bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of next-generation sequencing on diagnosis of bloodstream infection caused by Mycoplasma hominis in a patient with ANCA-associated vasculitis
Authors: Chen Yili , Chen Hengxin , Huang Hao , Zhong Yinyin , Lin Xiaoshu , Chen Peisong , Liao Kang , Yang Juhua , Liu Min , Hong Mengzhi , Wang Ruizhi 
Published: April 2023

Abstract
Background
Mycoplasma hominis is one of the main opportunistic pathogenic mycoplasmas in humans which has a major impact on patients with bloodstream infections. Because it is difficult to detect or isolate, rapid and accurate diagnosis using improved methods is essential and still challenging for patients with bloodstream infection.

Case presentation
In this case, we reported the application of next -generation sequencing for the diagnosis of bloodstream infection caused by Mycoplasma hominis in a patient with Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. After 9 days of combined treatment with levofloxacin, polymyxin B and meropenem, the patient’s condition was gradually controlled and he was discharged without further complications. During the three-month outpatient follow-up, no recurrence of symptoms or clinical signs was reported.

Conclusions
This successful application of next generation sequencing assisted the rapid diagnosis of Mycoplasma hominis bloodstream infection, provided a new perspective in the clinical approach and highlighted the potential of this technique in rapid etiological diagnosis.
PP1γ regulates neuronal insulin signaling and aggravates insulin resistance leading to AD-like phenotypes
Authors: Yadav Yamini , Sharma Medha , Dey Chinmoy Sankar 
Published: April 2023

Abstract
Background
PP1γ is one of the isoforms of catalytic subunit of a Ser/Thr phosphatase PP1. The role of PP1γ in cellular regulation is largely unknown. The present study investigated the role of PP1γ in regulating neuronal insulin signaling and insulin resistance in neuronal cells. PP1 was inhibited in mouse neuroblastoma cells (N2a) and human neuroblastoma cells (SH-SY5Y). The expression of PP1α and PP1γ was determined in insulin resistant N2a, SH-SY5Y cells and in high-fat-diet-fed-diabetic mice whole-brain-lysates. PP1α and PP1γ were silenced by siRNA in N2a and SH-SY5Y cells and effect was tested on AKT isoforms, AS160 and GSK3 isoforms using western immunoblot, GLUT4 translocation by confocal microscopy and glucose uptake by fluorescence-based assay.

Results
Results showed that, in one hand PP1γ, and not PP1α, regulates neuronal insulin signaling and insulin resistance by regulating phosphorylation of AKT2 via AKT2-AS160-GLUT4 axis. On the other hand, PP1γ regulates phosphorylation of GSK3β via AKT2 while phosphorylation of GSK3α via MLK3. Imbalance in this regulation results into AD-like phenotype.

Conclusion
PP1γ acts as a linker, regulating two pathophysiological conditions, neuronal insulin resistance and AD.
Gasdermin E regulates the stability and activation of EGFR in human non-small cell lung cancer cells
Authors: Xu Limei , Shi Feifei , Wu Yingdi , Yao Shun , Wang Yingying , Jiang Xukai , Su Ling , Liu Xiangguo 
Published: April 2023

Abstract
Background
Lung cancer is the most lethal malignancy, with non-small cell lung cancer (NSCLC) being the most common type (~ 85%). Abnormal activation of epidermal growth factor receptor (EGFR) promotes the development of NSCLC. Chemoresistance to tyrosine kinase inhibitors, which is elicited by EGFR mutations, is a key challenge for NSCLC treatment. Therefore, more thorough understanding of EGFR expression and dynamics are needed.

Methods
Human non-small cell lung cancer cells and HEK293FT cells were used to investigate the molecular mechanism of gasdermin E (GSDME) regulating EGFR stability by Western blot analysis, immunoprecipitation and immunofluorescence. GSDME and EGFR siRNAs or overexpression plasmids were used to characterize the functional role of GSDME and EGFR in vitro. EdU incorporation, CCK-8 and colony formation assays were used to determine the proliferation ability of non-small cell lung cancer cells.

