bluuebunny/crossref_metadata_2025 huggingface dataset:
Rising incidence of HPV positive oropharyngeal cancer in Taiwan between 1999 and 2014 where betel nut chewing is common
Authors: Wang Cheng-Ping , Chen Tseng-Cheng , Hsu Wan-Lun , Hsiao Jenn-Ren , Chen Peir-Rong , Chen Mu-Kuan , Hua Chun-Hung , Tsai Ming-Hsui , Ko Jenq-Yuh , Lou Pei-Jen , Chiang Chun-Ju , Wu Chen-Tu , Chang Yih-Leong
Published: March 2022

Background

The incidence of human papillomavirus (HPV) positive oropharyngeal cancer (OPC) is rising but HPV negative OPC is decreasing in Western countries. In Taiwan, the incidence of HPV negative OPC is common but the incidence of HPV positive OPC remains unknown. The objective of this study is to estimate the incidence trend and the survival of HPV positive OPC in Taiwan.

Methods

Between 1999 and 2014, primary tumor tissues from 425 incident OPCs were obtained from 5 medical centers in Taiwan. 408 OPCs were evaluated by the EasyChip HPV genotyping (King-Car, I-Lan, Taiwan) and 369 OPCs by p16 staining. The clinical data were retrospectively obtained from the medical records.

Results

In our study, 29% of OPCs were HPV positive. The percentage of HPV positive OPC was stable from 1999 to 2014 (25% (1999–2002), 30% (2003–2006), 30% (2007–2010), 29% (2011–2014)). The estimated crude incidence rate of HPV positive OPC increased significantly from 0.62 (1999–2002), 1.06 (2003–2006), 1.52 (2007–2010) to 1.74 (2011–2014) per 100,000 person-year. The sensitivity and specificity of p16 staining for positive HPV infection were 92% and 91%, respectively. The 5-year overall survival rates for patients with HPV positive OPC and with HPV negative OPC were 67.8% and 49.0%, respectively (HR = 0.52 (0.35–0.76), p = 0.0005). Patients with HPV positive OPC but no betel nut/cigarette exposure had the best overall survival (5-year: 88.2%, p < 0.0001). Patients with HPV negative OPC and betel nut/cigarette exposure had the worst overall survival (5-year: 46.6%, p < 0.0001). Patients with HPV positive OPC but also with betel nut/cigarette exposure had poorer 5-year overall survival (48.3%, p < 0.01).

Conclusion

The incidence of HPV positive OPC is increasing along with HPV negative OPC, which leads to stably low percentage of HPV positive OPC in Taiwan. HPV positive OPC may become an important head and neck cancer when the incidence of HPV negative OPC declines in the near future. P16 is a useful surrogate marker for HPV infection in OPC and a good prognostic indicator for treatment outcome of OPC. Patients with HPV positive OPC but no betel nut/cigarette exposure has an excellent prognosis. Betel nut/cigarette exposure significantly worsens the prognosis of HPV positive OPC.
Association between gastric cancer and the risk of depression among South Korean adults
Authors: Kwon Sinyoung , Kim Jinyeong , Kim Taeyeon , Jeong Wonjeong , Park Eun-Cheol
Published: March 2022

Objectives

The diagnosis and treatment of cancer are stressful events that could trigger psychological distress in a large number of cancer patients. The aim of this study was to examine the association between gastric cancer and the risk of new onset of depression among South Korean adults.

Methods

Data from 12,664 participants aged over 40 years was derived from the National Health Service National Sample Cohort (2002–2013). The case cohort consists of patients who received a diagnosis of gastric cancer between 2002 and 2009, and the corresponding control group was selected through 1:1 propensity score matching (case: 6332, control: 6332). The new onset of depression was considered as the dependent variable. A Cox proportional hazards regression model was built to analyze the associations between variables in consideration.

Results

Individuals with gastric cancer had a higher risk of new onset of depression than those without cancer (hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.13–1.45.) Female gastric patients had a higher risk of depression compared to male patients (Female; HR = 1.89, 95% CI = 1.66–2.16, Male; HR = 1.25, 95% CI = 1.10–1.41). Gastric cancer patients in their 60s had the highest risk of new onset of depression compared to other age groups and no cancer group (HR = 1.61, 95% CI = 1.40–1.85). Gastric cancer patients who were previously diagnosed with depression prior to their diagnosis of cancer had a higher risk of new onset of depression than gastric cancer patients without antecedent diagnosis of depression (Past Depression (Yes); HR = 5.17, 95% CI = 4.10–6.51, Past Depression (No); HR = 1.35, CI = 1.21–1.51).

Conclusions

The study identified a significant relationship between gastric cancer and depression among South Korean adults, suggesting that the diagnosis and treatment of gastric cancer increases the risk of new onset of depression, especially among female patients between 60 and 69 years old of high income and living in metropolitan regions. Pre-existing health conditions also appeared to be a risk factor. Thus, in consideration of treatment efficacy and patients’ quality of life, the results of the study emphasizes the need for attentive intervention, while distinguishing the most vulnerable groups.
Adolescent substance use: Findings from a state-wide pilot parent education program
Authors: Nair Nayantara , Elliott Alishia , Arnold Sarah , Flachs Andrew , Beaulieu Barbara , Marceau Kristine
Published: March 2022

Background

Adolescent substance use has long been a top public health priority. In Indiana, concerning recent trends show high rates of youth alcohol consumption coupled with increasing use of opioids, synthetic marijuana, and over-the-counter drugs. Based on research indicating that parent-based prevention efforts may be a particularly effective way to target adolescent substance use, and in a direct effort to address Indiana’s 2017 Strategic Plan to Address Substance Use, we conducted an applied research study targeting parents’ knowledge regarding adolescent substance use in Indiana.

