bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding public perceptions in social media responses to posts about acute severe hepatitis of unknown etiology in Indonesia: a qualitative study
Authors: Asa Gregorius Abanit , Fauk Nelsensius Klau , Gesesew Hailay Abrha , Foley Kristen Marie , Lunnay Belinda , Ward Paul Russell
Published: May 2023

Background

Acute Severe Hepatitis of Unknown Etiology (ASHUE) emerged as a new global outbreak in Indonesia early May 2022, coinciding with the COVID-19 pandemic. This study aimed to understand public reactions and responses to the emergence of ASHUE Indonesia and to Government-led disease prevention responses. Understanding how the public perceived government-led preventive messaging about the hepatitis outbreak is crucial to controlling viral spread – particularly given the rapid and unforeseen emergence of ASHUE coincided with COVID-19 and public trust in the Indonesian Government to manage health outbreaks was already tenuous.

Methods

Social media users’ responses to information disseminated via Facebook, YouTube, and Twitter were analyzed to understand public perceptions about ASHUE outbreak and their attitudes toward Government-led prevention measures. Data were extracted on a daily basis from 1st May 2022 to 30th May 2022 and analyzed manually. We inductively generated the codes, from which we formed a construct and then grouped to identify themes.

Results

A total of 137 response comments collected from 3 social medial platforms were analyzed. Of these, 64 were from Facebook, 57 were from YouTube, and 16 were from Twitter. We identified 5 main themes, including (1) disbelief in the existence of the infection; (2) suspicion about a potential new business after COVID-19; (3) suspicion that COVID-19 vaccine(s) are the cause; (4) religion-related fatalism and (5) trust in government measures.

Conclusions

The findings advance knowledge about public perceptions, reactions and attitudes towards the emergence of ASHUE and the efficacy of disease countermeasures. The knowledge from this study will provide an understanding of why disease prevention measures might not be followed. It can be used to develop public awareness programs in Indonesia about both the ASHUE and its possible consequences and the available healthcare support.
Endocarditis due to Aggregatibacter Segnis: a rare case report
Authors: Guo Xiaoxiao , Zhang Xinyun , Qin Yanli , Liu Hong , Wang Xinyu
Published: May 2023

Background

As a member of the HACEK group, Aggregatibacter segnis (A. segnis) is a fastidious Gram-negative coccobacillus that resides in the human oropharyngeal flora. Infective endocarditis caused by A. segnis is rarely reported.

Case presentation

A 31-year-old male was admitted to our hospital for a 3-month history of intermittent high fever, chills, and chest distress. On presentation, he was febrile and tachycardic but otherwise with stable vital signs. Physical examination revealed systolic murmurs in the aortic and mitral valve areas. Pitting edema was evident in the lower extremities. Transthoracic echocardiography demonstrated multiple vegetations in the mitral and aortic valves. Severe regurgitation of the aortic valve and left heart dysfunction were also detected. With the suspicion of infective endocarditis and heart failure, we immediately performed microbiological tests and arranged the cardiac replacement surgery. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and metagenomic next-generation sequencing (mNGS) identified A. segnis from the bloodstream. While the surgical specimen culture was negative, the mNGS was positive for A. segnis. The patient was treated with ceftriaxone for four weeks and discharged. He remained clinically well, with laboratory results restored.

Conclusion

This is the first report of A. segnis infective endocarditis that combined MALDI-TOF and metagenomic next-generation sequencing in the diagnosis. The hypothesis-independent molecular techniques can outperform conventional tools to prevent diagnostic delay.
SABRes: in silico detection of drug resistance conferring mutations in subpopulations of SARS-CoV-2 genomes
Authors: Fong Winkie , Rockett Rebecca J. , Agius Jessica E. , Chandra Shona , Johnson-Mckinnon Jessica , Sim Eby , Lam Connie , Arnott Alicia , Gall Mailie , Draper Jenny , Maddocks Susan , Chen Sharon , Kok Jen , Dwyer Dominic , O’Sullivan Matthew , Sintchenko Vitali
Published: May 2023

The emergence of resistance to antiviral drugs increasingly used to treat SARS-CoV-2 infections has been recognised as a significant threat to COVID-19 control. In addition, some SARS-CoV-2 variants of concern appear to be intrinsically resistant to several classes of these antiviral agents. Therefore, there is a critical need for rapid recognition of clinically relevant polymorphisms in SARS-CoV-2 genomes associated with significant reduction of drug activity in virus neutralisation experiments. Here we present SABRes, a bioinformatic tool, which leverages on expanding public datasets of SARS-CoV-2 genomes and allows detection of drug resistance mutations in consensus genomes as well as in viral subpopulations. We have applied SABRes to detect resistance-conferring mutations in 25,197 genomes generated over the course of the SARS-CoV-2 pandemic in Australia and identified 299 genomes containing resistance conferring mutations to the five antiviral therapeutics that retain effectiveness against currently circulating strains of SARS-CoV-2 – Sotrovimab, Bebtelovimab, Remdesivir, Nirmatrelvir and Molnupiravir. These genomes accounted for a 1.18% prevalence of resistant isolates discovered by SABRes, including 80 genomes with resistance conferring mutations found in viral subpopulations. Timely recognition of these mutations within subpopulations is critical as these mutations can provide an advantage under selective pressure and presents an important step forward in our ability to monitor SARS-CoV-2 drug resistance.
Effectiveness of oral cephalexin in antibiotic-course completion for methicillin-susceptible Staphylococcus aureus-induced bacteremic vertebral osteomyelitis
Authors: Okumura Nobumasa , Hayakawa Kayoko , Yamamoto Kei , Yamada Gen , Mezaki Kazuhisa , Ohmagari Norio
Published: May 2023

Background

Methicillin-susceptible
Staphylococcus aureus (MSSA) is the most common causative microorganism of pyogenic vertebral osteomyelitis (PVO). Although oral antimicrobial therapy with first-generation cephalosporins can treat MSSA infection, data on PVO are scarce. This study evaluated the treatment efficacy of cephalexin as oral antibiotic therapy for MSSA-induced PVO.

