bluuebunny/crossref_metadata_2025 huggingface dataset:
Review of Integrative Medical Therapies for Psoriasis: The Microbiome, Probiotics, Diet, and Mindfulness
Authors: Min Mildred , Dulai Ajay S. , Ahmad Nabeel , Sivamani Raja K.
Published: February 2024

Background

Psoriasis is a chronic inflammatory condition with cutaneous and systemic involvement. Although many efficacious treatment options are available, concerns regarding costs and duration of treatment have expanded interest in the role of integrative medical therapies for psoriasis.

Objective

In this review, we aim to provide evidence for the use of integrative medical approaches in the management of psoriasis, namely approaches utilizing the microbiome, probiotics, diet, and mindfulness.

Methods

PubMed/Medline and Google Scholar databases were searched from inception up to 16 August 2023 to identify clinical studies that evaluated how integrative medical therapies affect psoriasis severity. Search terms combined “psoriasis” or “psoriatic arthritis” with terms related to the microbiome, diet, and lifestyle.

Results

Multiple clinical studies have shown that integrative approaches can reduce psoriasis severity. Probiotic supplementation in psoriatic patients decreased PASI scores, decreased inflammatory markers, increased quality of life, and reduced the risk of disease relapse. Intermittent fasting, in the context of Ramadan, decreased PASI scores and plasma CRP levels. Low-calorie diets and low-calorie ketogenic diets have been shown to reduce psoriasis severity. Notably, combining low-calorie diets with biologics and cyclosporine synergistically improved psoriasis to a greater extent than pharmaceutical therapy alone. A gluten-free diet improved psoriasis and reduced antigliadin antibodies in those with hypersensitivity. Mindfulness therapies also improved psoriasis severity with and without phototherapy.

Conclusion

Several studies show that integrative medicine can be used to manage psoriasis. Specifically, probiotic supplementation, diets that promote weight loss or modulate antigliadin antibodies, and mindfulness therapies may improve disease severity.
Concordance between nice classification and histopathology in colonic polyps: a tertiary center experience
Authors: Buitrago-Tamayo Andrea C. , Lombo-Moreno Carlos E. , Ursida Valentina , Leguizamo-Naranjo Ana M. , Muñoz-Velandia Oscar M. , Vargas-Rubio Rómulo D.
Published: February 2024

Background:

Narrow-Band imaging International Colorectal Endoscopic (NICE) could reduce histopathology study requirements in colorectal polyp evaluation. Local and regional studies are required to validate its utility.

Objectives:

To evaluate concordance between NICE classification and histopathology.

Design:

Prospective analytic study performed in the Hospital Universitario San Ignacio, Bogotá (Colombia) between 2021 and 2022.

Methods:

Concordance between NICE I, II and III classification and histopathology [Hyperplastic Polyp (HP), adenoma and deep submucosal invasive cancer (DSIC)] was evaluated using weighted kappa. Diagnostic performance was evaluated for NICE I–II versus NICE III for DSIC versus adenoma/HP. A subgroup analysis was performed for polyps ⩾10 mm and those located in the rectum, sigmoid, and left colon.

Results:

A total of 238 polyps from 135 patients were evaluated. Median age 67 years (IQR 58.5–74.5), 54.4% males. 23 (17.1%) had ⩾3 polyps. Of polyps, 52.1% were located on rectum, sigmoid and left colon. A total of 182 (76.5%) were <10 mm. NICE and histopathology evidenced a fair-moderate concordance (quadratic weighted kappa 0.36, linear weighted kappa 0.43). NICE classification (NICE I–II versus III) compared to histopathology (DSIC versus adenoma/HP) evidenced a sensitivity of 90.9% and specificity of 99.1%. For DSIC diagnosis specificity was ⩾95% on polyps ⩾10 mm and those left sided located.

Conclusion:

NICE and histopathology concordance is suboptimal. However, NICE III for DSIC diagnosis evidence good specificity. Therefore, NICE III polyps require a prompt histopathological evaluation and follow-up. Good operative characteristics stand in polyps ⩾10 mm and left sided located. NBI formal training is recommended in gastroenterology units in Latin America.
G protein-coupled estrogen receptor activates PI3K/AKT/mTOR signaling to suppress ferroptosis via SREBP1/SCD1-mediated lipogenesis
Authors: Chen Jiaping , Zhao Rong , Wang Yangwei , Xiao Han , Lin Wei , Diao Mingxin , He Shiwen , Mei Peiyuan , Liao Yongde
Published: February 2024

Background

Lung cancer is the leading cause of cancer-related death worldwide. The sex differences in the occurrence and fatality rates of non-small cell lung cancer (NSCLC), along with its association with estrogen dependence, suggest that estrogen receptors (ERs) contribute to the development of NSCLC. However, the influence of G protein-coupled estrogen receptor (GPER1) on NSCLC remains to be determined. Escape from ferroptosis is one of the hallmarks of tumor discovered in recent years. In this context, the present study evaluated whether GPER1 promotes NSCLC progression by preventing ferroptosis, and the underlying mechanism through which GPER1 protects against ferroptosis was also explored.

