bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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

AbstractNeoadjuvant 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

AbstractBackgroundFor 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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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

AbstractColorectal 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.SynopsisThe 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

ABSTRACTWe 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.
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

PurposePrevious 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/approachStudies 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.FindingsFor 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/valueFirst, 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.