Methods

This retrospective study included adult patients treated with oral cephalexin as the completing treatment for PVO with MSSA bacteremia from 2012 to 2020. Treatment effectiveness of cephalexin was evaluated by comparing improvement (5-point scale; score ≥ 4/5 indicates treatment success) in symptoms and laboratory and imaging results between intravenous antimicrobial and oral cephalexin treatment.

Results

Among 15 participants (8 [53%] women; median [interquartile range, IQR], age 75 [67.5–80.5] years; Charlson Comorbidity Index 2 [0–4]), 10 (67%) had lumbar spine lesions, 12 (80%) had spinal abscesses, and 4 (27%) had remote abscesses; no patients had concomitant endocarditis. In 11 patients with normal renal function, cephalexin 1,500–2,000 mg/day was administered. Five patients (33%) underwent surgery. Median (IQR; range) duration (days) of intravenous antibiotics, cephalexin, and total treatment was 36 (32–61; 21–86), 29 (19–82; 8–251), and 86 (59–125; 37–337), respectively. Cephalexin had an 87% treatment success rate without recurrence during a median follow-up of 119 (IQR, 48.5–350) days.

Conclusions

In patients with MSSA bacteremia and PVO, antibiotic treatment completion with cephalexin is a reasonable option, even in cases with spinal abscess, if at least 3 weeks of effective intravenous antimicrobial therapy is provided.
Higher tacrolimus trough levels and time in the therapeutic range are associated with the risk of acute rejection in the first month after renal transplantation
Authors: Nguyen Thi Van Anh , Nguyen Huu Duy , Nguyen Thi Lien Huong , Le Viet Thang , Nguyen Xuan Kien , Tran Viet Tien , Le Dinh Tuan , Ta Ba Thang
Published: May 2023

Background

Tacrolimus trough levels (C0) are used in most transplant centres for therapeutic drug monitoring (TDM) of tacrolimus (Tac). The target range of Tac C0 has been remarkably changed, with a target as low as 3–7 ng/ml in the 2009 European consensus conference and a target of 4–12 ng/ml (preferably to 7–12 ng/ml) following the second consensus report in 2019. Our aim was to investigate whether reaching early Tac therapeutic targets and maintaining time in the therapeutic range (TTR) according to the new recommendations may be necessary for preventing acute rejection (AR) during the first month after transplantation.

Methods

A retrospective study including 160 adult renal transplant patients (113 men and 47 women) with a median age of 36.3 (20–44) years was conducted between January 2018 and December 2019 at 103 Military Hospital (Vietnam). Tac trough levels were recorded in the first month, and episodes of AR were confirmed by kidney biopsy. Tac TTR was calculated as the percentage of time within the target range of 7–12 ng/ml, according to the 2019 second consensus report. Multivariate Cox analysis was performed to identify the correlation between the Tac target range and TTR with AR.

Results

In the first month after RT, 14 (8.8%) patients experienced AR. There was a significant difference in the incidence of AR between the Tac level groups of < 4, 4–7 and > 7 ng/ml (p = 0.0096). In the multivariate Cox analysis, after adjusting for related factors, a mean Tac level > 7 ng/ml was associated with an 86% decreased risk of AR compared with that of 4–7 ng/ml in the first month (HR, 0.14; 95% CI, 0.03–0.66; p = 0.0131). Every 10% increase in TTR was associated with a 28% lower risk of AR (HR, 0.72; 95% CI, 0.55–0.94; p = 0.014).

Conclusion

Gaining and maintaining Tac C0 according to the 2019 second consensus report might reduce the risk of AR in the first month following transplantation.
Inequity of antenatal influenza and pertussis vaccine coverage in Australia: the Links2HealthierBubs record linkage cohort study, 2012–2017
Authors: McHugh Lisa , Regan Annette K , Sarna Mohinder , Moore Hannah C , Van Buynder Paul , Pereira Gavin , Blyth Christopher C , Lust Karin , Andrews Ross M , Crooks Kristy , Massey Peter , Binks Michael J
Published: May 2023

Background

Pregnancy and early infancy are increased risk periods for severe adverse effects of respiratory infections. Aboriginal and/or Torres Strait Islander (respectfully referred to as First Nations) women and children in Australia bear a disproportionately higher burden of respiratory diseases compared to non-Indigenous women and infants. Influenza vaccines and whooping cough (pertussis) vaccines are recommended and free in every Australian pregnancy to combat these infections. We aimed to assess the equity of influenza and/or pertussis vaccination in pregnancy for three priority groups in Australia: First Nations women; women from culturally and linguistically diverse (CALD) backgrounds; and women living in remote areas or socio-economic disadvantage.