Methods

The effects of GPER1 on the cytotoxicity of H2O2, the ferroptosis inducer RSL3, and Erastin were assessed using the CCK8 assay and plate cloning. Lipid peroxidation levels were measured based on the levels of MDA and BODIPY™581/591C11. GPER1 overexpression and knockdown were performed and G1 was used, and the expression of SCD1 and PI3K/AKT/mTOR signaling factors was measured. Immunofluorescence analysis and immunohistochemistry were performed on paired specimens to measure the correlation between the expression of GPER1 and SCD1 in NSCLC tissues. The effect of GPER1 on the cytotoxicity of cisplatin was measured in vitro using the CCK8 assay and in vivo using xenograft tumor models.

Results

GPER1 and G1 alleviated the cytotoxicity of H2O2, reduced sensitivity to RSL3, and impaired lipid peroxidation in NSCLC tissues. In addition, GPER1 and G1 promoted the protein and mRNA expression of SCD1 and the activation of PI3K/AKT/mTOR signaling. GPER1 and SCD1 expression were elevated and positively correlated in NSCLC tissues, and high GPER1 expression predicted a poor prognosis. GPER1 knockdown enhanced the antitumor activity of cisplatin in vitro and in vivo.

Conclusion

GPER1 prevents ferroptosis in NSCLC by promoting the activation of PI3K/AKT/mTOR signaling, thereby inducing SCD1 expression. Therefore, treatments targeting GPER1 combined with cisplatin would exhibit better antitumor effects.

Graphical Abstract
Regulation of myocardial contraction as revealed by intracellular Ca2+ measurements using aequorin
Authors: Kurihara Satoshi , Fukuda Norio
Published: February 2024

Of the ions involved in myocardial function, Ca2+ is the most important. Ca2+ is crucial to the process that allows myocardium to repeatedly contract and relax in a well-organized fashion; it is the process called excitation–contraction coupling. In order, therefore, for accurate comprehension of the physiology of the heart, it is fundamentally important to understand the detailed mechanism by which the intracellular Ca2+ concentration is regulated to elicit excitation–contraction coupling. Aequorin was discovered by Shimomura, Johnson and Saiga in 1962. By taking advantage of the fact that aequorin emits blue light when it binds to Ca2+ within the physiologically relevant concentration range, in the 1970s and 1980s, physiologists microinjected it into myocardial preparations. By doing so, they proved that Ca2+ transients occur upon membrane depolarization, and tension development (i.e., actomyosin interaction) subsequently follows, dramatically advancing the research on cardiac excitation–contraction coupling.
Effect of esketamine on the EC50 of remifentanil for blunting cardiovascular responses to endotracheal intubation in female patients under general anesthesia: a sequential allocation dose-finding study
Authors: Ziqiang Fan , Keyu He , Yun Xue , Li Liu , Yiping Bai
Published: February 2024

Background

This study aimed to investigate the effect of esketamine on the dose–effect relationship between remifentanil and the cardiovascular response to endotracheal intubation during target-controlled infusion (TCI) of propofol.

Methods

Patients underwent elective gynecological laparoscopic surgery under general anesthesia with endotracheal intubation, aged 18–65 years, American Society of Anesthesiologists class I or II, 18 kg/m2 ≤ body mass index ≤ 30 kg/m2, were randomly divided into the control (group C) and esketamine groups (group E). Before anesthesia induction, group E received an intravenous injection of 0.3 mg/kg of esketamine, while group C received an equal dose of physiological saline. TCI of propofol to the effect-site concentration (EC) of 3.0 μg/mL, and then TCI of remifentanil to the effect room and intravenous injection of rocuronium 0.6 mg/kg after MOAA/S was 0. Endotracheal intubation was performed after 2 min. Dixon’s modified sequential method was used, and the initial EC of remifentanil was 3.0 ng/mL. The EC of remifentanil was determined according to the intubation response of the previous patient, with an adjacent concentration gradient of 0.3 ng/mL. The EC50 and EC95 values and their 95% confidence intervals (CIs) were determined using probit regression analysis.

Results

The EC50 for cardiovascular response inhibition to endotracheal intubation using remifentanil was 3.91 ng/mL (95% CI: 3.59–4.33 ng/mL) and EC95 was 4.66 ng/mL (95% CI: 4.27–6.23 ng/mL) with TCI of propofol 3.0 μg/mL. After intravenous administration of 0.3 mg/kg of esketamine, the EC50 of remifentanil was 3.56 ng/mL (95% CI: 3.22–3.99 ng/mL) and EC95 was 4.31 ng/mL (95% CI: 3.91–5.88 ng/mL).

Conclusions

Combined with TCI of propofol 3.0 μg/mL for anesthesia induction, esketamine significantly reduced the EC50 and EC95 of remifentanil to inhibit the cardiovascular response to endotracheal intubation.

