bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolated diastolic hypertension in childhood and risk of adult subclinical target organ damage: a 30-year prospective cohort study
Authors: Liao Yueyuan , Chu Chao , Wang Yang , Zheng Wenling , Ma Qiong , Hu Jiawen , Yan Yu , Yang Jun , Yang Ruihai , Wang Keke , Yuan Yue , Chen Chen , Sun Yue , Mu Jianjun
Published: June 2022

Background:

Data on the association of isolated diastolic hypertension (IDH) in childhood with adult cardiovascular risk are scarce. This study aimed to estimate the prevalence of IDH in adolescents and to explore the impact of IDH in childhood on adult subclinical target organ damage (STOD).

Methods:

This longitudinal study consisted of 1738 school children (55.4% boys) aged 6–15 years from rural areas of Hanzhong, Shaanxi, who were followed for 30 years. Their blood pressure was recorded to define the hypertension subtypes: normotension, IDH, isolated systolic hypertension (ISH) and mixed hypertension. Tracked STOD included arterial stiffness (n = 1738), albuminuria (n = 1652) and left ventricular hypertrophy (LVH) (n = 1429).

Results:

Overall, the prevalence of IDH, ISH and mixed hypertension was 5.4, 2.2 and 3%, respectively, and there was no gender difference. Over 30 years, 366 (21.1%) of participants developed arterial stiffness, 170 (10.3%) developed albuminuria and 68 (4.8%) developed LVH. Compared with normotensive participants, IDH in childhood had higher risk ratio (RR) of experiencing arterial stiffness (RR, 1.66; 95% CI, 1.01–2.76) and albuminuria (RR, 2.27; 95% CI, 1.35–4.16) in adults after being fully adjusted but not LVH. However, if the elevated blood pressure in children was used as the reference standard, IDH in childhood was associated with adult LVH (RR, 2.48; 95% CI, 1.28–4.84).

Conclusion:

IDH accounts for a higher proportion of adolescent hypertension subtypes and can increase the risk of adult STOD. These results highlight the necessity of improving the prevention, detection and treatment of IDH in adolescents.
Drug-Associated Liver Injury Related to Antipsychotics
Authors: Zeiss René , Hafner Susanne , Schönfeldt-Lecuona Carlos , Connemann Bernhard J. , Gahr Maximilian
Published: June 2022

Background

Drug-associated liver injury is one of the most common causes for acute liver failure and market withdrawal of approved drugs. In addition, the potential for hepatotoxicity related to specific substances has to be considered in psychopharmacotherapy. However, systematic evaluations of hepatotoxicity related to antipsychotics are limited.

Methods

We conducted an exploratory case/non-case study and evaluated pharmacovigilance data from VigiBase related to 30 antipsychotics marketed in the European Union. Reporting odds ratios were calculated for antipsychotics associated with the Standardized Medical Dictionary of Regulatory Activities queries “Drug-related hepatic disorders–comprehensive search” (DRHD-CS) and “Drug-related hepatic disorders–severe events only” (DRHD-SEO).

Results

We found several signals for drug-associated liver injury including signals for severe events: 17 of 30 antipsychotics were associated with DRHD-CS and 10 of 30 antipsychotics with DRHD-SEO. Amisulpride, fluphenazine, levomepromazine, loxapine, olanzapine, perazine, perphenazine, pipamperone, sulpiride, and thioridazine were associated with both, DRHD-CS and DRHD-SEO. No association with fatal outcomes was detected.

Conclusions

Several common antipsychotics are associated with hepatotoxicity, partly also with severe hepatotoxicity. Our data do not allow to account for patient-related risk factors for drug-associated liver injury. This should be addressed in further studies.
“Keep It to Yourself”: A Qualitative Study of HIV Disclosure Perspectives Among Older Adults Living With HIV in South Carolina Who Are Childhood Sexual Abuse Survivors
Authors: Brown Monique J. , Nkwonta Chigozie A. , James Titilayo , Kaur Amandeep , Hart Mackenzie J. , Addo Prince Nii Ossah , Adeagbo Oluwafemi A.
Published: June 2022

HIV disclosure is an important consideration for people living with HIV. The prevalence of childhood sexual abuse (CSA) may range from 16% to 22% among older adults living with HIV. There is a dearth of research on HIV disclosure among older CSA survivors. Therefore, the aim of this study was to qualitatively examine HIV disclosure among older CSA survivors living with HIV. Twenty-four CSA survivors living with HIV (aged 50–67 years) participated in in-depth, semistructured interviews. Data were analyzed thematically, and the iterative coding and analytic process included discussion of initial thoughts and key concepts, identification and reconciliation of codes, and naming of emergent themes. Four themes emerged: (a) secrecy/not planning to disclose HIV; (b) disclose HIV regardless; (c) disclose HIV depending on the person; and (d) disclose HIV depending on the circumstance. Lack of disclosure may be due to HIV-related stigma. HIV disclosure intervention programs may be beneficial for this population
Association Between the Metabolic Syndrome and Retinal Microvascular Diameters Among Police Officers
Authors: Gu Ja K. , Charles Luenda E. , Allison Penelope , Violanti John M. , Andrew Michael E.
Published: June 2022

Objectives

We examined the associations of the metabolic syndrome severity score (MSSS) and the metabolic syndrome (MetSyn) components with central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE).