Methods

We conducted individual record linkage of Perinatal Data Collections with immunisation registers/databases between 2012 and 2017. Analysis included generalised linear mixed model, log-binomial regression with a random intercept for the unique maternal identifier to account for clustering, presented as prevalence ratios (PR) and 95% compatibility intervals (95%CI).

Results

There were 445,590 individual women in the final cohort. Compared with other Australian women (n = 322,848), First Nations women (n = 29,181) were less likely to have received both recommended antenatal vaccines (PR 0.69, 95% CI 0.67–0.71) whereas women from CALD backgrounds (n = 93,561) were more likely to have (PR 1.16, 95% CI 1.10–1.13). Women living in remote areas were less likely to have received both vaccines (PR 0.75, 95% CI 0.72–0.78), and women living in the highest areas of advantage were more likely to have received both vaccines (PR 1.44, 95% CI 1.40–1.48).

Conclusions

Compared to other groups, First Nations Australian families, those living in remote areas and/or families from lower socio-economic backgrounds did not receive recommended vaccinations during pregnancy that are the benchmark of equitable healthcare. Addressing these barriers must remain a core priority for Australian health care systems and vaccine providers. An extension of this cohort is necessary to reassess these study findings.
Interactive effects of gestational diabetes mellitus and maximum level of total bile acid in maternal serum on adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnancy
Authors: Liao Tingting , Xu Xia , Zhang Yulong , Yan Jianying
Published: May 2023

Objective

To study the combined effect of gestational diabetes mellitus (GDM) and maximum level of maternal serum total bile acid (TBA) on the incidence of adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnancy (ICP).

Methods

This was an observational study with 724 women with ICP. Perinatal outcomes were compared by the presence of GDM. Logistic regression was used to assess the independent and multiplicative interactions of GDM and maximum maternal serum TBA on adverse pregnancy outcomes. Additive interactions were calculated using an Excel sheet developed by Andersson to calculate relative excess risks.

Results

The incidence of GDM in patients with ICP was 21.55%. Maternal age, pre-pregnancy weight, parity, and gravidity were positively correlated with GDM. Hypertensive disorders of pregnancy (HDP) and fetal distress rates were higher in the GDM vs. non-GDM group. There were no significant differences in biochemical outcomes (i.e., Triglyceride (TG), low density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bile acid (TBA)) between the two groups. In terms of adverse pregnancy outcomes, GDM was only associated with maximum TBA concentration for cesarean section. No additive or pairwise interactions were detected between GDM and maximum TBA concentration and HDP, PPH, preterm delivery, LGA, SGA, and cesarean section.

Conclusion

GDM independently contributes to adverse pregnancy outcomes among women with ICP. However, the combined effects of GDM and maximum TBA concentration on adverse pregnancy outcomes do not appear to be multiplicative or additive.
Integrated analysis of circulating and tissue proteomes reveals that fibronectin 1 is a potential biomarker in papillary thyroid cancer
Authors: Ye Guochao , Zhang Xiaomei , Li Mansheng , Lin Zixiang , Xu Yongcan , Dong Haoru , Zhou Jie , Zhang Jiaqi , Wang Sheng , Zhu Yunping , Yu Xiaobo , Qian Xu
Published: May 2023

Papillary thyroid cancer (PTC) is the most frequent subtype of thyroid cancer, but 20% of cases are indeterminate (i.e., cannot be accurately diagnosed) based on preoperative cytology, which might lead to surgical removal of a normal thyroid gland. To address this concern, we performed an in-depth analysis of the serum proteomes of 26 PTC patients and 23 healthy controls using antibody microarrays and data-independent acquisition mass spectrometry (DIA-MS). We identified a total of 1091 serum proteins spanning 10–12 orders of magnitude. 166 differentially expressed proteins were identified that participate in complement activation, coagulation cascades, and platelet degranulation pathways. Furthermore, the analysis of serum proteomes before and after surgery indicated that the expression of proteins such as lactate dehydrogenase A and olfactory receptor family 52 subfamily B member 4, which participate in fibrin clot formation and extracellular matrix-receptor interaction pathways, were changed. Further analysis of the proteomes of PTC and neighboring tissues revealed integrin-mediated pathways with possible crosstalk between the tissue and circulating compartments. Among these cross-talk proteins, circulating fibronectin 1 (FN1), gelsolin (GSN) and UDP-glucose 4-epimerase (GALE) were indicated as promising biomarkers for PTC identification and validated in an independent cohort. In differentiating between patients with benign nodules or PTC, FN1 produced the best ELISA result (sensitivity = 96.89%, specificity = 91.67%). Overall, our results present proteomic landscapes of PTC before and after surgery as well as the crosstalk between tissue and the circulatory system, which is valuable to understand PTC pathology and improve PTC diagnostics in the future.
A real-world study of Afatinib plus ramucirumab in treatment-naïve, EGFR-mutated, non–small cell lung cancer
Authors: Huang Chun-Yao , Huang Hui-Li , Lan Chou-Chin , Huang Yi-Chih , Wu Yao-Kuang
Published: May 2023

Background

Recent reports suggested combining ramucirumab with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) to overcome EGFR resistance in non–small cell lung cancer (NSCLC). Nonetheless, evidence supporting the activity of afatinib and ramucirumab is lacking. This study investigated the survival benefits and safety profile of afatinib plus ramucirumab in patients with treatment-naïve, EGFR-mutated, metastatic NSCLC.