Trial registration

The trial was registered in the Chinese Clinical Trials Registry (www.chictr.org.cn; registration number: ChiCTR2200064932; date of registration:24/10/2022).
Youth preferences for healthcare providers and healthcare interactions: a qualitative study
Authors: Waselewski Marika , Amaro Xochitl , Huerto Ryan , Berger Jessica , Spinelli da Silva Marcus , Siroky Kate , Torres Anthony , Chang Tammy
Published: February 2024

Background

Patient-physician relationships in healthcare can influence healthcare provision, patient engagement, and health outcomes. Little is known about youth preferences on types and characteristics of their healthcare providers. The aim of this study was to assess youth perspectives on preferences for and interactions with their healthcare providers.

Methods

We posed 5 open-ended questions to 1,163 MyVoice participants, a nationwide text message cohort of United States youth aged 14–24, on April 10, 2020 related to youth preferences for healthcare providers. Content analysis was used to develop a codebook. Responses were independently coded by two reviewers with discrepancies discussed to reach consensus. Descriptive statistics were calculated for demographics and frequency of codes.

Results

944 (81%) participants responded to at least one question. Respondents had a mean age of 18.9 years (SD: 2.8) and were a majority female (53.6%) and White (56.3%). Youth reported “kindness” or other personality traits (31%) and education (30%) as important in choosing their doctor. Patient-physician concordance was not important to many youths (44%) and among those who reported concordance as important (55%), having the same gender was the most noted (68%). Youth suggested respect, open conversation, and addressing issues directly to help alleviate uncomfortable situations, though some would simply switch providers.

Conclusion

Personality and empathy are important provider characteristics valued by youth. Female respondents preferred gender concordant providers, particularly for sexual health-related issues, and non-white respondents were more likely to prefer racial concordance. Strengthening professional and interpersonal skills among youth-serving providers may improve healthcare engagement and satisfaction among youth.
The effectiveness of hysteroscopy for the treatment of cesarean scar pregnancy: a retrospective cohort study
Authors: You Xinxin , Ruan Yan , Weng Shouxiang , Lin Chenya , Gan Meifu , Qi Feng
Published: February 2024

Background

Cesarean scar pregnancy (CSP) is a long-term complication of cesarean section characterized by the localization of a subsequent gestational sac within the scar area or niche developed as a result of a previous cesarean section. Its incidence has increased substantially because of the high global cesarean section rate in recent decades. Several surgical and drug treatments exist for this condition; however, there is currently no optimal treatment. This study compared the effectiveness of direct hysteroscopic removal of the gestational tissue and hysteroscopy combined with vacuum suction for the treatment of CSP.

Methods

From 2017 to 2023, 521 patients were diagnosed with CSP at our hospital. Of these patients, 45 underwent hysteroscopy. Among them, 28 underwent direct hysteroscopic removal (hysteroscopic removal group) and 17 underwent hysteroscopy combined with vacuum suction (hysteroscopic suction group). The clinical characteristics and outcomes of the hysteroscopic removal group and hysteroscopic suction group were analyzed.

Results

Among the 45 patients, the amount of bleeding and hospitalization cost were significantly higher in the hysteroscopic removal group than in the hysteroscopic suction group (33.8 mL vs. 9.9 mL, P < 0.001; and 8744.0 yuan vs. 5473.8 yuan, P < 0.001; respectively). The operation time and duration of hospitalization were significantly longer in the hysteroscopic removal group than in the hysteroscopic suction group (61.4 min vs. 28.2 min, P < 0.001; and 3.8 days vs. 2.4 days, P = 0.026; respectively). Three patients in the hysteroscopic removal group had uterine perforation and received laparoscopic repair during operation. No complications occurred in the hysteroscopic suction group. One patient in the hysteroscopic removal group received ultrasound-guided suction curettage due to postoperative moderate vaginal bleeding, and one patient in the hysteroscopic suction group received ultrasound-guided suction curettage due to postoperative gestational residue and elevated serum beta-human chorionic gonadotropin levels. Reproductive function was preserved in all patients.

Conclusions

Hysteroscopy is an effective method for treating CSP. Compared with direct hysteroscopic removal, hysteroscopy combined with vacuum suction is more suitable for CSP. However, multicenter prospective studies with large sample sizes are required for verification of these findings.
The association between the diversity of online activities on smartphones and cognitive function among middle-aged and elderly Chinese adults
Authors: Chen Qian , Ji Haoqiang , Shang Qingxin
Published: February 2024

Background

Many studies have shown that using smartphones can improve cognitive function, but no studies have shown the effect of the diversity of online activities on cognitive function. Therefore, this study explores the association between the diversity of online activity on smartphones and cognitive function among middle-aged and elderly Chinese adults.

Methods

A total of 13,347 Chinese middle-aged and elderly participants were used in the final analysis. Multivariate linear regression models were used to explore the relationships among the frequency of smartphone use, number of online activities, various activities, and cognitive function.