Methods

This community-based applied research study included: (i) a needs assessment of Indiana Extension Educators’ concerns regarding adolescent substance use, (ii) creation and dissemination of an evidence-informed parent education program on adolescent substance use in collaboration with Purdue Extension (a key community stakeholder), and (iii) qualitative focus group discussions at the end of each program that assessed the challenges families face regarding adolescent substance use, the types of information and resources they wish they had, and the usefulness of our program.

Results

The needs assessment revealed that Indiana communities would most benefit from education regarding ways to spot and monitor substance use in teens, and strategies to communicate with teens about substance use. Additionally, Extension Educators thought that existing resources to tackle substance use largely did not match the needs of Indiana communities. Qualitative analysis of the focus group discussions across 8 pilot programs revealed five important themes: (1) The need for current, evidence-informed information regarding adolescent substance use among parents and youth-involved professionals in Indiana, (2) Concern regarding Indiana adolescents’ ease of access to substances and lack of healthy recreational activities, (3) Communicating with teens about substance use is crucial but difficult to implement, (4) Indiana communities’ need to prioritize funding for evidence-informed prevention programming, and (5) The need for community-based parent and caregiver support groups.

Conclusions

Overall, the program was well-received and participants indicated that there was a strong need for this programming in their communities, but suggested collaborating with schools or similar local community stakeholders to increase attendance. Findings from this pilot study can inform future community-based adolescent substance use prevention efforts state-wide.
Access to menstrual hygiene products through incentivised, community-based, peer-led sexual and reproductive health services before and during the COVID-19 pandemic: findings from the Yathu Yathu trial
Authors: B Hensen , M Gondwe , M Phiri , A Schaap , M Simuyaba , S Floyd , L Mwenge , L Sigande , K Shanaube , M Simwinga , S Fidler , R Hayes , H Ayles
Published: March 2022

Background

Access to affordable and effective menstrual hygiene products (MHP) is critical to the menstrual health of adolescent girls and young women (AGYW). In this mixed-methods analysis, we use data from a programme delivering comprehensive sexual and reproductive health (SRH) services to describe access to MHP and how COVID-19-related closures affected access to MHP; we use qualitative data to understand AGYW’s experience accessing products during the study.

Methods

Between September 2019-January 2021, we used data routinely collected from ten Yathu Yathu hubs offering community-based, peer-led SRH services to adolescents and young people aged 15–24. Hubs offered free MHP (primarily disposable pads) as a service. To incentivise service access, a “loyalty” card system was embedded within Yathu Yathu, allowing individuals to gain points for services accessed and redeem rewards using these points. Branded pads, tampons and reusable pads were among available rewards. We describe access to service pads and to reward MHP, and use logistic regression to investigate factors associated with accessing pads and reward products before (Sept 2019-March 2020) and after (July 2020-Jan 2021) COVID-19-related closures. Focus group discussions explored accessibility of offering MHP through hubs.

Results

Between September 2019-January 2021, 6374 AGYW made 34,116 hub visits to access an SRH service and/or redeem a reward. At 30% of these visits, AGYW accessed any MHP. Before COVID19-closures, an average of 17% of monthly visits were for freely-available disposable pads compared to 34% after hubs reopened (p < 0.001). Results were similar for reward visits. Overall, 63% of 6374 AGYW collected pads as a service at least once. Prior to COVID19-closures, AGYW aged 18–24 were more likely to access service pads than adolescents (15–17-years). After reopening, access was lower among older AGYW. Prior to hub closures, uptake of reward MHP was higher among AGYW with some secondary education but not after reopening. Discussions revealed that, for adolescents aged 15–19, COVID-19-related hub closures required reverting to using ineffective materials to manage menstruation.

Conclusion

Availability of MHP through Yathu Yathu provided a large number of AGYW with access to these products. Hubs seemed particularly important for adolescent girls. Community-based, peer-led hubs should be considered as spaces to provide AGYW access to affordable and effective MHP.
Postoperative survival analysis of hepatocellular carcinoma patients with liver cirrhosis based on propensity score matching
Authors: Wu Zhaoqin , Tang Haodong , Wang Lishan , Jin Xiaoling , Lei Zhengqing , Yang Pinghua , Zhou Jiahua
Published: March 2022

Objective

Most hepatocellular carcinoma (HCC) patients in China have some degree of liver cirrhosis. The effect of cirrhosis on the long-term prognosis of HCC patients after hepatectomy is still unclear. This study aimed to investigate the effect of liver cirrhosis on the prognosis of HCC patients after hepatectomy.

Methods

Data from patients who underwent hepatectomy and had pathologically confirmed HCC were retrospectively collected. The patients’ clinical pathological data were recorded. Propensity score matching (PSM) was used to eliminate the influence of potential confounding factors. The Kaplan–Meier method was used to calculate the recurrence-free survival (RFS) and overall survival (OS) rates, and Cox regression analysis was used to screen for independent risk factors affecting OS and RFS.