Results
GSDME depletion reduced the proliferation of non-small cell lung cancer cells in vitro. Importantly, both GSDME-full length (GSDME-FL) and GSDME-N fragment physically interacted with EGFR. GSDME interacted with cytoplasmic fragment of EGFR. GSDME knockdown inhibited EGFR dimerization and phosphorylation at tyrosine 1173 (EGFRY1173), which activated ERK1/2. GSDME knockdown also promoted phosphorylation of EGFR at tyrosine 1045 (EGFRY1045) and its degradation.

Conclusion
These results indicate that GSDME-FL increases the stability of EGFR, while the GSDME N-terminal fragment induces EGFR degradation. The GSDME-EGFR interaction plays an important role in non-small cell lung cancer development, reveal a previously unrecognized link between GSDME and EGFR stability and offer new insight into cancer pathogenesis.
Spontaneous cancer remission after COVID-19: insights from the pandemic and their relevance for cancer treatment
Authors: Meo Concetta , Palma Giuseppe , Bruzzese Francesca , Budillon Alfredo , Napoli Claudio , de Nigris Filomena 
Published: April 2023

AbstractEarly in the COVID-19 pandemic, it emerged that the risk of severe outcomes was greater in patients with co-morbidities, including cancer. The huge effort undertaken to fight the pandemic, affects the management of cancer care, influencing their outcome. Despite the high fatality rate of COVID-19 disease in cancer patients, rare cases of temporary or prolonged clinical remission from cancers after SARS-CoV-2 infection have been reported. We have reviewed sixteen case reports of COVID-19 disease with spontaneous cancer reduction of progression. Fourteen cases of remission following viral infections and two after anti-SARS-CoV-2 vaccination. The immune response to COVID-19, may be implicated in both tumor regression, and progression. Specifically, we discuss potential mechanisms which include oncolytic and priming hypotheses, that may have contributed to the cancer regression in these cases and could be useful for future options in cancer treatment.
Evaluating key performance indicators of the process of care in juvenile idiopathic arthritis
Authors: Cooper Sarah M. , Currie Gillian R. , Kromm Seija , Twilt Marinka , Marshall Deborah A. 
Published: April 2023

Abstract
Objective
To determine whether and how often the information to measure a set of key performance indicators (KPIs) in juvenile idiopathic arthritis (JIA) is found in data collected routinely in a Pediatric Rheumatology Clinic.

Methods
A retrospective electronic chart review and administrative data analysis was conducted for a cohort of 140 patients with JIA at a tertiary Pediatric Rheumatology Clinic between 2016–2020. The set of KPIs include measuring patient outcomes (joint assessment, physician’s global assessment of disease activity, assessment of functional ability, composite disease activity measurement), access to care (waiting time between referral and first visit, visit with the rheumatologist within the first year of diagnosis, annual follow-up visits with the rheumatologist), and safety (tuberculosis screening, and laboratory monitoring). Documentation was assessed as a binary variable indicating whether the required information was ever found. Documentation frequency for each KPI was assessed with counts and percentages of the number of times the required information was documented for each clinic visit. Compliance with the safety KPI definitions was assessed using administrative databases.

Results
Data for each KPI were found at least once in the cohort and documentation varied in frequency and consistency. Access to care and safety KPIs were documented more frequently than patient outcome KPIs. A joint assessment was documented at every visit for 95% of patients, 46% for an assessment of pain, and none for a physician’s global assessment of disease activity, an assessment of functional ability, or a composite disease activity measurement.

Conclusion
Although feasible to measure, there is an opportunity for improving the consistency of documentation. Having an active system of monitoring KPIs and tools to simplify measurement is a key step in the process toward improved patient care outcomes. Streamlining the collection of KPI data can increase the likelihood of compliance. Next steps should involve replicating this study in various centres.
Estimating the risk of irreversible post-SSRI sexual dysfunction (PSSD) due to serotonergic antidepressants
Authors: Ben-Sheetrit Joseph , Hermon Yehonathan , Birkenfeld Shlomo , Gutman Yehiel , Csoka Antonei B. , Toren Paz 
Published: April 2023

Abstract
Background
Sexual dysfunction is a common side effect of Serotonergic antidepressants (SA) treatment, and persists in some patients despite drug discontinuation, a condition termed post-SSRI sexual dysfunction (PSSD). The risk for PSSD is unknown but is thought to be rare and difficult to assess. This study aims to estimate the risk of erectile dysfunction (ED) and PSSD in males treated with SAs.