Results

We found that 2,143 respondents (16.1%) used smartphones, and the top three online activities were watching news (80.3%), posting moments (72.4%), and chatting (68.0%) among all smartphone users to access the internet. After adjusting for all covariates, we found that the increase in the frequency of smartphone use and the number of online activities were correlated with a higher cognitive score. Moreover, some online activities, such as watching news (β:0.5, 95% CI:0.2–0.8), posting moments (β:0.4, 95% CI:0.2–0.7) playing games (β:0.3, 95% CI:0.03–0.6) and making mobile payments (β:0.3, 95% CI:0.1–0.5) were independently associated with good cognitive function.

Discussion

In the middle-aged and elderly population, smartphone use plays an important role in cognitive function. Considering the increasing prevalence of smartphones among middle-aged and elderly individuals, this study can provide references and insights for health education and in-depth scientific research related to internet usage.
Evaluation of single and multiple hyaluronic acid injections at different concentrations with high molecular weight in the treatment of knee osteoarthritis
Authors: Safali Selim , Ertaş Erkan Sabri , Özdemir Ali , Cataklı Deniz
Published: February 2024

Background

Knee osteoarthritis is severe progressive and most commonly diagnosed articular disease and its incidence is increasing around the world depending on age. This pathologic condition which limits daily activity of patients can be characterized by degeneration of cartilage and inflammation. Although non-steroidal anti-inflammatory (NSAII) agents and other analgesics are routinely used treatment options, the potential effects of intraarticular injections including hyaluronic acid (HA) have also been demonstrated by various studies. However, few studies compare the efficacy of a single high molecular weight (HMW) high dose and a triple HMW low dose. This study aimed to compare the efficacy of single high molecular weight (HMW) high dose (2 mL / 60 mg) and triple HMW low dose (2 mL /30 mg) intra-articular injection of HA in knee osteoarthritis (OA) patients by evaluating function and pain parameters during 12 months.

Methods

This is a single-center, retrospective clinical study that included and involved 128 patients. Group I (n=64) patients received triple 30 mg HA injections (SEMICAL®) with one-week intervals, while Group II (n=64) patients received a single 60 mg HA injection (SEMICAL®). Lequesne Index, WOMAC and VAS scores were recorded to assess pain and function during a 12-month period.

Results

There was no significant difference in characteristics of patient demographics. Our finding indicate that WOMAC, VAS score, and Lequesne Index values during follow-up visits exhibited a decrease, signifying improvement in the clinical condition. Notably, scores were significantly more favorable with the 30 mg of HA injection compared to the 60 mg of HA injection.

Conclusion

This study suggests that the triple low-dose injection of HMW HA is more effective in improving WOMAC, VAS scores and Lequesne Index values than a single high-dose injection.
Impact of vitamin D supplementation on the clinical outcomes of COVID-19 pneumonia patients: a single-center randomized controlled trial
Authors: Dilokpattanamongkol Pitchaya , Yan Chadakan , Jayanama Kulapong , Ngamjanyaporn Pintip , Sungkanuparph Somnuek , Rotjanapan Porpon
Published: February 2024

Background

Vitamin D supplementation for infectious diseases has been discussed, but its role in COVID-19 is unclear. Therefore, this study examined the clinical outcomes of COVID-19 pneumonia patients who received vitamin D supplementation.

Methods

This prospective, open-label, randomized controlled trial was conducted in a university hospital between July 2020 and March 2022. The inclusion criteria were patients aged ≥ 18 years with COVID-19 pneumonia patients. The patients were randomized into two groups: an intervention group receiving vitamin D supplementation (alfacalcidol, two mcg orally daily) until discharge and a control group. The clinical outcomes were pneumonia treatment duration, length of hospital stay, and change in pneumonia severity index between enrollment and discharge. Subgroup analysis was conducted for supplemental oxygen use, high-dose corticosteroid administration, evidence of lymphopenia, C-reactive protein concentration, and total serum vitamin D concentration. Adverse events were monitored.

Results

Two hundred ninety-four patients were recruited (147 per group). The two groups did not differ in pneumonia treatment duration to discharge (p = 0.788) or length of hospital stay (p = 0.614). The reduction in the pneumonia severity index between enrollment and discharge was more significant in the intervention group (p = 0.007); a significant decrease was also observed among patients who had C-reactive protein > 30 mg/L (p < 0.001). No adverse reactions were recorded.

Conclusions

Adding active vitamin D to standard treatment may benefit COVID-19 pneumonia patients who require supplemental oxygen or high-dose corticosteroid therapy or who have high C-reactive protein concentrations (> 30 mg/L) upon treatment initiation.

Trial registration

Thai Clinical Trials Registry TCTR20210906005 (retrospectively registered, 6 September 2021).
Prenatal detection and molecular cytogenetic characterization of Xp deletion and Xq duplication: a case report and literature review
Authors: Lin Qing , Liang Chunya , Du Bole , Li Lijiao , Li Hong , Mai Xiaolan , Li Sheng , Xu Wenyu , Wu Cunzhen , Zeng Mi
Published: February 2024

Background

Copy number variation (CNV) of X chromosome can lead to a variety of neonatal abnormalities, especially for male fetuses. In recent years, due to the high sensitivity and high specificity of NIPS, its application has gradually expanded from chromosome aneuploidy to CNV. Few prenatal cases involving the detection of Xq duplication and deletion by NIPS have been reported, but it is of great significance for genetic counseling.