Results

A total of 1381 HCC patients who were initially treated with hepatectomy were included, including 797 patients with liver cirrhosis. The RFS and OS rates in the group with cirrhosis were significantly lower than those in the group without cirrhosis (after PSM, RFS: P < 0.001; OS: P = 0.001). Subgroup analysis showed that among patients with Barcelona Clinic Liver Cancer (BCLC) stage 0-B disease, RFS and OS were significantly lower in those with cirrhosis than in those without cirrhosis (both P < 0.05); while in patients with stage C disease, there was no significant difference between those with and without cirrhosis. In the group with cirrhosis, alpha-fetoprotein (AFP) > 400, intraoperative blood loss, tumor diameter > 5 cm, satellite lesions, and large vessel invasion were independent risk factors for RFS, while albumin-bilirubin (ALBI) grade, neutrophil-to-lymphocyte ratio (NLR), tumor diameter > 5 cm, satellite lesions, microvascular invasion, and macrovascular invasion were independent risk factors for OS.

Conclusion

HCC with liver cirrhosis has specific characteristics. Compared with patients without cirrhosis, patients with cirrhosis have worse long-term survival after surgery. In addition, the independent risk factors for RFS and OS are different between patients with cirrhosis and without cirrhosis; liver cirrhosis is an independent risk factor for the long-term prognosis of HCC patients, especially patients with BCLC stage 0-B disease after hepatectomy.
The validity of self-reported number of teeth and edentulousness among Norwegian older adults, the HUNT Study
Authors: Høvik Hedda , Kolberg Marit , Gjøra Linda , Nymoen Line Cathrine , Skudutyte-Rysstad Rasa , Hove Lene Hystad , Sun Yi-Qian , Fagerhaug Tone Natland
Published: March 2022

Background

Number of teeth is an established indicator of oral health and is commonly self-reported in epidemiological studies due to the costly and labor-intensive nature of clinical examinations. Although previous studies have found self-reported number of teeth to be a reasonably accurate measure, its accuracy among older adults ≥ 70 years is less explored. The aim of this study was to assess the validity of self-reported number of teeth and edentulousness in older adults and to investigate factors that may affect the accuracy of self-reports.

Methods

This study included two different samples of older adults ≥ 70 years drawn from the fourth wave of the Trøndelag Health Study (the HUNT Study), Norway. Sample 1 (n = 586) was used to evaluate the validity of self-reported number of teeth and sample 2 (n = 518) was used to evaluate self-reported edentulousness. Information on number of teeth and background variables (education, smoking, cognitive function, and self-perceived general and oral health) were self-reported in questionnaires, while clinical oral health examinations assessed number of teeth, number of teeth restored or replaced by fixed prosthodontics and edentulousness. Spearman and Pearson correlation coefficients, Bland–Altman plot, chi-square test and kappa statistics were used to assess the agreement between self-reported and clinically recorded number of teeth.

Results

The mean difference between self-reported and clinically recorded number of teeth was low (− 0.22 teeth), and more than 70% of the participants reported their number of teeth within an error of two teeth. Correlations between self-reports and clinical examinations were high for the total sample (0.86 (Spearman) and 0.91 (Pearson)). However, a lower correlation was found among participants with dementia (0.74 (Spearman) and 0.85 (Pearson)), participants having ≥ 20 teeth (0.76 (Spearman) and 0.67 (Pearson)), and participants with ≥ 5 teeth restored or replaced by fixed prosthodontics (0.75 (Spearman) and 0.77 (Pearson)). Self-reports of having teeth or being edentulous were correct in 96.3% of the cases (kappa value 0.93, p value < 0.001).

Conclusions

Among older Norwegian adults, self-reported number of teeth agreed closely with clinical tooth counts and nearly all the edentulous participants correctly reported having no teeth.
Is adjuvant chemotherapy necessary for young women with early-stage epithelial ovarian cancer who have undergone fertility-sparing surgery?: a multicenter retrospective analysis
Authors: Ikeda Yoshiki , Yoshihara Masato , Yoshikawa Nobuhisa , Yokoi Akira , Tamauchi Satoshi , Nishino Kimihiro , Niimi Kaoru , Kajiyama Hiroaki
Published: March 2022

Objective

In young patients with early-stage epithelial ovarian carcinoma (EOC) who were received fertility-sparing surgery (FSS), the role of adjuvant chemotherapy is unclear. Here, we performed a multicenter study using inverse probability of treatment weighting (IPTW) to explore the effect of chemotherapy on patients’ survival.

Methods

Between 1987 and 2015, a retrospective study was carried out, including 1183 patients with stage I EOC. Among them, a total of 101 women with stage I EOC who underwent FSS were investigated, including 64 and 37 patients with or without adjuvant chemotherapy, respectively. Oncologic outcomes were compared between the two arms using original and IPTW cohorts.

Results

During 62.6 months (median) of follow-up, recurrence was noted in 11 (17.2%) women in the chemotherapy arm and 6 (16.2%) patients in the observation arm. In the unweighted cohort, the 5-year overall and recurrence-free survival (OS/RFS) rates of chemotherapy and observation arms were 86.3/80.8 and 90.2/79.8%, respectively. There was no significant difference between the two groups {Log-rank: P = 0.649 (OS)/P = 0.894 (RFS)}. In the IPTW cohort after adjusting for various clinicopathologic covariates, we also failed to identify a difference in RFS/OS between the two groups {RFS (chemotherapy vs. observation), HR: 0.501 (95% CI 0.234–1.072), P = 0.075: OS (chemotherapy vs. observation), HR: 0.939 (95% CI 0.330–2.669), P = 0.905}.