Methods

Participants in this cross-sectional study were 253 officers from the Buffalo Cardio-Metabolic Occupational Police Stress study (2011–2014). The MSSS is a z-score that represents the severity of MetSyn and was estimated using a sex/race-specific equation and the five MetSyn components. Associations of MSSS and the MetSyn with CRAE/CRVE were obtained using linear regression models or analysis of covariance.

Results

For every 1-standard deviation of MSSS, CRAE decreased by 2.3 μm (SE = 1.2, P = 0.0262) and CRVE increased by 3.4 μm (SE = 1.6, P = 0.0308) after adjusting for confounders.

Conclusions

Officers with higher MSSS had narrower (ie, worse) arteriolar diameters and wider (ie, worse) venular diameters.
Variants of uncertain significance in the era of next-generation sequencing
Authors: Levkova Mariya , Stoyanova Milena , Benkova-Petrova Miroslava , Georgieva Miglena , Angelova Lyudmila
Published: June 2022

Next-generation sequencing (NGS) is now widely used in diagnosing rare diseases. However, it has some limitations, such as variants of uncertain significance (VUS). This can present difficulties even for nurse practitioners involved in clinical genetics. We present three cases from our clinical practice: two targeted panel testing and one exome sequencing. Whole blood samples were collected and sent for NGS analysis. In case 1, a VUS was found in the LITAF gene, which is associated with autosomal dominant Charcot–Marie–Tooth disease type 1C. In case 2, a VUS was reported in the MEFV gene, which is associated with autosomal recessive and autosomal dominant familial Mediterranean fever. In these cases, the reported VUS corresponded to the clinical diagnosis. In case 3, two variants in the heterozygous state were found in the ATP7B gene, which is associated with Wilson disease, and the disorder was later clinically recognized. According to the published guidelines, VUSs should not be discussed as a cause for an observed genetic condition. Nevertheless, if the reported variant is in a gene associated with the clinically diagnosed disorder, and there is a strong genotype-phenotype correlation, it could be suggestive of the etiological role of this variant.
Solifenacin Treatment After Intradetrusor Injections With Botulinum Toxin in Patients With Neurogenic Detrusor Overactivity
Authors: Ciofu Irina , Ceausu Iuliana , Chirca Narcis Marian , Persu Cristian
Published: June 2022

Background:

Neurogenic detrusor overactivity (NDO) is treated with antimuscarinics as first-line treatment. For patients with contraindications or unresponsive, intradetrusor injections with botulinum toxin (BoNT) are a safe and effective but expensive option.

Study Question:

Our study evaluated whether adding solifenacin to the intradetrusor injection of BoNT A could boost the effect of BoNT in patients with NDO due to multiple sclerosis or spinal cord injury refractory to antimuscarinics alone and/or lead to less frequent injections.

Study Design:

We performed a prospective study on 49 patients assigned alternatively to group A, undergoing BoNT injections, and group B, adding solifenacin.

Measures and Outcomes:

We gathered data from urodynamic testing and questionnaire assessments before and 3 months after injections and reinjections. We analyzed 39 patients who achieved total continence and a minimum 24-month follow-up period.

Results:

After treatment, both groups had statistically significant improvement of overactive bladder questionnaire (OABq) score, post void residue (PVR), and peak detrusor pressure (Pdet). Reinjection was needed after a mean 8.2 months for group A and 11.7 months for group B. We analyzed the improvement rate of parameters compared between the 2 groups—group B had greater OABq score improvement (A = 17.25 ± 5.07, B = 20.44 ± 4.51, P = 0.0485), as well as for maximum bladder capacity (A = 11.05 ± 7.04 mL, B = 19.39 ± 6.43 mL, P = 0.0005); differences in Pdet change (A = 51.72 ± 16.57 cmH2O, B = 50.80 ± 16.33 cmH2O, P = 0.7635) and PVR change (A = 17.67 ± 12.63 mL, B = 12.30 ± 8.32 mL, P = 0.126) were not statistically significant.

Conclusions:

Our study shows that adding solifenacin improves patient satisfaction, increases the interval between reinjections, thus lowering costs, and improves maximum bladder capacity. Pdet was kept in safe ranges, but no statistically significant conclusions could be drawn regarding Pdet and PVR decrease related to adding solifenacin. Although our study is limited by the small series of patients and lack of randomization and placebo control group, the BoNT–solifenacin combination could be considered in NDO in terms of cost-effectiveness. Further studies would be beneficial.
Rehabilitation for COVID-19 in conjunction with early awake extracorporeal membrane oxygenation support: a case report
Authors: Han Yuji , Jeong Han Soo , Shim Hunbo , Jung Choi Hee , Yun Bae Ji , Suh Jee Hyun
Published: June 2022

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 can lead to acute respiratory distress syndrome. Awake venovenous extracorporeal membrane oxygenation is known to be effective in patients with critical COVID-19 and respiratory failure. This report describes the rehabilitation course and functional progress of a 63-year-old man who contracted severe COVID-19 and underwent awake venovenous extracorporeal membrane oxygenation. He started rehabilitation from the time of isolation while receiving venovenous extracorporeal membrane oxygenation and underwent a 30-day course of inpatient comprehensive rehabilitation. He regained functional independence and cognitive abilities and was able to walk without assistance at hospital discharge without any complications. This study demonstrates the feasibility of starting rehabilitation for COVID-19 early while the patient is on awake venovenous extracorporeal membrane oxygenation and eventually achieving a favorable outcome.
Long-lasting adaptive immune memory specific to SARS-CoV-2 in convalescent coronavirus disease 2019 stable people with HIV
Authors: Donadeu Laura , Tiraboschi Juan Manuel , Scévola Sofía , Torija Alba , Meneghini Maria , Jouve Thomas , Favà Alexandre , Calatayud Laura , Ardanuy Carmen , Cidraque Ignacio , Preyer Rosemarie , Strecker Kevin , Lozano Juan J. , Podzamczer Daniel , Crespo Elena , Bestard Oriol
Published: June 2022

Objective:

While the course of natural immunization specific to SARS-CoV-2 has been described among convalescent coronavirus disease 2019 (COVID-19) people without HIV (PWOH), a thorough evaluation of long-term serological and functional T- and B-cell immune memory among people with HIV (PWH) has not been reported.

