtR, nontoxigenic isolates have an increased abundance of prophages. Our pangenomic analysis of clade 1 isolates suggests that while toxin genes (tcdABER and cdtR) were associated with CDI symptoms, they are dispensable for patient colonization. These data indicate toxigenic and nontoxigenicC. difficilecontamination persists in a hospital setting and highlight further investigation into how accessory genomic repertoires contribute toC. difficilecolonization and disease.
An unsupervised machine learning approach to predict recovery from traumatic spinal cord injury
Authors: Brüningk Sarah C. , Bourguignon Lucie , Lukas Louis P. ,   EMSCI study group, Maier Doris , Abel Rainer , Weidner Norbert , Rupp Rüdiger , Geisler Fred , Kramer John L.K. , Guest James , Curt Armin , Jutzeler Catherine R.
Published: September 2023

Background

Neurological and functional recovery after traumatic spinal cord injury (SCI) is highly heterogeneous, challenging outcome predictions in rehabilitation and clinical trials. We propose k-nearest neighbour (k-NN) matching as a data-driven, interpretable solution.

Methods

This study used acute-phase International Standards for Neurological Classification of SCI exams to forecast 6-month recovery motor function as primary evaluation endpoint. Secondary endpoints included severity grade improvement, independent walking, and self-care ability. Different similarity metrics were explored for NN matching within 1267 patients from the European Multicenter Study about Spinal Cord Injury before validation in 411 patients from the Sygen trial.

Results

We obtained a population-wide root-mean-squared error (RMSE) in motor score sequence of 0.76(0.14, 2.77) and competitive functional score predictions (AUCwalker=0.92, AUCself-carer=0.83). The validation cohort showed comparable results (RMSE = 0.75(0.13, 2.57), AUCwalker=0.92). Prediction performance in AIS grade B and C patients (∼30%) showed the largest deviations from true recovery scores, in line with large SCI heterogeneity.

Conclusions

Our approach provides detailed predictions of neurological and functional recovery based on a highly interpretable unsupervised machine learning concept. The k-NN matching strategy further enables the integration of historical control data into the evaluation of clinical trials and provides a data-driven digital twin for recovery trajectory exploration.
Immunologic predictors of vaccine responsiveness in patients with lymphoma and CLL
Authors: Chong Elise A. , Kumashie Kingsley Gideon , Chong Emeline R. , Fabrizio Joseph , Gupta Aditi , Svoboda Jakub , Barta Stefan K. , Walsh Kristy M. , Napier Ellen B. , Lundberg Rachel K. , Nasta Sunita D. , Gerson James N. , Landsburg Daniel J. , Gonzalez Joyce , Gaano Andrew , Weirick Madison E. , McAllister Christopher M. , Awofolaju Moses , John Gavin N. , Kammerman Shane C. , Novaceck Josef , Pajarillo Raymone , Lundgreen Kendall A. , Tanenbaum Nicole , Gouma Sigrid , Drapeau Elizabeth M. , Adamski Sharon , D’Andrea Kurt , Pattekar Ajinkya , Hicks Amanda , Korte Scott , Sharma Harsh , Herring Sarah , Williams Justine C. , Hamilton Jacob T. , Bates Paul , Hensley Scott E. , Luning Prak Eline T. , Greenplate Allison R. , Wherry E. John , Schuster Stephen J. , Ruella Marco , Vella Laura A.
Published: September 2023