Case presentation

A 36-year-old woman was referred for prenatal diagnosis and genetic counseling at 17 weeks of gestation because of abnormal result of noninvasive prenatal screening (NIPS). Multiple congenital malformations, hydrocephalus, and enlarged gallbladder were observed by prenatal ultrasound. Amniocentesis revealed the karyotype of the fetus as 46, XN, add(X) (p22.2) and the result of chromosomal microarray analysis was arr[hg19] Xq27.1q28(138,506,454–154896094) × 2 and arr[hg19] Xp22.33p22.32(168,551–5,616,964) × 1. CNV-seq showed that the mother shares a 16.42 Mb duplication in the Xq27.1-q28 region and a 2.97 Mb deletion in the Xp22.33-p22.32 region. After genetic counseling, the couple chose to terminate the pregnancy.

Conclusion

The combination of NIPS and CMA would be of values in detection of subchromosomal duplications and/or deletions at fetal stage. The detection of X chromosome aberration in a male fetus should give suspicion of the possibility of maternal inheritance.
Proteome-wide mendelian randomization investigates potential associations in heart failure and its etiology: emphasis on PCSK9
Authors: Lin Lichao , Yu Huizhen , Xue Yan , Wang Liman , Zhu Pengli
Published: February 2024

Background

Heart failure (HF) is a prevalent clinical syndrome with diverse etiologies. It is crucial to identify novel therapeutic targets based on underlying causes. Here, we aimed to use proteome-wide Mendelian randomization (MR) analyses to identify the associations between genetically predicted elevated levels of circulating proteins and distinct HF outcomes, along with specific HF etiologies.

Methods

Protein quantitative trait loci (pQTL) data for circulating proteins were sourced from the Atherosclerosis Risk in Communities (ARIC) study, encompassing 7,213 individuals and profiling 4,657 circulating proteins. Genetic associations for outcomes were obtained from the HERMES Consortium and the FinnGen Consortium. Colocalization analysis was employed to assess the impact of linkage disequilibrium on discovered relationships. For replication, two-sample MR was conducted utilizing independent pQTL data from the deCODE study. Multivariable MR (MVMR) and two-step MR were further conducted to investigate potential mediators.

Results

Two proteins (PCSK9 and AIDA) exhibited associations with HF in patients with coronary heart disease (CHD), and four proteins (PCSK9, SWAP70, NCF1, and RELT) were related with HF in patients receiving antihypertensive medication. Among these associations, strong evidence from subsequent analyses supported the positive relationship between genetically predicted PCSK9 levels and the risk of HF in the context of CHD. Notably, MVMR analysis revealed that CHD and LDL-C did not exert a complete mediating effect in this relationship. Moreover, two-step MR results yielded valuable insights into the potential mediating proportions of CHD or LDL-C in this relationship.

Conclusions

Our findings provide robust evidence supporting the association between PCSK9 and concomitant HF and CHD. This association is partly elucidated by the influence of CHD or LDL-C, underscoring the imperative for additional validation of this connection and a thorough exploration of the mechanisms through which PCSK9 directly impacts ischemic HF.
lncRNA-MIAT rs9625066 polymorphism could be a potential biomarker for ischemic stroke
Authors: Weng Yin-Hua , Chen Jie , Yu Wen-Tao , Luo Yan-Ping , Liu Chao , Yang Jun , Liu Hong-Bo
Published: February 2024

Background

Ischemic stroke (IS) is a common and serious neurological condition that is highly fatal but so far no early diagnostic markers are available. Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA) that could lead to IS by inducing autophagy and apoptosis in neuronal cells. However, there has been no report on the link between susceptibility to IS and the single-nucleotide polymorphisms (SNPs) of MIAT. This study aimed to investigate the association between MIAT gene polymorphisms and IS risk.

Methods

A total of 320 IS patients and 310 age-, sex- and race-matched controls were included in this study. Four polymorphisms (rs2157598, rs5761664, rs1894720, and rs9625066) were genotyped by using SNPscan technique.

Results

Among the 4 polymorphisms of MIAT, only rs9625066 was associated with IS risk (CA vs. CC: adjusted OR = 0.55, 95% CI, 0.37–0.85, P = 0.006; AA vs. CC: adjusted OR = 0.39, 95% CI, 0.16–0.94, P = 0.036; (AA + CA vs. CC: adjusted OR = 0.53, 95% CI, 0.35–0.80, P = 0.002; A vs. C adjusted OR = 0.59, 95% CI, 0.42–0.82, P = 0.002). Haplotype analysis showed a 1.32-fold increase (95% CI, 1.05–1.67, P = 0.017) in IS risk for rs2157598-rs5761664-rs1894720-rs9625066 (A-C-G-C). Logistic regression analysis identified some independent impact factors for IS including rs9625066 AA/AC, TC, TG, HDL-C (P < 0.05).