Conclusions

Even after adjusting clinicopathologic covariates, performing adjuvant chemotherapy may not improve the oncologic outcome in young patients who have undergone FSS.
Discontinuation rates of intrauterine contraception due to unfavourable bleeding: a systematic review
Authors: Costescu Dustin , Chawla Rajinder , Hughes Rowena , Teal Stephanie , Merz Martin
Published: March 2022

Objective

Levonorgestrel-releasing intrauterine devices (LNG-IUDs) and copper intrauterine devices (Cu-IUDs) offer long-acting contraception; however, some women may discontinue use within the first year due to bleeding pattern changes, limiting their potential. This systematic literature review investigated whether differences in bleeding profiles influence continuation rates in women in America, Europe and Australia.

Methods

Searches performed in PubMed and Embase were screened to identify publications describing bleeding patterns and rates of early IUC removal/discontinuation or continuation, descriptions of bleeding patterns, reasons for discontinuation, and patient satisfaction, acceptability and tolerability for LNG-IUDs and Cu-IUDs published between January 2010 and December 2019. The results were further restricted to capture citations related to ‘Humans’ and ‘Females’. The review was limited to studies published from 2010 onwards, as changing attitudes over time mean that results of studies performed before this date may not be generalizable to current practice.

Results

Forty-eight publications describing 41 studies performed principally in the USA (n = 17) and Europe (n = 13) were identified. Publications describing bleeding patterns in LNG-IUD users (n = 11) consistently observed a reduction in bleeding in most women, whereas two of three studies in Cu-IUD users reported heavy bleeding in approximately 40% of patients. Rates of discontinuation for both devices ranged widely and may be as high as 50% but were lower for LNG-IUDs versus Cu-IUDs. Discontinuation rates due to bleeding were consistently higher for Cu-IUDs versus LNG-IUDs.

Conclusions

Bleeding is a common reason for discontinuation of Cu-IUDs and LNG-IUDs. The more favourable bleeding pattern observed in LNG-IUD users may be associated with a lower rate of early discontinuation of LNG-IUDs versus Cu-IUDs.
Evaluation of the association of endometriosis and mammographic breast density, a cross-sectional study
Authors: Moini Ashraf , Salari Elnaz , Rashidi Hadi , Maajani Khadije , Abedi Mahboubeh , Bayani Leila , Alipour Sadaf
Published: March 2022

Background

Endometriosis is a common benign but painful gynecologic condition. Studies suggest that the risk of some types of malignancies such as breast cancer is higher in women with endometriosis. Mammographic breast density (MBD) is known as an important predictor for breast cancer. The present study aimed to investigate the potential relationship between endometriosis and MBD.

Methods

This cross-sectional study was conducted on 370 women over 40 years of age. Laparoscopic surgery was carried out for the diagnosis of endometriosis. MBD was classified into four categories according to the ACR BI-RADS classification. Statistical analysis was performed using SPSS software to evaluate the potential association between variables.

Results

The mean age of all participants was 47.2 ± 6.4 years, and most participants (76.8%) were premenopausal. Multivariate analysis of the potential predictors of MBD, including age, body mass index, oral contraceptive consumption, progesterone consumption, family history of breast cancer and endometriosis showed that age (Pvalue = 0.002), history of progesterone consumption (Pvalue = 0.004) and endometriosis (Pvalue = 0.006) were independent factors for MBD.

Conclusion

This study indicated that endometriosis had an inverse association with MBD. Age and history of progesterone use were also independent influential factors for MBD. This finding shows that the positive association between breast cancer and endometriosis is not mediated through MBD.
Reproductive and postsurgical outcomes of infertile women with deep infiltrating endometriosis
Authors: Zhang Ning , Sun Shugen , Zheng Yunxi , Yi Xiaofang , Qiu Junjun , Zhang Xiaodan , Zhang Ying , Hua Keqin
Published: March 2022

Background

This study aimed to summarize and analyze clinical characteristics and reproductive outcomes in postoperative deep infiltrating endometriosis (DIE).

Methods

This retrospective cohort study included 55 reproductive-aged patients who were diagnosed with DIE, wished to conceive and underwent resection surgery at the Obstetrics and Gynecology Hospital, Fudan University, from January 2009–June 2017. Those with any plausible infertility factor or abnormalities in the partner’s semen analysis were excluded. Patient characteristics, preoperative symptoms, infertility history, intraoperative findings and reproductive outcomes were followed up and recorded. Risk factors for reproductive outcomes were identified for women who became pregnant versus those who did not by univariate logistic regression. Additionally, pre- and postoperative endometriosis health profile questionnaire-30 (EHP-30), Knowles–Eccersley–Scott Symptom questionnaire (KESS), Cox Menstrual Symptom Scale (CMSS) and Female Sexual Function Index (FSFI) scores were used to evaluate the effect of DIE surgery on quality of life.