Materials and methods

The medical records of patients with EGFR-mutated NSCLC were retrospectively retrieved. Patients who received first-line sequential afatinib followed by ramucirumab and the first-line combination of afatinib plus ramucirumab were included. The Kaplan-Meier was used to estimate the progression-free survival (PFS) of all included patients, patients on sequential afatinib followed by ramucirumab (PFS1), and patients on the up-front combination of afatinib and ramucirumab (PFS2).

Results

Thirty-three patients were included (25 women; median age: 63 [45–82] years). The median follow-up of the included patients was 17 months (range 6–89 months). the median PFS for the whole cohort was 71 months (95% CI 67.2–74.8) with eight events during the follow-up. The median PFS1 and PFS2 were 71 months (95 CI not defined) and 26 months (95% CI 18.6–33.4), respectively. In terms of OS, the median OS for all patients and patients on sequential treatment was not defined, while the median OS for patients on upfront combination was 30 months (95% CI 20.9–39.1). There was no significant association between EGFR mutation type and PFS1 or PFS2.

Conclusions

Afatinib plus ramucirumab could improve the PFS of patients with EGFR-positive NSCLC at a predictable safety profile. Our data also suggest a survival benefit of adding ramucirumab to afatinib in patients with uncommon mutations, which should be investigated further.
Six addiction components of problematic social media use in relation to depression, anxiety, and stress symptoms: a latent profile analysis and network analysis
Authors: Peng Pu , Liao Yanhui
Published: May 2023

Backgrounds

Components of addiction (salience, tolerance, mood modification, relapse, withdrawal, and conflict) is the most cited theoretical framework for problematic social media use (PSMU). However, studies criticized its ability to distinguish problematic users from engaged users. We aimed to assess the association of the six criteria with depression, anxiety, and stress at a symptom level.

Methods

Ten thousand six hundred sixty-eight participants were recruited. Bergen Social Media Addiction Scale (BSMAS) was used to detect six addiction components in PSMU. We applied the depression-anxiety-stress scale to assess mental distress. Latent profile analysis (LPA) was conducted based on BSMAS items. Network analysis (NA) was performed to determine the symptom-symptom interaction of PSMU and mental distress.

Results

(1) Social media users were divided into five subgroups including occasional users (10.6%, n = 1127), regular users (31.0%, n = 3309), high engagement low risk users (10.4%, n = 1115), at-risk users (38.1%, n = 4070), and problematic users (9.8%, n = 1047); (2) PSMU and mental distress varied markedly across subgroups. Problematic users had the most severe PSMU, depression, anxiety, and stress symptoms. High engagement users scored high on tolerance and salience criteria of PSMU but displayed little mental distress; (3) NA showed conflict and mood modification was the bridge symptoms across the network, while salience and tolerance exhibited weak association with mental distress.

Conclusions

Salience and tolerance might not distinguish engaged users from problematic users. New frameworks and assessment tools focusing on the negative consequences of social media usage are needed.
Impact of tumor contact surface area on collecting system entry in robot-assisted partial nephrectomy: a retrospective analysis
Authors: Umemoto Tatsuya , Hasegawa Masanori , Yuzuriha Soichiro , Kano Tatsuo , Ogawa Takahiro , Kawakami Masayoshi , Nakano Mayura , Kim Hakushi , Nitta Masahiro , Kawamura Yoshiaki , Shoji Sunao , Mizuno Ryuichi , Miyajima Akira
Published: May 2023

Background

Collecting system entry in robot-assisted partial nephrectomy may occur even in cases showing a low N factor in the R.E.N.A.L nephrometry score. Therefore, in this study, we focused on the tumor contact surface area with the adjacent renal parenchyma and attempted to construct a novel predictive model for collecting system entry.

Methods

Among 190 patients who underwent robot-assisted partial nephrectomy at our institution from 2015 to 2021, 94 patients with a low N factor (1–2) were analyzed. Contact surface was measured with three-dimensional imaging software and defined as the C factor, classified as C1, < 10 cm [2]; C2, ≥ 10 and < 15 cm [2]; and C3: ≥ 15 cm [2]. Additionally, a modified R factor (mR) was classified as mR1, < 20 mm; mR2, ≥ 20 and < 40 mm; and mR3, ≥ 40 mm. We discussed the factors influencing collecting system entry, including the C factor, and created a novel collecting system entry predictive model.

Results

Collecting system entry was observed in 32 patients with a low N factor (34%). The C factor was the only independent predictive factor for collecting system entry in multivariate regression analysis (odds ratio: 4.195, 95% CI: 2.160–8.146, p < 0.0001). Models including the C factor showed better discriminative power than the models without the C factor.

Conclusions

The new predictive model, including the C factor in N1-2 cases, may be beneficial, considering its indication for preoperative ureteral catheter placement in patients undergoing robot-assisted partial nephrectomy.
Learning from the COVID-19 pandemic: health care disturbances and telemedicine as an alternative rheumatology practice in Indonesia
Authors: Parlindungan Faisal , Sumariyono Sumariyono , Hidayat Rudy , Wibowo Suryo Anggoro Kusumo , Ariane Anna , Damanik Johanda , Araminta Abirianty Priandani , Yunita Khadijah Cahya
Published: May 2023

Background

Coronavirus disease 2019 (COVID-19) affects health care services. Our aim was to assess health care disruptions, treatment interruptions, and telemedicine reception regarding autoimmune rheumatic diseases (ARDs) in Indonesia.

Method

A cross-sectional population online-based questionnaire was conducted in Indonesia from September to December 2021.