Conclusion

The rs9625066 polymorphism of MIAT might be associated with IS susceptibility in Chinese population, in which AA/CA plays a protective role in IS, whereas the CC genotype increases the risk of developing IS, suggesting it might be a marker predictive of IS risk.
Impact of preexisting interstitial lung disease on mortality in COVID-19 patients from the early pandemic to the delta variant epidemic: a nationwide population-based study
Authors: Miyashita Koichi , Hozumi Hironao , Furuhashi Kazuki , Nakatani Eiji , Inoue Yusuke , Yasui Hideki , Suzuki Yuzo , Karayama Masato , Enomoto Noriyuki , Fujisawa Tomoyuki , Inui Naoki , Ojima Toshiyuki , Suda Takafumi
Published: February 2024

Background

COVID-19 patients with preexisting interstitial lung disease (ILD) were reported to have a high mortality rate; however, this was based on data from the early stages of the pandemic. It is uncertain how their mortality rates have changed with the emergence of new variants of concern as well as the development of COVID-19 vaccines and treatments. It is also unclear whether having ILD still poses a risk factor for mortality. As COVID-19 continues to be a major concern, further research on COVID-19 patients with preexisting ILD is necessary.

Methods

We extracted data on COVID-19 patients between January 2020–August 2021 from a Japanese nationwide insurance claims database and divided them into those with and without preexisting ILD. We investigated all-cause mortality of COVID-19 patients with preexisting ILD in wild-type-, alpha-, and delta-predominant waves, to determine whether preexisting ILD was associated with increased mortality.

Results

Of the 937,758 adult COVID-19 patients, 7,333 (0.8%) had preexisting ILD. The proportion of all COVID-19 patients who had preexisting ILD in the wild-type-, alpha-, and delta-predominant waves was 1.2%, 0.8%, and 0.3%, respectively, and their 60-day mortality was 16.0%, 14.6%, and 7.5%, respectively. The 60-day mortality significantly decreased from the alpha-predominant to delta-predominant waves (difference − 7.1%, 95% confidence intervals (CI) − 9.3% to − 4.9%). In multivariable analysis, preexisting ILD was independently associated with increased mortality in all waves with the wild-type-predominant, odds ratio (OR) 2.10, 95% CI 1.91–2.30, the alpha-predominant wave, OR 2.14, 95% CI 1.84–2.50, and the delta-predominant wave, OR 2.10, 95%CI 1.66–2.66.

Conclusions

All-cause mortality rates for COVID-19 patients with preexisting ILD decreased from the wild-type- to the more recent delta-predominant waves. However, these patients were consistently at higher mortality risk than those without preexisting ILD. We emphasize that careful attention should be given to patients with preexisting ILD despite the change in the COVID-19 environment.
Trend analysis of malaria surveillance data in West Wallaga, West Oromia, Ethiopia: a framework for planning and elimination
Authors: Tesfaye Sahilu , Yesuf Aman
Published: February 2024

Background

Although Ethiopia has made a remarkable progress towards malaria prevention and control, malaria remains one of the most devastating parasitic diseases affecting humans. However, the distribution and transmission of malaria varies across the country. The study aimed to describe 5 years of malaria distribution and magnitude within the West Wallaga Zone and its respective woredas.

Methods

A retrospective cross-sectional study design was conducted from April 10, 2019 to May 2019. Surveillance data collected weekly for a 5-year (2014–2018) from health facilities and private clinics that were archived in zonal PHEM database were reviewed. The checklist contained variety of variables was developed to collect data. Descriptive analysis was conducted to determine the proportion ofPlasmodiumspecies, positivity rate, mortality and fatality rate, time trend, and admission status; and presented by text, tables and figures.

Results

Of the total of 588,119 suspected malaria cases, 78,658 (43/1000 populations) were positive with average positivity rate of 13.4%. Among confirmed cases, 59,794 (75%) of cases were attributed toPlasmodium falciparum, 16,518 (20%) werePlasmodium vivax,and 2,360 (5%) were mixed infections. The maximum (145,091) and minimum (74,420) transmissions were reported in 2014 and 2018, respectively. There was seasonal variation in transmission; spring (from May to July) and also autumn seasons (from October to November) were found as malaria transmission peaks. Although incidence rate declined throughout the study period, the average annual incidence rate was 14.38 per 1000 populations. The average case fatality rate of 5 consecutive years was 12/78,658 (15/100,000) population.