Methods:

Eleven stable PWH developing mild (n = 5) and severe (n = 6) COVID-19 and 39 matched PWOH individuals with mild (MILD) (n = 20) and severe (SEV) (n = 19) COVID-19 infection were assessed and compared at 3 and 6 months after infection for SARS-CoV-2-specific serology, polyfunctional cytokine (interferon-γ [IFN-γ], interleukin 2 [IL-2], IFN-γ/IL-2, IL-21) producing T-cell frequencies against four main immunogenic antigens and for circulating SARS-CoV-2-specific immunoglobulin G (IgG)-producing memory B-cell (mBc).

Results:

In all time points, all SARS-COV-2-specific adaptive immune responses were highly driven by the clinical severity of COVID-19 infection, irrespective of HIV disease. Notably, while a higher proportion of mild PWH showed a higher decay on serological detection between the two time points as compared to PWOH, persistently detectable IgG-producing mBc were still detectable in most patients (4/4 (100%) for SEV PWH, 4/5 (80%) for MILD PWH, 10/13 (76.92%) for SEV PWOH and 15/18 (83.33%) for MILD PWOH). Likewise, SARS-CoV-2-specific IFN-γ-producing T-cell frequencies were detected in both PWH and PWOH, although significantly more pronounced among severe COVID-19 (6/6 (100%) for SEV PWH, 3/5 (60%) for MILD PWH, 18/19 (94.74%) for SEV PWOH and 14/19 (73.68%) for MILD PWOH).

Conclusions:

PWH develop a comparable short and long-term natural functional cellular and humoral immune response than PWOH convalescent patients, which are highly influenced by the clinical severity of the COVID-19 infection.
Clonal hematopoiesis in men living with HIV and association with subclinical atherosclerosis
Authors: Wang Shiyu , Pasca Sergiu , Post Wendy S. , Langan Susan , Pallavajjalla Aparna , Haley Lisa , Gocke Christopher , Budoff Matthew , Haberlen Sabina , Brown Todd T. , Ambinder Richard F. , Margolick Joseph B. , Gondek Lukasz P.
Published: June 2022

Objectives:

People living with HIV (PLWH) are at increased risk for premature cardiovascular disease (CVD). Clonal hematopoiesis (CH) is a common age-related condition that may be associated with increased CVD risk. The goal of this study was to determine the prevalence of CH and its association with chronic inflammation and CVD in PLWH.

Design:

Cross-sectional study utilizing archived specimens and data from 118 men (86 PLWH and 32 HIV-uninfected) from the Baltimore-Washington DC center of the Multicenter AIDS Cohort Study (MACS) who had had coronary computed tomography angiography (CTA) and measurement of 34 serologic inflammatory biomarkers.

Methods:

CH was assessed on peripheral blood mononuclear cells utilizing targeted error-corrected next generation sequencing (NGS) focused on 92 genes frequently mutated in hematologic malignancies. Clinical and laboratory data were obtained from the MACS database.

Results:

CH with a variant allele frequency (VAF) >1% was significantly more common in PLWH [20/86 (23.3%)] than in HIV-uninfected men [2/32 (6.3%)] (p = 0.035). PLWH with CH (VAF>1%) were more likely to have coronary artery stenosis ≥ 50% than those without CH (6/20 (30%) vs. 6/64 (9%); p = 0.021). Presence of CH was not significantly associated with serological inflammatory markers, except for significantly lower serum leptin levels; this was not significant after adjustment for abdominal or thigh subcutaneous fat area.

Conclusions:

CH was more common in PLWH and among PLWH was associated with the extent of coronary artery disease. Larger studies are needed to further examine the biological and clinical consequences of CH in PLWH.
Exploratory study of an oral screening dysplasia program for HIV-infected men who have sex with men
Authors: Callejo Angela , Molina Maria del Mar , Dinares Maria Carme , Hernández-Losa Javier , Planas Bibiana , Garcia Jorge , Curran Adria , Navarro Jordi , Suanzes Paula , Falcó Vicenç , Burgos Joaquin
Published: June 2022

Background:

HIV-infected men who have sex with men (MSM) are at high risk to develop human papilloma virus (HPV)-related oropharyngeal cancer. The aim of our study was to assess the usefulness of a pilot oral dysplasia screening program and its correlation with an anal dysplasia screening program.

Methods:

This was a prospective study with HIV-infected MSM. Oral and anal screenings were performed based on HPV determination, liquid cytology, direct and microscopy oral examinations, high-resolution anoscopy and biopsies, if necessary.

Results:

A total of 103 patients were included. The mean age of the patients was 44.6 years, 55.3% were smokers, and 57.3% had a history of previous anal high-grade squamous intraepithelial lesions (HSILs).