Results

A total of 311 ARD patients were included, of whom 81 (26.0%) underwent consultations via telemedicine during the COVID-19 pandemic. The respondents showed increased concern about their susceptibility to COVID-19 (score of 3.9/5). Approximately 81 (26.0%) avoided hospital visits, and 76 (24.4%) stopped taking the medication without medical advice. Respondents’ concerns correlated with their social distancing behaviors (p value 0.000, r 0.458). Respondent concerns, behaviors, and blocked access to the hospital during the pandemic were associated with avoiding hospital visits (p value 0.014; 0.001; 0.045; 0.008). Sex was associated with stopping medication (p value 0.005). In multivariate analysis, blocked access and sex remained significant. Approximately 81 (26%) respondents who used telemedicine services during the COVID-19 pandemic as an alternative medical consultation method showed high satisfaction (3.8/5).

Conclusion

Health care disruptions and treatment interruptions were affected by patients’ internal and external factors during the COVID-19 pandemic. Telemedicine may be the best option to address barriers to health care access in Indonesia’s rheumatology practice during and after the pandemic situation.
Effectiveness of system navigation programs linking primary care with community-based health and social services: a systematic review
Authors: Teggart Kylie , Neil-Sztramko Sarah E. , Nadarajah Abbira , Wang Amy , Moore Caroline , Carter Nancy , Adams Janet , Jain Kamal , Petrie Penelope , Alshaikhahmed Aref , Yugendranag Shreya , Ganann Rebecca
Published: May 2023

Background

Fragmented delivery of health and social services can impact access to high-quality, person-centred care. The goal of system navigation is to reduce barriers to healthcare access and improve the quality of care. However, the effectiveness of system navigation remains largely unknown. This systematic review aims to identify the effectiveness of system navigation programs linking primary care with community-based health and social services to improve patient, caregiver, and health system outcomes.

Methods

Building on a previous scoping review, PsychInfo, EMBASE, CINAHL, MEDLINE, and Cochrane Clinical Trials Registry were searched for intervention studies published between January 2013 and August 2020. Eligible studies included system navigation or social prescription programs for adults, based in primary care settings. Two independent reviewers completed study selection, critical appraisal, and data extraction.

Results

Twenty-one studies were included; studies had generally low to moderate risk of bias. System navigation models were lay person-led (n = 10), health professional-led (n = 4), team-based (n = 6), or self-navigation with lay support as needed (n = 1). Evidence from three studies (low risk of bias) suggests that team-based system navigation may result in slightly more appropriate health service utilization compared to baseline or usual care. Evidence from four studies (moderate risk of bias) suggests that either lay person-led or health professional-led system navigation models may improve patient experiences with quality of care compared to usual care. It is unclear whether system navigation models may improve patient-related outcomes (e.g., health-related quality of life, health behaviours). The evidence is very uncertain about the effect of system navigation programs on caregiver, cost-related, or social care outcomes.

Conclusions

There is variation in findings across system navigation models linking primary care with community-based health and social services. Team-based system navigation may result in slight improvements in health service utilization. Further research is needed to determine the effects on caregiver and cost-related outcomes.
Patient-level predictors of temporal regularity of primary care visits
Authors: Rose Adam J. , Ahmad Wiessam Abu , Spolter Faige , Khazen Maram , Golan-Cohen Avivit , Vinker Shlomo , Green Ilan , Israel Ariel , Merzon Eugene
Published: May 2023

Background

Patients with chronic diseases should meet with their primary care doctor regularly to facilitate proactive care. Little is known about what factors are associated with more regular follow-up.

Methods

We studied 70,095 patients age 40 + with one of three chronic conditions (diabetes mellitus, heart failure, chronic obstructive pulmonary disease), cared for by Leumit Health Services, an Israeli health maintenance organization. Patients were divided into the quintile with the least temporally regular care (i.e., the most irregular intervals between visits) vs. the other four quintiles. We examined patient-level predictors of being in the least-temporally-regular quintile. We calculated the risk-adjusted regularity of care at 239 LHS clinics with at least 30 patients. For each clinic, compared the number of patients with the least temporally regular care with the number predicted to be in this group based on patient characteristics.

Results

Compared to older patients, younger patients (age 40–49), were more likely to be in the least-temporally-regular group. For example, age 70–79 had an adjusted odds ratio (AOR) of 0.82 compared to age 40–49 (p < 0.001 for all findings discussed here). Males were more likely to be in the least-regular group (AOR 1.18). Patients with previous myocardial infarction (AOR 1.07), atrial fibrillation (AOR 1.08), and current smokers (AOR 1.12) were more likely to have an irregular pattern of care. In contrast, patients with diabetes (AOR 0.79) or osteoporosis (AOR 0.86) were less likely to have an irregular pattern of care. Clinic-level number of patients with irregular care, compared with the predicted number, ranged from 0.36 (fewer patients with temporally irregular care) to 1.71 (more patients).