Conclusion

Although the malaria prevalence was decreased, the mortality due to malaria was increased in the 5-year study period, and malaria is still among the major public health problems. The dominant species of malaria parasites wereP. falciparumandP. vivax.Attention is needed in scaling-up vector control tools in high malaria transmission periods.
A community challenge to predict clinical outcomes after immune checkpoint blockade in non-small cell lung cancer
Authors: Mason Mike , Lapuente-Santana Óscar , Halkola Anni S. , Wang Wenyu , Mall Raghvendra , Xiao Xu , Kaufman Jacob , Fu Jingxin , Pfeil Jacob , Banerjee Jineta , Chung Verena , Chang Han , Chasalow Scott D. , Lin Hung Ying , Chai Rongrong , Yu Thomas , Finotello Francesca , Mirtti Tuomas , Mäyränpää Mikko I. , Bao Jie , Verschuren Emmy W. , Ahmed Eiman I. , Ceccarelli Michele , Miller Lance D. , Monaco Gianni , Hendrickx Wouter R. L. , Sherif Shimaa , Yang Lin , Tang Ming , Gu Shengqing Stan , Zhang Wubing , Zhang Yi , Zeng Zexian , Das Sahu Avinash , Liu Yang , Yang Wenxian , Bedognetti Davide , Tang Jing , Eduati Federica , Laajala Teemu D. , Geese William J. , Guinney Justin , Szustakowski Joseph D. , Vincent Benjamin G. , Carbone David P.
Published: February 2024

Background

Predictive biomarkers of immune checkpoint inhibitor (ICI) efficacy are currently lacking for non-small cell lung cancer (NSCLC). Here, we describe the results from the Anti–PD-1 Response Prediction DREAM Challenge, a crowdsourced initiative that enabled the assessment of predictive models by using data from two randomized controlled clinical trials (RCTs) of ICIs in first-line metastatic NSCLC.

Methods

Participants developed and trained models using public resources. These were evaluated with data from the CheckMate 026 trial (NCT02041533), according to the model-to-data paradigm to maintain patient confidentiality. The generalizability of the models with the best predictive performance was assessed using data from the CheckMate 227 trial (NCT02477826). Both trials were phase III RCTs with a chemotherapy control arm, which supported the differentiation between predictive and prognostic models. Isolated model containers were evaluated using a bespoke strategy that considered the challenges of handling transcriptome data from clinical trials.

Results

A total of 59 teams participated, with 417 models submitted. Multiple predictive models, as opposed to a prognostic model, were generated for predicting overall survival, progression-free survival, and progressive disease status with ICIs. Variables within the models submitted by participants included tumor mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, and gene-expression–based signatures. The best-performing models showed improved predictive power over reference variables, including TMB or PD-L1.

Conclusions

This DREAM Challenge is the first successful attempt to use protected phase III clinical data for a crowdsourced effort towards generating predictive models for ICI clinical outcomes and could serve as a blueprint for similar efforts in other tumor types and disease states, setting a benchmark for future studies aiming to identify biomarkers predictive of ICI efficacy.

Trial registration: CheckMate 026; NCT02041533, registered January 22, 2014.

CheckMate 227; NCT02477826, registered June 23, 2015.
Senescent fibroblast facilitates re-epithelization and collagen deposition in radiation-induced skin injury through IL-33-mediated macrophage polarization
Authors: Chen Yan , Ma Le , Cheng Zhuo , Hu Zhihe , Xu Yang , Wu Jie , Dai Yali , Shi Chunmeng
Published: February 2024

Background

The need for radiotherapy among the elderly rises with increasing life expectancy and a corresponding increase of elderly cancer patients. Radiation-induced skin injury is one of the most frequent adverse effects in radiotherapy patients, severely limiting their life quality. Re-epithelialization and collagen deposition have essential roles in the recovery of skin injuries induced by high doses of ionizing radiation. At the same time, radiation-induced senescent cells accumulate in irradiated tissues. However, the effects and mechanisms of senescent cells on re-epithelialization and collagen deposition in radiation-induced skin injury have not been fully elucidated.

Results

Here, we identified a role for a population of senescent cells expressing p16 in promoting re-epithelialization and collagen deposition in radiation-induced skin injury. Targeted ablation of p16+ senescent cells or treatment with Senolytics resulted in the disruption of collagen structure and the retardation of epidermal coverage. By analyzing a publicly available single-cell sequencing dataset, we identified fibroblasts as a major contributor to the promotion of re-epithelialization and collagen deposition in senescent cells. Notably, our analysis of publicly available transcriptome sequencing data highlighted IL-33 as a key senescence-associated secretory phenotype produced by senescent fibroblasts. Neutralizing IL-33 significantly impedes the healing process. Finally, we found that the effect of IL-33 was partly due to the modulation of macrophage polarization.

Conclusions

In conclusion, our data suggested that senescent fibroblasts accumulated in radiation-induced skin injury sites participated in wound healing mainly by secreting IL-33. This secretion regulated the local immune microenvironment and macrophage polarization, thus emphasizing the importance of precise regulation of senescent cells in a phased manner.

Graphical Abstract
Combined therapy of CAR-IL-15/IL-15Rα-T cells and GLIPR1 knockdown in cancer cells enhanced anti-tumor effect against gastric cancer
Authors: Ye Jianbin , Liu Qiaoyuan , He Yunxuan , Song Zhenkun , Lin Bao , Hu Zhiwei , Hu Juanyuan , Ning Yunshan , Cai Cheguo , Li Yan
Published: February 2024

Background

Chimeric antigen receptor (CAR) T cell therapy has shown remarkable responses in hematological malignancies with several approved products, but not in solid tumors. Patients suffer from limited response and tumor relapse due to low efficacy of CAR-T cells in the complicated and immunosuppressive tumor microenvironment. This clinical challenge has called for better CAR designs and combined strategies to improve CAR-T cell therapy against tumor changes.