Methods
A 19-year retrospective cohort analysis was conducted using a computerized database of the largest HMO in Israel. ED was defined by phosphodiesterase-5 inhibitors prescriptions. 12,302 males aged 21–49 met the following criteria: non-smokers, no medical or psychiatric comorbidities or medications associated with ED, no alcohol or substance use. Logistic regression was used for estimation of ED risk in SA-treated subjects compared to non-SA-treated controls, assessed with and without the effects of age, body mass index (BMI), socioeconomic status (SES), depression and anxiety, yielding crude and adjusted odds ratios (cOR and aOR, respectively).

Results
SAs were associated with an increased risk for ED (cOR = 3.6, p < 0.000001, 95% CI  2.8–4.8), which remained significant after adjusting for age, SES, BMI, depression and anxiety (aOR = 3.2, p < 0.000001, 95% CI  2.3–4.4). The risk for PSSD was 1 in 216 patients (0.46%) treated with SAs. The prevalence of PSSD was 4.3 per 100,000.

Conclusions
This work offers a first assessment of the small but significant risk of irreversible ED associated with the most commonly prescribed class of antidepressants which should enhance the process of receiving adequate informed consent for therapy.
Hyepereosiniphilic syndrome and COVID-19: 2 case reports
Authors: Sherafati Alborz , Rahmanian Mehrzad , Sattarzadeh Badkoubeh Roya , Khoshavi Meysam , Foroumandi Morteza , Peiman Soheil , Shahi Farhad , Sardari Akram , Pourkia Roghayeh , Larti Farnoosh 
Published: April 2023

Abstract
Background
Nearly half of the patients with hypereosinophilic syndrome (HES) have cardiovascular involvement, a major cause of mortality. COVID-19 infection can lead to cardiac involvement, negatively impacting the clinical course and prognosis. We reported two patients with HES complicated by COVID-19, with cardiac involvement and valve replacement.

Case presentation
Our first patient was a 27-year-old woman admitted due to dyspnea and signs of heart failure. She had severe mitral stenosis and mitral regurgitation on the echocardiogram. Corticosteroid therapy improved her symptoms initially, but she deteriorated following a positive COVID-19 test. A repeated echocardiogram showed right ventricular failure, severe mitral regurgitation, and torrential tricuspid regurgitation and, she underwent mitral and tricuspid valve replacement. Our second patient was a 43-year-old man with HES resulted in severe tricuspid stenosis, which was improved with corticosteroid treatment. He underwent tricuspid valve replacement due to severe valvular regurgitation. He was admitted again following tricuspid prosthetic mechanical valve thrombosis. Initial workups revealed lung involvement in favor of COVID-19 infection, and his PCR test was positive.

Conclusion
COVID-19 infection can change the clinical course of HES. It may result in a heart failure exacerbation due to myocardial injury and an increased risk of thrombosis in prosthetic valves or native vessels due to hypercoagulability.
Gab2 plays a carcinogenic role in ovarian cancer by regulating CrkII
Authors: Yin Yi , Zhang Li , Li Yong , Zhang Can , He Aiqin 
Published: April 2023

Abstract
Objective
To detect the expression of Growth factor binding protein 2 associated binding protein 2 (Gab2) and CT10 regulator of kinase II (CrkII) in ovarian cancer and analyze their clinical significance. To explore the effects of Gab2 and CrkII on the biological behavior of ovarian cancer cells. To analyze the possible molecular mechanism of Gab2 in the development of ovarian cancer.