Conclusions

Some patient characteristics are associated with more or less temporally regular patterns of primary care visits. Clinics vary widely on the number of patients with a temporally irregular pattern of care, after adjusting for patient characteristics. Health systems can use the patient-level model to identify patients at high risk for temporally irregular patterns of primary care. The next step is to examine which strategies are employed by clinics that achieve the most temporally regular care, since these strategies may be possible to emulate elsewhere.
A novel aminotransferase gene and its regulator acquired in Saccharomyces by a horizontal gene transfer event
Authors: Tapia Sebastián M. , Macías Laura G. , Pérez-Torrado Roberto , Daroqui Noemi , Manzanares Paloma , Querol Amparo , Barrio Eladio
Published: May 2023

Background

Horizontal gene transfer (HGT) is an evolutionary mechanism of adaptive importance, which has been deeply studied in wineS. cerevisiaestrains, where those acquired genes conferred improved traits related to both transport and metabolism of the nutrients present in the grape must. However, little is known about HGT events that occurred in wildSaccharomycesyeasts and how they determine their phenotypes.

Results

Through a comparative genomic approach amongSaccharomycesspecies, we detected a subtelomeric segment present in theS. uvarum,S. kudriavzevii, andS. eubayanusspecies, belonging to the first species to diverge in theSaccharomycesgenus, but absent in the otherSaccharomycesspecies. The segment contains three genes, two of which were characterized, namedDGD1andDGD2.DGD1encodes dialkylglicine decarboxylase, whose specific substrate is the non-proteinogenic amino acid 2-aminoisobutyric acid (AIB), a rare amino acid present in some antimicrobial peptides of fungal origin.DGD2encodes putative zinc finger transcription factor, which is essential to induce the AIB-dependent expression ofDGD1. Phylogenetic analysis showed thatDGD1andDGD2are closely related to two adjacent genes present inZygosaccharomyces.

Conclusions

The presented results show evidence of an early HGT event conferring new traits to the ancestor of theSaccharomycesgenus that could be lost in the evolutionary more recentSaccharomycesspecies, perhaps due to loss of function during the colonization of new habitats.
An analysis of DPV and DIVE registry patients with chronic kidney disease according to the finerenone phase III clinical trial selection criteria
Authors: Bramlage Peter , Lanzinger Stefanie , Mühldorfer Steffen , Milek Karsten , Gillessen Anton , Veith Roman , Ohde Tobias , Danne Thomas , Holl Reinhard W. , Seufert Jochen
Published: May 2023

Background

The FIDELIO-DKD and FIGARO-DKD randomized clinical trials (RCTs) showed finerenone, a novel non-steroidal mineralocorticoid receptor antagonist (MRA), reduced the risk of renal and cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Using RCT inclusion and exclusion criteria, we analyzed the RCT coverage for patients with T2DM and CKD in routine clinical practice in Germany.

Methods

German patients from the DPV/DIVE registries who were ≥ 18 years, had T2DM and CKD (an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2OR eGFR ≥ 60 mL/min/1.73m2 and albuminuria [≥ 30 mg/g]) were included. RCT inclusion and exclusion criteria were then applied, and the characteristics of the two populations compared.

Results

Overall, 65,168 patients with T2DM and CKD were identified from DPV/DIVE. Key findings were (1) Registry patients with CKD were older, less often male, and had a lower eGFR, but more were normoalbuminuric vs the RCTs. Cardiovascular disease burden was higher in the RCTs; diabetic neuropathy, lipid metabolism disorders, and peripheral arterial disease were more frequent in the registry. CKD-specific drugs (e.g., angiotensin-converting enzyme inhibitors [ACEi] and angiotensin receptor blocker [ARBs]) were used less often in clinical practice; (2) Due to the RCT’s albuminuric G1/2 to G4 CKD focus, they did not cover 28,147 (43.2%) normoalbuminuric registry patients, 4,519 (6.9%) albuminuric patients with eGFR < 25, and 6,565 (10.1%) patients with microalbuminuria but normal GFR (≥ 90 ml/min); 3) As RCTs required baseline ACEi or ARB treatment, the number of comparable registry patients was reduced to 28,359. Of these, only 12,322 (43.5%) registry patients fulfilled all trial inclusion and exclusion criteria. Registry patients that would have been eligible for the RCTs were more often male, had higher eGFR values, higher rates of albuminuria, more received metformin, and more SGLT-2 inhibitors than patients that would not be eligible.

Conclusions

Certain patient subgroups, especially non-albuminuric CKD-patients, were not included in the RCTs. Although recommended by guidelines, there was an undertreatment of CKD-patients with renin-angiotensin system (RAS) blockers. Further research into patients with normoalbuminuric CKD and a wider prescription of RAS blocking agents for CKD patients in clinical practice appears warranted.
TGF-β1 upregulates secreted protein acidic and rich in cysteine expression in human granulosa-lutein cells: a potential mechanism for the pathogenesis of ovarian hyperstimulation syndrome
Authors: Dang Xuan , Fang Lanlan , Jia Qiongqiong , Wu Ze , Guo Yanjie , Liu Boqun , Cheng Jung-Chien , Sun Ying-Pu
Published: May 2023

Background

Ovarian hyperstimulation syndrome (OHSS) is a serious complication during in vitro fertilization (IVF) treatment. The upregulation of ovarian transforming growth factor-beta 1 (TGF-β1) is involved in the development of OHSS. The secreted protein acidic and rich in cysteine (SPARC) is a secreted multifunctional matricellular glycoprotein. Although the regulatory effects of TGF-β1 on SPARC expression have been reported, whether TGF-β1 regulates SPARC expression in the human ovary remains unknown. In addition, the role of SPARC in the pathogenesis of OHSS is unclear.