The prevalence of oral HPV infections was 14% (9% HPV-high risk), the prevalence of abnormal cytology was 25.2%, and in 4.8% of the patients, oral examinations showed suspicious HSILs. Oral microscopy did not detect additional lesions that visual inspection. Five oral biopsies were performed and the results were normal. No risk factors for oral HPV infections were identified.

The prevalence of anal HPV infections was 88.3% (76.7% HPV-high risk), 52.9% of the patients had altered cytology, and in 45.6% anoscopy showed changes suggestive of HSILs. Seventy-two anal biopsies were performed, detecting 25 cases of HSILs (24.3%).

A poor correlation was observed between oral and anal HPV infections (κ = 0.037).

Conclusions:

The prevalence of oral HPV infections, abnormal cytology and lesions in HIV-infected MSM was low, and their correlation with anal HPV-related lesions was slight. These results confirm the current barriers to oral dysplasia screening techniques.
A role for CD4+ helper cells in HIV control and progression
Authors: Rouzine Igor M.
Published: June 2022

Objective:

It remains unclear why HIV persists in most untreated individuals, and why a small minority of individuals can control the virus, either spontaneously or after an early treatment. Striking differences have been discovered between patient cohorts in CD4+ T-cell avidity but not in CD8+ T-cell avidity. The present work has the aim to explain the diverse outcome of infection and identify the key virological and immunological parameters predicting the outcome.

Design and method:

A mathematical model informed by these experiments and taking into account the details of HIV virology is developed.

Results:

The model predicts an arms race between viral dissemination and the proliferation of HIV-specific CD4+ helper cells leading to one of two states: a low-viremia state (controller) or a high-viremia state (progressor). Helper CD4+ cells with a higher avidity favor virus control. The parameter segregating spontaneous and posttreatment controllers is the infectivity difference between activated and resting CD4+ T cells. The model is shown to have a better connection to experiment than a previous model based on T-cell ‘exhaustion’.

Conclusion:

Using the model informed by patient data, the timing of antiretroviral therapy can be optimized.
No evidence that circulating HIV-specific immune responses contribute to persistent inflammation and immune activation in persons on long-term ART
Authors: Ward Adam R. , Thomas Allison S. , Stevenson Eva M. , Huang Szu-Han , Keating Sheila M. , Gandhi Rajesh T. , McMahon Deborah K. , Bosch Ronald J. , Macatangay Bernard J. , Cyktor Joshua C. , Eron Joseph J. , Mellors John W. , Jones R. Brad
Published: June 2022

Objective:

People with HIV (PWH) have persistently elevated levels of inflammation and immune activation despite suppressive antiretroviral therapy (ART), with specific biomarkers showing associations with non-AIDS-defining morbidities and mortality. We investigated the potential role of the HIV-specific adaptive immune response, which also persists under ART, in driving levels of these clinically relevant biomarkers.

Design:

Cohort-based study.

Methods:

HIV-specific IFN-γ-producing T-cell responses and antibody concentrations were measured in blood at study entry in the ACTG A5321 cohort, following a median of 7 years of suppressive ART. HIV persistence measures including cell-associated (CA)-DNA, CA-RNA, and plasma HIV RNA (single-copy assay) were also assessed at study entry. Plasma inflammatory biomarkers and T-cell activation and cycling were measured at a pre-ART time point and at study entry.

Results:

Neither the magnitudes of HIV-specific T-cell responses nor HIV antibody levels were correlated with levels of the inflammatory or immune activation biomarkers, including hs-CRP, IL-6, neopterin, sCD14, sCD163, TNF-α, %CD38+HLA-DR+ CD8+ and CD4+ cells, and %Ki67+ CD8+ and CD4+ cells – including after adjustment for pre-ART biomarker level. Plasma HIV RNA levels were modestly correlated with CD8+ T-cell activation (r = 0.25, P = 0.027), but other HIV persistence parameters were not associated with these biomarkers. In mediation analysis, relationships between HIV persistence parameters and inflammatory biomarkers were not influenced by either HIV-specific T-cell responses or antibody levels.

Conclusion:

Adaptive HIV-specific immune responses do not appear to contribute to the elevated inflammatory and immune activation profile in persons on long-term ART.
The transition between acute and chronic infections in light of energy control: a mathematical model of energy flow in response to infection
Authors: Zhao Gang , Straub Rainer H. , Meyer-Hermann Michael
Published: June 2022

Background: Different parts of an organism like the gut, endocrine, nervous and immune systems constantly exchange information. Understanding the pathogenesis of various systemic chronic diseases increasingly relies on understanding how these subsystems orchestrate their activities. Methods: We started from the working hypothesis that energy is a fundamental quantity that governs activity levels of all subsystems and that interactions between subsystems control the distribution of energy according to acute needs. Based on physiological knowledge, we constructed a mathematical model for the energy flow between subsystems and analysed the resulting organismal responses to
in silico
infections. Results: The model reproduces common behaviour in acute infections and suggests several host parameters that modulate infection duration and therapeutic responsiveness. Moreover, the model allows the formulation of conditions for the induction of chronic infections and predicts that alterations in energy released from fat can lead to the transition from clearance of acute infections to a chronic inflammatory state. Impact: These results suggest a fundamental role for brain and fat in controlling immune response through systemic energy control. In particular, it suggests that lipolysis resistance, which is known to be involved in obesity and ageing, might be a survival programme for coping with chronic infections.
Cost–benefit considerations have limited effect on the decision to exert cognitive effort in real-world computer-programming tasks
Authors: Lachman Itamar , Hadar Irit , Hertz Uri
Published: June 2022