Methods
Immunohistochemistry was used to detect the expression of Gab2 and CrkII in ovarian cancer. Chi square test was used to analyze the correlation between Gab2, CrkII and clinical parameters. Using Cox regression model to evaluate the risk factors affecting the prognosis. To analyze the correlation between Gab2, CrkII and survival rate by Kaplan–Meier. Cell experiments were preformed to explore the effects of Gab2 and CrkII on the biological behavior of cells. The interaction between Gab2 and CrkII was explored by immunoprecipitation.

Results
Immunohistochemistry revealed that high expression of Gab2 and CrkII in ovarian cancer. Patients with high expression of Gab2 or CrkII had higher International Federation of Gynecology and Obstetrics (FIGO) stage, grade and platinum-resistance recurrence. Multivariate analysis showed that Gab2 and CrkII were independent prognostic factors. Kaplan–Meier curve showed that the higher Gab2 and CrkII were, the poor prognosis the patients had. We observed that the overexpression of Gab2 and CrkII promoted the proliferation, metastasis and reduced chemosensitivity of cells. Conversely, the knockdown of Gab2 and CrkII resulted in the opposite results. In CrkII-knockdown cells, we found that Gab2 mediates biological behavior through CrkII.

Conclusions
The expression of Gab2 and CrkII increase in ovarian cancer. The higher expression of Gab2 and CrkII predict the poor prognosis of patients. Gab2 and CrkII promote the proliferation and migration and reduce the chemosensitivity of cells. Gab2 regulates the biological behaviors of ovarian cancer cells through CrkII.
TReating Incontinence for Underlying Mental and Physical Health (TRIUMPH): a study protocol for a multicenter, double-blinded, randomized, 3-arm trial to evaluate the multisystem effects of pharmacologic treatment strategies for urgency-predominant urinary incontinence in ambulatory older women
Authors: Huang Alison J. , Walter Louise C. , Yaffe Kristine , Vittinghoff Eric , Kornblith Erica , Schembri Michael , Chang Ann , Subak Leslee L. 
Published: April 2023

Abstract
Background
Urgency-type urinary incontinence affects one in four older community-dwelling women and overlaps with other common aging-associated health syndromes such as cognitive impairment, physical mobility impairment, and depression. Observational studies have raised concern about potentially higher rates of delirium and dementia in older adults taking anticholinergic bladder medications, but few prospective data are available to evaluate the effects of these and other pharmacologic treatments for urgency incontinence on cognition and other multisystem functional domains important to older women.

Methods
The TRIUMPH study is a randomized, double-blinded, 3-arm, parallel-group trial comparing the multisystem effects of anticholinergic versus beta-3-adrenergic agonist bladder therapy and versus no active bladder anti-spasmodic pharmacotherapy in older women with urgency incontinence. Women aged 60 years and older (target N = 270) who have chronic urgency-predominant urinary incontinence and either normal or mildly impaired cognition at baseline are recruited from the community by investigators based in northern California, USA. Participants are randomized in equal ratios to take identically encapsulated oral anticholinergic bladder therapy (in the form of tolterodine 2 mg extended release [ER]), oral beta-3 adrenergic agonist bladder therapy (mirabegron 25 mg ER), or placebo daily for 24 weeks, with the option of participant-directed dose titration (to tolterodine 4 mg ER, mirabegron 50 mg ER, or matching placebo daily). Participants also receive patient-oriented information and instructions about practicing first-line behavioral management strategies for incontinence. The primary outcome is change in composite cognitive function over 24 weeks assessed by a comprehensive battery of cognitive tests, with a secondary exploration of the persistence of change at 36 weeks. Secondary outcomes include changes over 24 and 36 weeks in domain-specific cognitive function; frequency, severity, and impact of urgency-associated urinary symptoms; physical function and balance; sleep quality and daytime sleepiness; psychological function; and bowel function.

Discussion
The TRIUMPH trial addresses the need for rigorous evidence to guide counseling and decision-making for older women who are weighing the potential multisystem benefits and risks of pharmacologic treatments for urgency incontinence in order to preserve their day-to-day functioning, quality of life, and independence in older age.