Methods

A steroidogenic human ovarian granulosa-like tumor cell line, KGN, and primary culture of human granulosa-lutein (hGL) cells obtained from patients undergoing IVF treatment were used as experimental models. OHSS was induced in rats, and ovaries were collected. Follicular fluid samples were collected from 39 OHSS and 35 non-OHSS patients during oocyte retrieval. The underlying molecular mechanisms mediating the effect of TGF-β1 on SPARC expression were explored by a series of in vitro experiments.

Results

TGF-β1 upregulated SPARC expression in both KGN and hGL cells. The stimulatory effect of TGF-β1 on SPARC expression was mediated by SMAD3 but not SMAD2. The transcription factors, Snail and Slug, were induced in response to the TGF-β1 treatment. However, only Slug was required for the TGF-β1-induced SPARC expression. Conversely, we found that the knockdown of SPARC decreased Slug expression. Our results also revealed that SPARC was upregulated in the OHSS rat ovaries and in the follicular fluid of OHSS patients. Knockdown of SPARC attenuated the TGF-β1-stimulated expression of vascular endothelial growth factor (VEGF) and aromatase, two markers of OHSS. Moreover, the knockdown of SPARC reduced TGF-β1 signaling by downregulating SMAD4 expression.

Conclusions

By illustrating the potential physiological and pathological roles of TGF-β1 in the regulation of SPARC in hGL cells, our results may serve to improve current strategies used to treat clinical infertility and OHSS.
Detection of mild cognitive impairment in Parkinson’s disease using gradient boosting decision tree models based on multilevel DTI indices
Authors: Chen Boyu , Xu Ming , Yu Hongmei , He Jiachuan , Li Yingmei , Song Dandan , Fan Guo Guang
Published: May 2023

Background

Cognitive dysfunction is the most common non-motor symptom in Parkinson’s disease (PD), and timely detection of a slight cognitive decline is crucial for early treatment and prevention of dementia. This study aimed to build a machine learning model based on intra- and/or intervoxel metrics extracted from diffusion tensor imaging (DTI) to automatically classify PD patients without dementia into mild cognitive impairment (PD-MCI) and normal cognition (PD-NC) groups.

Methods

We enrolled PD patients without dementia (52 PD-NC and 68 PD-MCI subtypes) who were assigned to the training and test datasets in an 8:2 ratio. Four intravoxel metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), and two novel intervoxel metrics, local diffusion homogeneity (LDH) using Spearman’s rank correlation coefficient (LDHs) and Kendall’s coefficient concordance (LDHk), were extracted from the DTI data. Decision tree, random forest, and eXtreme gradient boosting (XGBoost) models based on individual and combined indices were built for classification, and model performance was assessed and compared via the area under the receiver operating characteristic curve (AUC). Finally, feature importance was evaluated using SHapley Additive exPlanation (SHAP) values.

Results

The XGBoost model based on a combination of the intra- and intervoxel indices achieved the best classification performance, with an accuracy of 91.67%, sensitivity of 92.86%, and AUC of 0.94 in the test dataset. SHAP analysis showed that the LDH of the brainstem and MD of the right cingulum (hippocampus) were important features.

Conclusions

More comprehensive information on white matter changes can be obtained by combining intra- and intervoxel DTI indices, improving classification accuracy. Furthermore, machine learning methods based on DTI indices can be used as alternatives for the automatic identification of PD-MCI at the individual level.
A vector-free gene interference system using delaminated Mg–Al-lactate layered double hydroxide nanosheets as molecular carriers to intact plant cells
Authors: Zhang He , Li Xinyu , Yu Dong , Guan Junqi , Ding Hao , Wu Hongyang , Wang Qiang , Wan Yinglang
Published: May 2023

Background

The Mg–Al-lactate layered double hydroxide nanosheet (LDH-NS) has shown great potential as an optimal nanocarrier for extensive use in plants. However, previous studies in plant sciences have not provided a clear description of the application for the LDH-NSs-based double-stranded RNA (dsRNA) delivery (LDH-dsRNA) system in different tissues of both model and non-model species.

Results

LDH-NSs were synthesized by using the co-precipitation method, while the dsRNAs targeting genes of interest were prepared in vitro using T7 RNA polymerase. The LDH-dsRNA bioconjugates with a neutral charge were produced by incubating with the mass ratio of LDH-NSs to dsRNA at 3:1, which were then introduced into intact plant cells using three different approaches, including injection, spray, and soak. The LDH-dsRNA delivery method was optimized by inhibiting the expression of the Arabidopsis thaliana ACTIN2 gene. As a result, soaking A. thaliana seedlings in a medium containing LDH-dsRNA for 30 min led to the silencing of 80% of the target genes. The stability and effectiveness of the LDH-dsRNA system were further confirmed by the high-efficiency knockdown of plant tissue-specific genes, including that encoding phytoene desaturase (PDS), WUSCHEL (WUS), WUSCHEL-related homeobox 5 (WOX5), and ROOT HAIR DEFECTIVE 6 (RHD6). In addition, the LDH-dsRNA system was employed in cassava, where it was found that the expression of the gene encoding nucleotide-binding site and leucine-rich repeat (NBS-LRR) was significantly reduced. As a result, the resistance of cassava leaves to pathogens was weakened. Noteworthy, the injection of LDH-dsRNA into leaves resulted in a significant downregulation of target genes in both stems and flowers, indicating the successful transport of LDH-dsRNA from leaves to other parts of plants.