Recent research shows that people usually try to avoid exerting cognitive effort yet they are willing to exert effort to gain rewards. This cost–benefit framework provides predictions for behaviour outside the laboratory. Nevertheless, the extent to which such considerations affect real-life decisions is not clear. Here we experimentally examined computer-programmers' decisions to write code in a reusable manner, using functions, which demands an initial investment of cognitive effort or to clone and tweak code, a strategy whose cost increases with repetitions. Only a small portion of our participants demonstrated sensitivity to the benefits and costs of programming strategies. When asked to solve the tasks, participants tended to avoid using functions, demonstrating biased effort estimation. By contrast, when asked how they
planned
to solve the tasks, participants tended to demonstrate an opposite trend, overestimating effort, in line with an injunctive norm involving the overuse of functions. In the context of real-world problems, the effect of cost–benefit considerations may therefore be limited by task-irrelevant factors. Our interdisciplinary approach may be useful in providing novel theoretical insights and in promoting cognitive-effort investments outside the laboratory.
7-O-Galloyltricetifavan: a promising natural radical scavenger
Authors: Hieu Le Trung , Van Thi Tran Thi , Hoa Nguyen Thi , Mechler Adam , Vo Quan V.
Published: June 2022

7-O-Galloyltricetifavan (
7OGT
), a natural flavonoid, is isolated from the leaves of
Pithecellobium clypearia
. The compound exhibits a variety of biological activities. This study details the evaluation of the HOO
•
antiradical activity of
7OGT
by quantum chemistry calculations. The HOO
•
trapping activity of
7OGT
in the gas phase (reference state) was discovered to follow the formal hydrogen transfer mechanism with a rate constant of
k
= 4.58 × 10
8
M
−1
s
−1
. In physiological environments,
7OGT
is predicted to be an excellent HOO
•
radical scavenger with
k
overall
= 2.65 × 10
8
and 1.40 × 10
4
M
−1
s
−1
in water and pentyl ethanoate solvents, respectively. The HOO
•
antiradical activity of
7OGT
in water at physiological pH is approximately 2000 times that of Trolox and substantially higher than that of other well-known natural antioxidants such as trans-resveratrol or ascorbic acid. Thus,
7OGT
is an excellent natural antioxidant in polar environments.
Evolution of toxins as a public good in phytoplankton
Authors: Ehrlich Elias , Thygesen Uffe Høgsbro , Kiørboe Thomas
Published: June 2022

Toxic phytoplankton blooms have increased in many waterbodies worldwide with well-known negative impacts on human health, fisheries and ecosystems. However, why and how phytoplankton evolved toxin production is still a puzzling question, given that the producer that pays the costs often shares the benefit with other competing algae and thus provides toxins as a ‘public good’ (e.g. damaging a common competitor or predator). Furthermore, blooming phytoplankton species often show a high intraspecific variation in toxicity and we lack an understanding of what drives the dynamics of coexisting toxic and non-toxic genotypes. Here, by using an individual-based two-dimensional model, we show that small-scale patchiness of phytoplankton strains caused by demography can explain toxin evolution in phytoplankton with low motility and the maintenance of genetic diversity within their blooms. This patchiness vanishes for phytoplankton with high diffusive motility, suggesting different evolutionary pathways for different phytoplankton groups. In conclusion, our study reveals that small-scale spatial heterogeneity, generated by cell division and counteracted by diffusive cell motility and turbulence, can crucially affect toxin evolution and eco-evolutionary dynamics in toxic phytoplankton species. This contributes to a better understanding of conditions favouring toxin production and the evolution of public goods in asexually reproducing organisms in general.
GR13-type plasmids in Acinetobacter potentiate the accumulation and horizontal transfer of diverse accessory genes
Authors: Moran Robert A. , Liu Haiyang , Doughty Emma L. , Hua Xiaoting , Cummins Elizabeth A. , Liveikis Tomas , McNally Alan , Zhou Zhihui , van Schaik Willem , Yu Yunsong
Published: June 2022

Carbapenem and other antibiotic resistance genes (ARGs) can be found in plasmids in

Acinetobacter

, but many plasmid types in this genus have not been well-characterized. Here we describe the distribution, diversity and evolutionary capacity of rep group 13 (GR13) plasmids that are found in

Acinetobacter

species from diverse environments. Our investigation was prompted by the discovery of two GR13 plasmids in

A. baumannii

isolated in an intensive care unit (ICU). The plasmids harbour distinct accessory genes: pDETAB5 contains bla
NDM-1 and genes that confer resistance to four further antibiotic classes, while pDETAB13 carries putative alcohol tolerance determinants. Both plasmids contain multiple dif modules, which are flanked by pdif sites recognized by XerC/XerD tyrosine recombinases. The ARG-containing dif modules in pDETAB5 are almost identical to those found in pDETAB2, a GR34 plasmid from an unrelated

A. baumannii

isolated in the same ICU a month prior. Examination of a further 41 complete, publicly available plasmid sequences revealed that the GR13 pangenome consists of just four core but 1186 accessory genes, 123 in the shell and 1063 in the cloud, reflecting substantial capacity for diversification. The GR13 core genome includes genes for replication and partitioning, and for a putative tyrosine recombinase. Accessory segments encode proteins with diverse putative functions, including for metabolism, antibiotic/heavy metal/alcohol tolerance, restriction-modification, an anti-phage system and multiple toxin–antitoxin systems. The movement of dif modules and actions of insertion sequences play an important role in generating diversity in GR13 plasmids. Discrete GR13 plasmid lineages are internationally disseminated and found in multiple