Patients with B-cell lymphomas have altered cellular components of vaccine responses due to the malignancies and therapies. The optimal timing of vaccine administration relative to chemotherapy and immunotherapy remains unknown. The SARS-CoV-2 vaccine campaign created a unique opportunity to gather insights into vaccine timing because patients were challenged with a novel antigen across multiple phases of lymphoma management. We studied retrospective and prospective cohorts of patients with lymphoma and CLL who received an mRNA-based vaccine and paired serologic response with treatment dates, clinical immune parameters, and deep immunophenotyping. Reduced serologic response was observed more frequently during active therapies but nonresponders were also identified within observation and post-treatment groups. Clinical immunologic profiling demonstrated that total IgA and IgM near the time of vaccination correlated with ability to coordinate vaccine response. In individuals treated with CART-19, high-parameter immunophenotyping demonstrated that nonresponse was associated with reduced participation in B cell clusters and clusters of T follicular helper cells required for vaccine response. Together these data suggest that predictors of vaccine responsiveness vary by disease and therapeutic group. Further studies of immune health during and after cancer therapies will allow clinicians to individualize the timing of vaccines and define immunologic vulnerabilities.
Genomic Insights into Pediatric Intestinal Inflammatory and Eosinophilic Disorders using Single-sell RNA-sequencing
Authors: Keever-Keigher Marissa R. , Harvey Lisa , Williams Veronica , Vyhlidal Carrie A. , Ahmed Atif A. , Johnston Jeffery J. , Louiselle Daniel A. , Grundberg Elin , Pastinen Tomi , Friesen Craig A. , Chevalier Rachel , Smail Craig , Shakhnovich Valentina
Published: September 2023

Chronic inflammation of the gastrointestinal tissues underlies gastrointestinal inflammatory disorders, leading to tissue damage and a constellation of painful and debilitating symptoms. These disorders include inflammatory bowel diseases (Crohn’s disease and ulcerative colitis), and eosinophilic disorders (eosinophilic esophagitis and eosinophilic duodenitis). Gastrointestinal inflammatory disorders can often present with overlapping symptoms necessitating the use of invasive procedures to give an accurate diagnosis. This study used peripheral blood mononuclear cells from individuals with Crohn’s disease, ulcerative colitis, eosinophilic esophagitis, and eosinophilic duodenitis to better understand the alterations to the transcriptome of individuals with these diseases and identify potential markers of active inflammation within the peripheral blood of patients that may be useful in diagnosis. Single-cell RNA-sequencing was performed on peripheral blood mononuclear cells isolated from the blood samples of pediatric patients diagnosed with gastrointestinal disorders, including Crohn’s disease, ulcerative colitis, eosinophilic esophagitis, eosinophilic duodenitis, and controls with histologically healthy gastrointestinal tracts. We identified 730 (FDR < 0.05) differentially expressed genes between individuals with gastrointestinal disorders and controls across eight immune cell types. There were common patterns among GI disorders, such as the widespread upregulation ofMTRNR2L8across cell types, and many differentially expressed genes showed distinct patterns of dysregulation among the different gastrointestinal diseases compared to controls, including upregulation ofXISTacross cell types among individuals with ulcerative colitis and upregulation of Th2-associated genes in eosinophilic disorders. These findings indicate both overlapping and distinct alterations to the transcriptome of individuals with gastrointestinal disorders compared to controls, which provide insight as to which genes may be useful as markers for disease in the peripheral blood of patients.
Analysis of Potential Risk Factors of COVID-19 Based on Variants: Omicron, Delta, and Alpha
Authors: Kannan Dharshini , Muppiri Sreenidhi , Reid Maren
Published: September 2023

The coronavirus disease 2019 (COVID-19) pandemic has changed which affects the risk of COVID-19 infection for specific subgroups. We focused on the subgroups based on the factors (sex, age, and vaccination) and COVID-19 strains (Alpha, Delta, and Omicron). Past studies focused on analyzing these factors based on one geographic region or one COVID-19 strain. Therefore, there is a need to understand these factors’ association with risk of COVID-19 infection through analyzing data from various geographic regions and strains. The association between COVID-19 strains and the factors was assessed through chi-square test and odds ratio tests. Sex, vaccination, age had a significant association with testing positive for the COVID-19 strains of interest in most geographies. The biggest difference was unvaccinated individuals have 3.14 higher odds of getting Alpha than vaccinated individuals in Canada. These findings provide insights into the groups that are more susceptible to contracting specific strains of COVID-19.

This manuscript offers a broad examination of key factors that may impact the risk of COVID-19 infection across various geographic regions. Results provide evidence about potential risk factors for COVID-19 infection around the world for certain sub-groups as COVID-19 mutates.