Conclusions

LDH-NSs have proven to be a highly effective molecular tool for delivering dsRNA into intact plant cells, enabling accurate control of target gene expression.
Panax notoginseng saponins inhibits NLRP3 inflammasome-mediated pyroptosis by downregulating lncRNA-ANRIL in cardiorenal syndrome type 4
Authors: Xu Ying , Cao Luxi , Zou Wenli , Yu Rizhen , Shen Wei
Published: May 2023

Objective

Cardiorenal syndrome type 4 (CRS4) is a complication of chronic kidney disease. Panax notoginseng saponins (PNS) have been confirmed to be efficient in cardiovascular diseases. Our study aimed to explore the therapeutic role and mechanism of PNS in CRS4.

Methods

CRS4 model rats and hypoxia-induced cardiomyocytes were treated with PNS, with and without pyroptosis inhibitor VX765 and ANRIL overexpression plasmids. Cardiac function and cardiorenal function biomarkers levels were measured by echocardiography and ELISA, respectively. Cardiac fibrosis was detected by Masson staining. Cell viability was determined by cell counting kit-8 and flow cytometry. Expression of fibrosis-related genes (COL-I, COL-III, TGF-β, α-SMA) and ANRIL was examined using RT-qPCR. Pyroptosis-related protein levels of NLRP3, ASC, IL-1β, TGF-β1, GSDMD-N, and caspase-1 were measured by western blotting or immunofluorescence staining.

Results

PNS improved cardiac function, and inhibited cardiac fibrosis and pyroptosis in a dose-dependent manner in model rats and injured H9c2 cells (p < 0.01). The expression of fibrosis-related genes (COL-I, COL-III, TGF-β, α-SMA) and pyroptosis-related proteins (NLRP3, ASC, IL-1β, TGF-β1, GSDMD-N, and caspase-1) was inhibited by PNS in injured cardiac tissues and cells (p < 0.01). Additionally, ANRIL was upregulated in model rats and injured cells, but PNS reduced its expression in a dose-dependent manner (p < 0.05). Additionally, the inhibitory effect of PNS on pyroptosis in injured H9c2 cells was enhanced by VX765 and reversed by ANRIL overexpression, respectively (p < 0.05).

Conclusion

PNS inhibits pyroptosis by downregulating lncRNA-ANRIL in CRS4.
Home-based enzyme replacement therapy in children and adults with Pompe disease; a prospective study
Authors: Ditters Imke A. M. , van der Beek Nadine A. M. E. , Brusse Esther , van der Ploeg Ans T. , van den Hout Johanna M. P. , Huidekoper Hidde H.
Published: May 2023

Background

Pompe disease is a lysosomal storage disease treated with life-long enzyme replacement therapy (ERT). Home-based ERT has been provided in the Netherlands since 2008 because it diminishes the burden of treatment, increases patient flexibility and autonomy, and is thus a more patient-centred approach to ERT.

Methods

All Dutch Pompe patients receiving alglucosidase alfa infusions at home were approached to participate in a questionnaire to validate the safety of home-based ERT. Prospective data on symptoms occurring during or within 48 h after infusion and retrospective data on infusion associated reactions (IARs) in the last three months were collected four times during one year.

Results

In total, 116 out of 120 eligible patients (17 classic infantile, 2 atypical infantile, 15 childhood onset and 82 adult) filled out 423 questionnaires (response rate: 88.1%). Symptoms during or after infusion were reported 27 times in 17 patients. Fatigue was the most commonly reported health complaint (in 9.5% of patients). Four health complaints were judged to be IARs and reported to the Erasmus MC University Medical Center. None of the IARs reported in this study warranted emergency clinical care.

Conclusions

Our data demonstrate that home-based ERT in Pompe disease can be safely implemented as few, mostly mild, symptoms were reported during or after infusion. Insights from this study can be used as a base for implementing home-based ERT in other countries and to further optimize patient care, as unreported mild symptoms do not pose a health risk but may still be relevant to the patient.
Comparing telemedicine and in-person gastrointestinal cancer genetic appointment outcomes during the COVID-19 pandemic
Authors: Williams Samantha , Ebrahimzadeh Jessica E. , Clay Daniel , Constantino Gillian , Heiman Jordan , Wangensteen Kirk J. , Valverde Kathleen , Mahmud Nadim , Katona Bryson W.
Published: May 2023

Background

The study purpose is to compare outcomes associated with completion of genetic testing between telemedicine and in-person gastrointestinal cancer risk assessment appointments during the COVID-19 pandemic.

Methods

Data was collected on patients with scheduled appointments between July 2020 and June 2021 in a gastrointestinal cancer risk evaluation program (GI-CREP) that utilized both telemedicine and in-person visits throughout the COVID-19 pandemic, and a survey was administered.

Results

A total of 293 patients had a GI-CREP appointment scheduled and completion rates of in-person versus telemedicine appointments were similar. Individuals diagnosed with cancer and those with Medicaid insurance had lower rates of appointment completion. Although telehealth was the preferred visit modality, there were no differences in recommending genetic testing nor in the consent rate for genetic testing between in-person and telemedicine visits. However, of patients who consented for genetic testing, more than three times more patients seen via telemedicine did not complete genetic testing compared to those seen in-person (18.3% versus 5.2%, p = 0.008). Furthermore, telemedicine visits had a longer turnaround time for genetic test reporting (32 days versus 13 days, p < 0.001).

Conclusions

Compared to in-person GI-CREP appointments, telemedicine was associated with lower rates of genetic testing completion, and longer turnaround time for results.