Acinetobacter

species, which suggests they are important platforms for the accumulation, horizontal transmission and persistence of accessory genes in this genus.
Identification and characterization of virus-encoded circular RNAs in host cells
Authors: Chen Shuting , Zheng Jie , Zhang Bingyue , Tang Xinyue , Cun Yewei , Wu Tao , Xu Yue , Ma Ting , Cheng Jingxin , Yu Zuoren , Wang Haiyun
Published: June 2022

Emerging evidence has identified viral circular RNAs (circRNAs) in human cells infected by viruses, interfering with the immune system and inducing diseases including human cancer. However, the biogenesis and regulatory mechanisms of virus-encoded circRNAs in host cells remain unknown. In this study, we used the circRNA detection tool CIRI2 to systematically determine the virus-encoded circRNAs in virus-infected cancer cell lines and cancer patients, by analysing RNA-Seq datasets derived from RNase R-treated samples. Based on the thousands of viral circRNAs we identified, the biological characteristics and potential roles of viral circRNAs in regulating host cell function were determined. In addition, we developed a Viral-circRNA Database (http://www.hywanglab.cn/vcRNAdb/), which is open to all users to search, browse and download information on circRNAs encoded by viruses upon infection.
Predicting neoadjuvant chemotherapy benefit using deep learning from stromal histology in breast cancer
Authors: Li Fengling , Yang Yongquan , Wei Yani , Zhao Yuanyuan , Fu Jing , Xiao Xiuli , Zheng Zhongxi , Bu Hong
Published: June 2022

Neoadjuvant chemotherapy (NAC) is a standard treatment option for locally advanced breast cancer. However, not all patients benefit from NAC; some even get worse outcomes after therapy. Hence, predictors for treatment benefit are crucial for guiding clinical decision-making. Here, we investigated the predictive potentials of breast cancer stromal histology via a deep learning (DL)-based approach and proposed the tumor-associated stroma score (TS-score) for predicting pathological complete response (pCR) to NAC with a multi-center dataset. The TS-score is demonstrated to to be an independent predictor of pCR as it not only outperformed the baseline variables and stromal tumor-infiltrating lymphocytes (sTILs) but also significantly improved the prediction performance of the baseline variable-based model. Further, we discovered that unlike lymphocyte, collagen and fibroblasts in stroma were likely associated with poor response to NAC. The TS-score has potentials to be a candidate for better stratification of breast cancer patients in NAC settings.
Pattern of relapse following three-field lymphadenectomy of esophageal carcinoma and related factors predictive of recurrence
Authors: Xu Zhi-Chen
Published: June 2022

Background

For treatment of esophageal carcinoma, the optimal postoperative radiotherapy target volume after three-field lymph node dissection(3-FLD) had not been determined. We analyzed local recurrence pattern of thoracic esophageal carcinoma and risk factors of lymph node recurrence after 3-FLD without prophylactic radiotherapy.

Methods

We reviewed 1282 patients with thoracic esophageal squamous cell carcinoma(ESCC) who were treated with 3-FLD without radiotherapy from 2010 to 2018 and analysed local recurrence patterns and risk factors of lymph node recurrence, in order to provide a reference for determination of the radiotherapy target volume for thoracic ESCC.

Results

The lymph node recurrence accounted for 91.0% of treatment failures. The mediastinal, cervical and abdominal lymph node recurrence rates were 85.2%, 36.5% and 22.4%, respectively,(x2=264.596, P=0.000). The superior, middle and inferior mediastinal lymph node recurrence rates were 67.54%, 27.87% and 0.98%, respectively(x2=313.600, P=0.000). In a multivariate analysis, Cevical metastases were significantly associated with N stage and Preoperative cevical lymph node status. Abdominal metastases were significantly associated with the number of preoperative abdominal lymph node metastases(LNM), tumor location and N stage.

Conclusions

The main pattern of local-regional recurrence might be lymph node metastasis after radical 3-FLD without radiotherapy in esophageal carcinoma. The dangerous lymph node recurrence regions included neck, superior and middle mediastinum. Radiologist might took the number of pre-operative abdominal lymph nodes and tumor location into consideration while delineating the target area of abdominal region.

This study was supported by Health Department Innovation Fundation Project of Fujian Province (No. 2016-CX-10)
The structure of the humanised A33 Fab C226S variant, an immunotherapy candidate for colorectal cancer
Authors: Tang Jiazhi , Zhang Cheng , Dalby Paul , Kozielski Frank
Published: June 2022

Colorectal cancer (CRC) causes the second highest cancer-related deaths worldwide. The human A33 antigen is a validated immunotherapy target, which is homogeneously expressed in 95% cases of primary and metastatic colorectal cancers. In this article, we report the structure of a humanised antigen-binding fragment A33 (A33 Fab), a therapeutic antibody candidate, in two different crystal forms. Insights into the structural features of A33 Fab are provided with a focus on the ‘grafted’ complementarity-determining regions (CDRs) and the switch linker between the variable and the constant regions.