Results

The average age was 30.22 ± 3.62 years, with no difference between the pregnancy and nonpregnancy groups. The average follow-up time was 26.57 ± 14.51 months. There were 34 pregnancies (61.82%): 24 (70.59%) conceived spontaneously and 10 (29.41%) by in vitro fertilization (IVF). Twenty-eight patients (82.35%) had term deliveries. The interval between operation and pregnancy was 10.33 ± 5.6 (1–26) months. Univariate analysis showed that a lower endometriosis fertility index (EFI) score (EFI < 8) was a risk factor for infertility (OR: 3.17 (1.15–10.14), p = .044). For patients with incomplete surgery, postoperative gonadotropin-releasing hormone agonist (GnRHa) administration improved the pregnancy rate (p < 0.05). Regarding quality of life, there was significant improvement (p < 0.05) in the postoperative EHP-30, KESS and CMSS scores compared with preoperative scores in both groups. Although there was no obvious difference in FSFI scores, significant improvement in dyspareunia was observed (p < 0.05).

Conclusions

Overall, the postoperative pregnancy rate of DIE patients was 61.82%. Surgical management of DIE for patients with complaints of pain and with pregnancy intentions was feasible and effective. Long-term expectant treatment should not be advised for patients with lower EFI scores (EFI < 8), and postoperative IVF–ET may be a good choice. More cases should be enrolled for further study, and randomized studies are required.
Rehabilitation healthcare professionals’ competence and confidence in differentially diagnosing deafblindness from autism spectrum disorders: a cross-sectional survey in South Africa
Authors: Moroe Nomfundo , Masuku Khetsiwe , Shirame Lebogang
Published: March 2022

Background

Early diagnosis and management of children who are deafblind is important to alleviate the effects of deafblindness on the development of the child who is deafblind and their families. However, children who are deafblind are often misdiagnosed or diagnosed late. The misdiagnosis or late diagnosis has been attributed to many factors, one of which is the competence and confidence of healthcare professionals in differentially diagnosing deafblindness from other conditions, in most cases, autism spectrum disorder (ASD). The study therefore aimed to establish the competence and confidence of rehabilitation healthcare professionals in differentially diagnosing deafblindness from ASD in the South African context.

Methods

A cross-sectional survey design was employed for the study. An online questionnaire was distributed to rehabilitation healthcare professionals (N = 78) via Survey Monkey. Data were analyzed using descriptive and inferential statistics. Ethical clearance and permission were obtained from relevant stakeholders prior to the commencement of the study.

Results

Regarding the rehabilitation healthcare professionals in this study, 54% were competent in diagnosing ASD, while only 35% could correctly diagnose deafblindness. In some instances, symptoms were classified as associated with both ASD and deafblindness, when they were just those of deafblindness. Of all the rehabilitation healthcare professionals in this study, speech language therapists displayed the most knowledge of deafblindness. Furthermore, healthcare professionals who had between one and nine years of working experience had more knowledge of deafblindness than other professionals with more or less experience.

Conclusion

Deafblindness is often underdiagnosed or misdiagnosed as ASD. This is due to the lack of competence and confidence of rehabilitation healthcare professionals in diagnosing it. The findings therefore highlight the need for training of rehabilitation healthcare professionals. Training on deafblindness could be included as part of the curriculum in the various undergraduate programs. Deafblindness could also form part of the Continuous Professional Development (CPD) training programs at various healthcare facilities. A team approach to the training would be ideal as it would facilitate peer learning and support. More research is required as it would inform evidence-based assessment, and management and support strategies for children who are deafblind and their families.
GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products
Authors: Smith Andrew J. , Advani Jayshree , Brock Daniel C. , Nellissery Jacob , Gumerson Jessica , Dong Lijin , Aravind L. , Kennedy Breandán , Swaroop Anand
Published: March 2022

Background

Functional complexity of the eukaryotic mitochondrial proteome is augmented by independent gene acquisition from bacteria since its endosymbiotic origins. Mammalian homologs of many ancestral mitochondrial proteins have uncharacterized catalytic activities. Recent forward genetic approaches attributed functions to proteins in established metabolic pathways, thereby limiting the possibility of identifying novel biology relevant to human disease. We undertook a bottom-up biochemistry approach to discern evolutionarily conserved mitochondrial proteins with catalytic potential.

Results

Here, we identify a Parkinson-associated DJ-1/PARK7-like protein—glutamine amidotransferase-like class 1 domain-containing 3A (GATD3A), with bacterial evolutionary affinities although not from alphaproteobacteria. We demonstrate that GATD3A localizes to the mitochondrial matrix and functions as a deglycase. Through its amidolysis domain, GATD3A removes non-enzymatic chemical modifications produced during the Maillard reaction between dicarbonyls and amines of nucleotides and amino acids. GATD3A interacts with factors involved in mitochondrial mRNA processing and translation, suggestive of a role in maintaining integrity of important biomolecules through its deglycase activity. The loss of GATD3A in mice is associated with accumulation of advanced glycation end products (AGEs) and altered mitochondrial dynamics.