Trial registration
ClinicalTrials.gov NCT05362292. Registered on May 5, 2022.
Effect of a customized digital adherence tool on retention in care and adherence to antiretroviral treatment in breastfeeding women, children and adolescents living with HIV in Tanzania: a mixed-methods study followed by clinical trials
Authors: Sumari-de Boer I. Marion , Ngowi Kennedy M. , Swai Iraseni U. , Masika Lyidia V. , Maro Rehema A. , Mtenga Alan E. , Mtesha Benson A. , Nieuwkerk Pythia T. , Reis Ria , de Wit Tobias F. Rinke , Aarnoutse Rob E. 
Published: April 2023

Abstract
Background
Adherence to antiretroviral (ARV) treatment for HIV infection is challenging because of many factors. The World Health Organization (WHO) has recommended using digital adherence technologies (DATs). However, there is limited evidence on how DATs improve adherence. Wisepill® is an internet-enabled medication dispenser found feasible and acceptable in several studies. However, limited evidence is available on its effectiveness in improving ART adherence, specifically among children and adolescents. Furthermore, DATs are often developed without involving the target groups. We propose a two-stage project consisting of a formative study to customize an existing Wisepill DAT intervention and a randomized clinical trial to investigate the effectiveness of DAT combined with reminder cues and tailored feedback on adherence to ARV treatment among children and adolescents living with HIV and retention in care among breastfeeding women living with HIV in Kilimanjaro and Arusha Region, Tanzania.

Methods
We will conduct a formative mixed-methods study and three sub-trials in Kilimanjaro and Arusha Regions among (1) children aged 0–14 years and their caregivers, (2) adolescents aged 15–19 years and (3) breastfeeding women and their HIV-negative infants. In the formative study, we will collect and analyse data on needs and contents for DATs, including the contents of short message service (SMS) texts and tailored feedback. The results will inform the customization of the DAT to be tested in the sub-trials. In the trials, participants will be randomized in the intervention arm, where the DAT will be implemented or the control arm, where standard care will be followed. Participants in the intervention arm will take their medication from the Wisepill box and receive daily reminder texts and tailored feedback during clinic visits.

Discussion
If the intervention improves adherence to ART and the devices are acceptable, accurate and sustainable, the intervention can be scaled up within the National Aids Control Programmes.

Trial registration
PACTR202301844164954, date 27 January 2023.
Familial partial lipodystrophy type 2 and obesity, two adipose tissue pathologies with different inflammatory profiles
Authors: Treiber Guillaume , Gonthier Marie-Paule , Guilleux Alice , Medjane Samir , Bonfanti Oriane , Cogne Muriel , Meilhac Olivier , Nobecourt Estelle 
Published: April 2023

Abstract
Introduction
The transition to metabolically unhealthy obesity (MUO) is driven by the limited expandability of adipose tissue (AT). Familial Partial Lipodystrophy type 2 (FPLD2) is an alternative model for AT dysfunction that is suitable for comparison with obesity. While MUO is associated with low-grade systemic inflammation, studies of inflammation in FPLD2 have yielded inconsistent results. Consequently, comparison of inflammation markers between FPLD2 and obesity is of great interest to better understand the pathophysiological defects of FPLD2.

Objective
To compare the levels of inflammatory biomarkers between a population of patients with FPLD2 due to the same ‘Reunionese’ LMNA variant and a population of patients with obesity (OB group).

Methods
Adiponectin, leptin, IL-6, TNF-α and MCP-1 plasma levels were measured by enzyme-linked immuno assays for 60 subjects with FPLD2 and for 60 subjects with obesity. The populations were closely matched for age, sex, and diabetic status.

Results
Metabolic outcomes were similar between the two populations. Adiponectinemia and leptinemia were lower in the FPLD2 group than in the OB group (p < 0.01 for both), while MCP-1 levels were higher in the FPLD2 than in the OB group (p < 0.01). Levels of other inflammatory markers were not significantly different.

Conclusions
Insulin-resistant patients with FPLD2 and obesity share common complications related to AT dysfunction. Inflammatory biomarker analyses demonstrated that MCP-1 levels and adiponectin levels differ between patients with FPLD2 and patients with obesity. These two AT pathologies thus appear to have different inflammatory profiles.