Synopsis

The crystal structure of humanised A33 Fab, targeting colorectal cancer related antigen, was determined in two different space groups.
Nuclear GAPDH in cortical microglia mediates stress-induced cognitive inflexibility
Authors: Ramos Adriana , Ishizuka Koko , Namkung Ho , Hayes Lindsay N. , Saito Atsushi , Hayashida Arisa , Srivastava Rupali , Elkins Noah , Palen Trexy , Carloni Elisa , Tsujimura Tsuyoshi , Calva Coleman , Ikemoto Satoshi , Rais Rana , Slusher Barbara S. , Niwa Minae , Saitoh Toshiaki , Takimoto Eiki , Sawa Akira
Published: June 2022

We report a mechanism that underlies stress-induced cognitive inflexibility at the molecular level. In a mouse model under subacute stress in which deficits in rule shifting tasks were elicited, the nuclear glyceraldehyde dehydrogenase (N-GAPDH) cascade was activated specifically in microglia in the prelimbic cortex. The cognitive deficits were normalized with a pharmacological intervention with a compound (the RR compound) that selectively blocked the initiation of N-GAPDH cascade without affecting glycolytic activity. The normalization was also observed with a microglia-specific genetic intervention targeting the N-GAPDH cascade. Furthermore, hyperactivation of the prelimbic layer 5 excitatory neurons, which are known to be a neuronal substrate of cognitive inflexibility, was also normalized by the pharmacological and microglia-specific genetic interventions. The RR compound may offer a mechanism-driven, translational opportunity against stress-induced cognitive inflexibility. Taken together, we show a pivotal role of cortical microglia and microglia-neuron interaction in stress-induced cognitive inflexibility. We underscore the N-GAPDH cascade in microglia, which causally mediates stress-induced cognitive alteration.
GenomeBits Characterization of MPXV
Authors: Canessa E.
Published: June 2022

Genome sequences of monkeypox virus (MPVX) causing the current outbreak are being reported from an increasing number of countries. We present a letter-to-numerical sequence study via GenomeBits signal mapping in order to characterize the evolution of the MPXV via simple statistical analysis. Histograms, empirical and theoretical cumulative distribution curves and the resulting scatter plots for the base nucleotides A and C, and their complementary base nucleotides T and G, are discussed. GenomeBits may help on the surveillance of emergent infectious diseases.
WP1066 induces cell death in a schwannomatosis patient–derived schwannoma cell line
Authors: Allaf Abdulrahman , Victoria Berta , Rosario Rosa , Misztal Carly , Humayun Gultekin Sakir , Dinh Christine T. , Fernandez-Valle Cristina
Published: June 2022

Schwannomatosis is a rare genetic disorder that predisposes individuals to development of multiple schwannomas mainly in spinal and peripheral nerves and to debilitating chronic pain often unrelated to any schwannoma. Pathogenic variants of two genes, SMARCB1 and LZTR1, are causal in familial cases. However, many schwannomatosis patients lack mutations in these genes. Surgery is the standard treatment for schwannomas but leaves patients with increasing neurological deficits. Pain management is a daily struggle controlled by the use of multiple analgesic and anti-inflammatory drugs. There is a need for both nonsurgical treatment to manage tumor growth and nonaddictive, nonsedative pain control. Because standard clinical trials are exceedingly difficult for patients with rare disorders, precision medicine approaches offer the possibility of bespoke therapeutic regimens to control tumor growth. As a proof of principle, we obtained a bio-specimen of paraspinal schwannoma from a schwannomatosis patient with a germline point mutation in the SMARCB1/INI gene. We created an hTERT immortalized cell line and tested the ability of targeted small molecules with efficacy in neurofibromatosis type 2–related schwannomas to reduce cell viability and induce cell death. We identified WP1066, a STAT3 inhibitor, currently in phase 2 clinical trials for pediatric and adult brain tumors as a lead compound. It reduced cell viability and STAT-3 phosphorylation and induced expression of markers for both necroptosis and caspase-dependent cell death. The results demonstrate feasibility in creating patient-derived cell lines for use in precision medicine studies.
Unsteady inclined stagnation point flow and thermal transmission of Maxwell fluid on a stretched/contracted plate with modified pressure field
Authors: Bai Yu , Tang Qiaoli , Zhang Yan
Published: June 2022

Purpose

The purpose of this study is to investigate the two-dimensional unsteady inclined stagnation point flow and thermal transmission of Maxwell fluid on oscillating stretched/contracted plates. First, based on the momentum equation at infinity, pressure field is modified by solving first-order differential equation. Meanwhile, thermal relaxation characteristic of fluid is described by Cattaneo–Christov thermal diffusion model.

Design/methodology/approach

Highly coupled model equations are transformed into simpler partial differential equations (PDE) via appropriate dimensionless variables. The approximate analytical solutions of unsteady inclined stagnation point flow on oscillating stretched and contracted plates are acquired by homotopy analysis method for the first time, to the best of the authors’ knowledge.

Findings

Results indicate that because of tensile state of plate, streamline near stagnation point disperses to both sides with stagnation point as center, while in the case of shrinking plate, streamline near stagnation point is concentrated near stagnation point. The enhancement of velocity ratio parameter leads to increasing of pressure variation rate, which promotes flow of fluid. In tensile state, surface friction coefficient on both sides of stagnation point has opposite symbols; when the plate is in shrinkage state, there is reflux near the right side of the stagnation point. In addition, although the addition of unsteady parameters and thermal relaxation parameters reduce heat transfer efficiency of fluid, heat transfer of fluid near the plate can also be enhanced by considering thermal relaxation effect when plate shrinks.