Conclusions

An evolutionary perspective helped us prioritize a previously uncharacterized but predicted mitochondrial protein GATD3A, which mediates the removal of early glycation intermediates. GATD3A restricts the formation of AGEs in mitochondria and is a relevant target for diseases where AGE deposition is a pathological hallmark.
Ezetimibe combination therapy with statin for non-alcoholic fatty liver disease: an open-label randomized controlled trial (ESSENTIAL study)
Authors: Cho Yongin , Rhee Hyungjin , Kim Young-eun , Lee Minyoung , Lee Byung-Wan , Kang Eun Seok , Cha Bong-Soo , Choi Jin-Young , Lee Yong-ho
Published: March 2022

Background

The effect of ezetimibe, Niemann-Pick C1-like 1 inhibitor, on liver fat is not clearly elucidated. Our primary objective was to evaluate the efficacy of ezetimibe plus rosuvastatin versus rosuvastatin monotherapy to reduce liver fat using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with non-alcoholic fatty liver disease (NAFLD).

Methods

A randomized controlled, open-label trial of 70 participants with NAFLD confirmed by ultrasound who were assigned to receive either ezetimibe 10 mg plus rosuvastatin 5 mg daily or rosuvastatin 5 mg for up to 24 weeks. The liver fat change was measured as average values in each of nine liver segments by MRI-PDFF. Magnetic resonance elastography (MRE) was used to measure liver fibrosis change.

Results

Combination therapy significantly reduced liver fat compared with monotherapy by MRI-PDFF (mean difference: 3.2%; p = 0.020). There were significant reductions from baseline to study completion by MRI-PDFF for both the combination and monotherapy groups, respectively (18.1 to 12.3%; p < 0.001 and 15.0 to 12.4%; p = 0.003). Individuals with higher body mass index, type 2 diabetes, insulin resistance, and severe liver fibrosis were likely to be good responders to treatment with ezetimibe. MRE-derived change in liver fibrosis was not significantly different (both groups, p > 0.05). Controlled attenuation parameter (CAP) by transient elastography was significantly reduced in the combination group (321 to 287 dB/m; p = 0.018), but not in the monotherapy group (323 to 311 dB/m; p = 0.104).

Conclusions

Ezetimibe and rosuvastatin were found to be safe to treat participants with NAFLD. Furthermore, ezetimibe combined with rosuvastatin significantly reduced liver fat in this population.

Trial registration

The trial was registered at ClinicalTrials.gov (registration number: NCT03434613).
One-year pulmonary impairment after severe COVID-19: a prospective, multicenter follow-up study
Authors: Faverio Paola , Luppi Fabrizio , Rebora Paola , D’Andrea Gabriele , Stainer Anna , Busnelli Sara , Catalano Martina , Modafferi Giuseppe , Franco Giovanni , Monzani Anna , Galimberti Stefania , Scarpazza Paolo , Oggionni Elisa , Betti Monia , Oggionni Tiberio , De Giacomi Federica , Bini Francesco , Bodini Bruno Dino , Parati Mara , Bilucaglia Luca , Ceruti Paolo , Modina Denise , Harari Sergio , Caminati Antonella , Intotero Marcello , Sergio Pietro , Monzillo Giuseppe , Leati Giovanni , Borghesi Andrea , Zompatori Maurizio , Corso Rocco , Valsecchi Maria Grazia , Bellani Giacomo , Foti Giuseppe , Pesci Alberto
Published: March 2022

Background

Long-term pulmonary sequelae following hospitalization for SARS-CoV-2 pneumonia is largely unclear. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 12-month from discharge.

Methods

In this multicentre, prospective, observational study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support (“oxygen only”, “continuous positive airway pressure (CPAP)” and “invasive mechanical ventilation (IMV)”) and followed up at 12 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 min walking test, high resolution CT (HRCT) scan, and modified Medical Research Council (mMRC) dyspnea scale were collected.

Results

Out of 287 patients hospitalized with SARS-CoV-2 pneumonia and followed up at 1 year, DLCO impairment, mainly of mild entity and improved with respect to the 6-month follow-up, was observed more frequently in the “oxygen only” and “IMV” group (53% and 49% of patients, respectively), compared to 29% in the “CPAP” group. Abnormalities at chest HRCT were found in 46%, 65% and 80% of cases in the “oxygen only”, “CPAP” and “IMV” group, respectively. Non-fibrotic interstitial lung abnormalities, in particular reticulations and ground-glass attenuation, were the main finding, while honeycombing was found only in 1% of cases. Older patients and those requiring IMV were at higher risk of developing radiological pulmonary sequelae. Dyspnea evaluated through mMRC scale was reported by 35% of patients with no differences between groups, compared to 29% at 6-month follow-up.

Conclusion

DLCO alteration and non-fibrotic interstitial lung abnormalities are common after 1 year from hospitalization due to SARS-CoV-2 pneumonia, particularly in older patients requiring higher ventilatory support. Studies with longer follow-ups are needed.
High fibrinogen-to-albumin ratio with type 2 diabetes mellitus is associated with poor prognosis in patients undergoing percutaneous coronary intervention: 5-year findings from a large cohort
Authors: Wang Peizhi , Yuan Deshan , Zhang Ce , Zhu Pei , Jia Sida , Song Ying , Tang Xiaofang , Xu Jingjing , Li Tianyu , Zeng Guyu , Zhao Xueyan , Yang Yuejin , Xu Bo , Gao Runlin , Yuan Jinqing
Published: March 2022

Background

Inflammation plays a crucial role in coronary atherosclerosis progression, and growing evidence has demonstrated that the fibrinogen-to-albumin ratio (FAR), as a novel inflammation biomarker, is associated with the severity of coronary artery disease (CAD). However, the long-term risk of cardiovascular events remains indistinct in patients with different level of FAR and different glycemic metabolism status. This study was to assess 5-year clinical outcomes of diabetic and non-diabetic patients who underwent percutaneous coronary intervention (PCI) with different level of FAR.

Methods

We consecutively enrolled 10,724 patients with CAD hospitalized for PCI and followed up for the major adverse cardiac and cerebrovascular events (MACCE) covering all-cause mortality, cardiac mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, and unplanned coronary revascularization. FAR was computed using the following formula: Fibrinogen (g/L)/Albumin (g/L). According to the optimal cut-off value of FAR for MACCE prediction, patients were divided into higher level of FAR (FAR-H) and lower level of FAR (FAR-L) subgroups, and were further categorized into four groups as FAR-H with DM and non-DM, and FAR-L with DM and non-DM.

Results

5298 patients (58.36 ± 10.36 years, 77.7% male) were ultimately enrolled in the present study. A total of 1099 (20.7%) MACCEs were documented during the 5-year follow-up. The optimal cut-off value of FAR was 0.0783 by the surv_cutpoint function. Compared to ones with FAR-H and DM, patients with FAR-L and non-DM, FAR-H and non-DM, FAR-L and DM had decreased risk of MACCEs [adjusted hazard ratio (HR): 0.75, 95% confidence interval (CI) 0.64–0.89, P = 0.001; HR: 0.78, 95% CI 0.66–0.93, P = 0.006; HR: 0.81, 95% CI 0.68–0.97, P = 0.019; respectively]. Notably, non-diabetic patients with lower level of FAR also had lower all-cause mortality and cardiac mortality risk than those in the FAR-H/DM group (HR: 0.41, 95% CI 0.27–0.63, P < 0.001; HR: 0.30, 95% CI 0.17–0.53, P < 0.001; respectively). Multivariate Cox proportional hazards regression analysis also indicated the highest risk of MACCEs in patients with FAR-H and DM than others (P for trend = 0.005). In addition, post-hoc analysis revealed consistent effects on 5-year MACCE across various subgroups.

Conclusion

In this real-world cohort study, higher level of FAR combined with DM was associated with worse 5-year outcomes among patients with CAD undergoing PCI. The level of FAR may help to identify high-risk individuals in this specific population, where more precise risk assessment should be performed.
Antimicrobial activity of ceftazidime-avibactam and comparators against levofloxacin-resistant Escherichia coli collected from four geographic regions, 2012–2018
Authors: Stone Gregory G. , Hackel Meredith A.
Published: March 2022

Background

Increases in resistance to fluoroquinolones have been correlated with the use of levofloxacin in the treatment of infections caused by Escherichia coli. The analysis presents the in vitro activity of ceftazidime-avibactam and comparator agents against 10,840 levofloxacin-resistant E. coli isolates collected from four geographic regions (Africa/Middle East, Europe, Asia/South Pacific, Latin America) between 2012 and 2018.

Methods

Non-duplicate clinical isolates of E. coli were collected from participating centres and shipped to IHMA, Inc., (Schaumburg, IL, USA). Susceptibility testing was performed with frozen broth microdilution panels manufactured by IHMA, according to CLSI guidelines. Levofloxacin-resistance was defined at a minimum inhibitory concentration of ≥ 2 mg/L. Isolates collected between 2012 and 2015 were tested for extended-spectrum β-lactamase (ESBL) activity by determining susceptibility to cefotaxime, cefotaxime-clavulanate, ceftazidime, and ceftazidime-clavulanate as recommended by CLSI guidelines. Isolates collected between 2016 and 2018 were identified as ESBL-positive by genotype using multiplex polymerase chain reaction assays.

Results

A total of 74.8% of levofloxacin-resistant E. coli isolates in the analysis were from three culture sources: urinary tract infections (N = 3229; 29.8%), skin and skin structure infections (N = 2564; 23.7%) and intra-abdominal infections (N = 2313; 21.3%). Susceptibility rates to ceftazidime-avibactam were consistently high in all regions against both ESBL-positive (97.0% in Asia/South Pacific to 99.7% in Africa/Middle East and Latin America) and ESBL-negative isolates (99.4% in Asia/South Pacific to 100% in Latin America). Susceptibility was also high in each region among ESBL-positive and ESBL-negative isolates to colistin (≥ 98.5%), imipenem (≥ 96.5%), meropenem (≥ 96.5%) and tigecycline (≥ 94.1%).

Conclusions

Antimicrobial susceptibility to ceftazidime-avibactam among levofloxacin-resistant E. coli isolates, including ESBL-positive isolates, collected from four geographical regions between 2012 and 2018 was consistently high. Susceptibility to the comparator agents colistin, tigecycline, imipenem and meropenem was also high.
A clinician’s handbook for using ctDNA throughout the patient journey
Authors: Hasenleithner Samantha O. , Speicher Michael R.
Published: March 2022

Background

The promise of precision cancer medicine presently centers around the genomic sequence of a patient’s tumor being translated into timely, actionable information to inform clinical care. The analysis of cell-free DNA from liquid biopsy, which contains circulating tumor DNA (ctDNA) in patients with cancer, has proven to be amenable to various settings in oncology. However, open questions surrounding the clinical validity and utility of plasma-based analyses have hindered widespread clinical adoption.