Originality/value

First, approximate analytical solutions of unsteady inclined stagnation point flow on oscillating stretched and contracted plates are researched, respectively. Second, pressure field is further modified. Finally, based on this, thermal relaxation characteristic of fluid is described by Cattaneo–Christov thermal diffusion model.
Affirming who I am: effects of intrinsic and extrinsic affirmations on responses to interpersonal offenses in the workplace
Authors: Deng Mianlin , Li Xiujun , Wang Feng , Shi Wendian
Published: June 2022

Purpose

Previous research has demonstrated that affirming an individual’s self-worth in intrinsic, stable aspects (e.g. personal attributes) enhances their pro-relationship tendencies, as compared to affirming extrinsic aspects of the individual (e.g. performance). This is especially so among people in certain dissatisfying relationships (e.g. romantic relationships). Extending this finding to organizational contexts, the purpose of this study is to investigate the effects of affirmation type (intrinsic vs extrinsic affirmations) on responses to workplace offenses among employees with high versus low job satisfaction.

Design/methodology/approach

Studies 1 (N= 224) and 2 (N= 358) examined the effects of intrinsic versus extrinsic affirmations on responses to hypothetical and real workplace offenses. Furthermore, to compare the effects of intrinsic and extrinsic affirmations to the baseline level, Study 3 (N= 441) added a control condition and examined the effects of affirmation type (intrinsic vs extrinsic vs control) on responses to workplace offenses.

Findings

For employees with low (but not high) job satisfaction, (1) intrinsic (vs extrinsic) affirmations promoted more prosocial responses (forgiveness and reconciliation) to workplace offenses; (2) although not as effective as intrinsic affirmations, extrinsic affirmations (vs baseline) also triggered prosocial intentions toward workplace offenses.

Originality/value

First, the study enriches the literature on workplace offenses by focusing on an individual-level factor – self-worth – that can be intervened (e.g. affirming one’s self-worth) by organizations and managers so as to promote prosocial responses to workplace offenses. Second, the study expands the scope of the self-affirmation theory in organizational contexts by examining the effectiveness of intrinsic and extrinsic affirmations in coping with workplace offenses. Third, practically speaking, the study provides a brief intervention (the writing task of describing an intrinsic or extrinsic affirmation experience) that can boost pro-relationships in the workplace.
Impact of government ownership on private sector enterprises’ environmental responsibility: empirical evidence from Chinese listed firms
Authors: Yu Han , Song Ciji , Song Zengji
Published: June 2022

Purpose

Against the background of actively promoting the reform of mixed ownership in China, this study regards government ownership in private sector enterprises (PSEs) as an important political connection mechanism and examines private holding listed companies in high-polluting industries that sold China A-shares from 2012 to 2019.

Design/methodology/approach

Using regression models such as Tobit and negative binomial estimation, the research empirically examines the impact of government ownership in PSEs on the corporate fulfillment of their environmental responsibilities.

Findings

Government ownership can effectively promote PSEs to fulfill their environmental responsibilities. Government ownership, as a corporate-level political connection mechanism, enables the government to provide firms with more environmental protection subsidies and environmental tax incentives, encouraging firms to fulfill their environmental responsibilities. When considering the policy risks faced by PSEs, government ownership effectively reduces the impact of policy uncertainty on firms’ fulfillment of environmental responsibilities. Additionally, verifying the economic development level of the city in which the firm is located makes the positive impact of government ownership on fulfillment of environmental responsibilities of PSEs in regions with lower economic development levels more significant.

Originality/value

Unlike existing studies that generally use the personal political identity of entrepreneurs to measure the political connections of PSEs, this study regards government ownership in PSEs as an important political connection mechanism. It provides a useful reference for China to formulate environmental protection policies for PSEs.
The effect of team-member knowledge, skills and abilities (KSAs) and a common learning experience on sourcing teamwork effectiveness
Authors: Sanderson Joe , Esfahbodi Ali , Lonsdale Chris
Published: June 2022

Purpose

A lack of sourcing-specific team research prevents a full understanding of sourcing teamwork effectiveness (STE). Moreover, the limited purchasing and supply management (PSM) team literature often tends to focus on an aggregate group level. The paper makes a step towards adopting an individual actor perspective on teamwork effectiveness with an emphasis on the context of sourcing, explicating the effects of team-member knowledge, skills and abilities (KSAs), and examining how these relationships are moderated by a common learning experience of strategic sourcing masterclass.

Design/methodology/approach

Based on a cross-sectional survey, this study analyses a sample of 90 sourcing team members from a global aerospace manufacturing company using hierarchical regression analysis.

Findings

The results suggest that four of the five KSAs positively and significantly affect STE; the exception was collaborative problem solving. Masterclass learning outcomes were found to positively moderate the effects of these KSAs on STE, again exclusive of the collaborative problem-solving KSA.

Research limitations/implications

Cross-sectional design focused only on the aerospace sector may affect generalizability. Further, longitudinal research designs would capture the effects of the common learning experience over an extended period.

Practical implications

Sourcing team members could be selected based on having KSAs which significantly affect teamwork effectiveness. Training and development for sourcing teams should combine guided reflexivity and cross-training to deliver learning outcomes that create similar team mental models.

Originality/value

The study provides an individual team-member perspective on the functioning of sourcing teams which is absent in the extant research. It contributes to the very limited research base on skills in PSM.