Main body

Owing to the rapid evolution of the field, studies supporting the use of ctDNA as a biomarker throughout a patient’s journey with cancer have accumulated in the last few years, warranting a review of the latest status for clinicians who may employ ctDNA in their precision oncology programs. In this work, we take a step back from the intricate coverage of detection approaches described extensively elsewhere and cover basic concepts around the practical implementation of next generation sequencing (NGS)-guided liquid biopsy. We compare relevant targeted and untargeted approaches to plasma DNA analysis, describe the latest evidence for clinical validity and utility, and highlight the value of genome-wide ctDNA analysis, particularly as it relates to early detection strategies and discovery applications harnessing the non-coding genome.

Conclusions

The maturation of liquid biopsy for clinical application will require interdisciplinary efforts to address current challenges. However, patients and clinicians alike may greatly benefit in the future from its incorporation into routine oncology care.
Comparative analyses in transcriptome of human granulosa cells and follicular fluid micro-environment between poor ovarian responders with conventional controlled ovarian or mild ovarian stimulations
Authors: Liu Xiaoping , Mai Huisi , Chen Panyu , Zhang Zhiqiang , Wu Taibao , Chen Jianhui , Sun Peng , Zhou Chuanchuan , Liang Xiaoyan , Huang Rui
Published: March 2022

Background

Both mild and conventional controlled ovarian stimulation are the frequently used protocols for poor ovarian responders. However, there are some debates about which treatment is better. Moreover, little is known about the follicular physiology after the two ovarian stimulation protocols. This study was intended to investigate the features in granulosa cells and follicular fluid micro-environment after the two different ovarian stimulation protocols in poor responders.

Methods

Granulosa cells RNA were sequenced using Illumina Hiseq technology. Specific differently expressed genes and proteins were verified by real-time quantitative PCR and Western blot analysis. Moreover, hormone and cytokine concentrations in the follicular fluid were measured by electrochemiluminescence immunoassay and enzyme-linked immunoabsorbent assay. The correlation between the results of molecular experiments and the laboratory outcomes were analyzed by Spearman correlation analysis.

Results

The differentially expressed genes between the two groups were involved in 4 signaling pathways related to the follicular development; three proteins pertinent to the TGF-β signaling pathway were expressed differently in granulosa cells between the two, and the constituents in the follicular fluid were also different. Further, a correlation between the TGF-β signaling pathway and the good-quality embryo was observed.

Conclusions

The present study made a comparison for the first time in the transcriptome of human granulosa cells and the follicular fluid micro-environment between poor responders with the conventional controlled ovarian stimulation or the mild ovarian stimulation, showing that the TGF-β signaling pathway may correlate with the good-quality of embryos in the mild group, which may be instrumental to the choice of optimal management for IVF patients.
The innate immune receptor Nlrp12 suppresses autoimmunity to the retina
Authors: Lee Ellen J. , Napier Ruth J. , Vance Emily E. , Lashley Sydney J. , Truax Agnieszka D. , Ting Jenny P. , Rosenzweig Holly L.
Published: March 2022

Background

Nod-like receptors (NLRs) are critical to innate immune activation and induction of adaptive T cell responses. Yet, their role in autoinflammatory diseases of the central nervous system (CNS) remains incompletely defined. The NLR, Nlrp12, has been reported to both inhibit and promote neuroinflammation in an animal model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE), where its T cell-specific role has been investigated. Uveitis resulting from autoimmunity of the neuroretina, an extension of the CNS, involves a breach in immune privilege and entry of T cells into the eye. Here, we examined the contribution of Nlrp12 in a T cell-mediated model of uveitis, experimental autoimmune uveitis (EAU).

Methods

Mice were immunized with interphotoreceptor retinoid-binding protein peptide 1–20 (IRBP1–20) emulsified in Complete Freund’s adjuvant, CFA. Uveitis was evaluated by clinical and histopathological scoring, and comparisons were made in WT vs. Nlrp12−/− mice, lymphopenic Rag1−/− mice reconstituted with WT vs. Nlrp12−/− CD4+ T cells, or among bone marrow (BM) chimeric mice. Antigen-specific Th-effector responses were evaluated by ELISA and intracellular cytokine staining. Cellular composition of uveitic eyes from WT or Nlrp12−/− mice was compared using flow cytometry. Expression of Nlrp12 and of cytokines/chemokines within the neuroretina was evaluated by immunoblotting and quantitative PCR.

Results

Nlrp12−/− mice developed exacerbated uveitis characterized by extensive vasculitis, chorioretinal infiltrates and photoreceptor damage. Nlrp12 was dispensable for T cell priming and differentiation of peripheral Th1 or Th17 cells, and uveitis in immunodeficient mice reconstituted with either Nlrp12−/− or WT T cells was similar. Collectively, this ruled out T cells as the source of Nlrp12-mediated protection to EAU. Uveitic Nlrp12−/− eyes had more pronounced myeloid cell accumulation than uveitic WT eyes. Transplantation of Nlrp12−/− BM resulted in increased susceptibility to EAU regardless of host genotype, but interestingly, a non-hematopoietic origin for Nlrp12 function was also observed. Indeed, Nlrp12 was found to be constitutively expressed in the neuroretina, where it suppressed chemokine/cytokine induction.

Conclusions

Our data identify a combinatorial role for Nlrp12 in dampening autoimmunity of the neuroretina. These findings could provide a pathway for development of therapies for uveitis and potentially other autoinflammatory/autoimmune diseases of the CNS.