Methods

In this study, IL-15/IL-15Rα was inserted into the extracellular region of CAR targeting mesothelin. In-vitro cytotoxicity and cytokine production were detected by bioluminescence-based killing and ELISA respectively. In-vivo xenograft mice model was used to evaluate the anti-tumor effect of CAR-T cells. RNA-sequencing and online database analysis were used to identify new targets in residual gastric cancer cells after cytotoxicity assay. CAR-T cell functions were detected in vitro and in vivo after GLI Pathogenesis Related 1 (GLIPR1) knockdown in gastric cancer cells. Cell proliferation and migration of gastric cancer cells were detected by CCK-8 and scratch assay respectively after GLIPR1 were overexpressed or down-regulated.

Results

CAR-T cells constructed with IL-15/IL-15Rα (CAR-ss-T) showed significantly improved CAR-T cell expansion, cytokine production and cytotoxicity, and resulted in superior tumor control compared to conventional CAR-T cells in gastric cancer. GLIPR1 was up-regulated after CAR-T treatment and survival was decreased in gastric cancer patients with high GLIPR1 expression. Overexpression of GLIPR1 inhibited cytotoxicity of conventional CAR-T but not CAR-ss-T cells. CAR-T treatment combined with GLIPR1 knockdown increased anti-tumor efficacy in vitro and in vivo.

Conclusions

Our data demonstrated for the first time that this CAR structure design combined with GLIPR1 knockdown in gastric cancer improved CAR-T cell-mediated anti-tumor response.
Autoinducer-2 promotes the colonization of Lactobacillus rhamnosus GG to improve the intestinal barrier function in a neonatal mouse model of antibiotic-induced intestinal dysbiosis
Authors: Hu Riqiang , Yang Ting , Ai Qing , Shi Yuan , Ji Yanchun , Sun Qian , Tong Bei , Chen Jie , Wang Zhengli
Published: February 2024

Background

Human health is seriously threatened by antibiotic-induced intestinal disorders. Herein, we aimed to determine the effects of Autoinducer-2 (AI-2) combined with Lactobacillus rhamnosus GG (LGG) on the intestinal barrier function of antibiotic-induced intestinal dysbiosis neonatal mice.

Methods

An antibiotic-induced intestinal dysbiosis neonatal mouse model was created using antibiotic cocktails, and the model mice were randomized into the control, AI-2, LGG, and LGG + AI-2 groups. Intestinal short-chain fatty acids and AI-2 concentrations were detected by mass spectrometry and chemiluminescence, respectively. The community composition of the gut microbiota was analyzed using 16S rDNA sequencing, and biofilm thickness and bacterial adhesion in the colon were assessed using scanning electron microscopy. Transcriptome RNA sequencing of intestinal tissues was performed, and the mRNA and protein levels of HCAR2 (hydroxycarboxylic acid receptor 2), claudin3, and claudin4 in intestinal tissues were determined using quantitative real-time reverse transcription PCR and western blotting. The levels of inflammatory factors in intestinal tissues were evaluated using enzyme-linked immunosorbent assays (ELISAs). D-ribose, an inhibitor of AI-2, was used to treat Caco-2 cells in vitro.

Results

Compared with the control, AI-2, and LGG groups, the LGG + AI-2 group showed increased levels of intestinal AI-2 and proportions of Firmicutes and Lacticaseibacillus, but a reduced fraction of Proteobacteria. Specifically, the LGG + AI-2 group had considerably more biofilms and LGG on the colon surface than those of other three groups. Meanwhile, the combination of AI-2 and LGG markedly increased the concentration of butyric acid and promoted Hcar2, claudin3 and claudin4 expression levels compared with supplementation with LGG or AI-2 alone. The ELISAs revealed a significantly higher tumor necrosis factor alpha (TNF-α) level in the control group than in the LGG and LGG + AI-2 groups, whereas the interleukin 10 (IL-10) level was significantly higher in the LGG + AI-2 group than in the other three groups. In vitro, D-ribose treatment dramatically suppressed the increased levels of Hcar2, claudin3, and claudin4 in Caco-2 cells induced by AI-2 + LGG.

Conclusions

AI-2 promotes the colonization of LGG and biofilm formation to improve intestinal barrier function in an antibiotic-induced intestinal dysbiosis neonatal mouse model.
The innovative checkpoint inhibitors of lung adenocarcinoma, cg09897064 methylation and ZBP1 expression reduction, have implications for macrophage polarization and tumor growth in lung cancer
Authors: Wang Ailing , Zheng Wei-sha , Luo Zhen , Bai Lian , Zhang Shi
Published: February 2024

Lung cancer, a prevalent and aggressive disease, is characterized by recurrence and drug resistance. It is essential to comprehend the fundamental processes and discover novel therapeutic objectives for augmenting treatment results. Based on our research findings, we have identified a correlation between methylation of cg09897064 and decreased expression of ZBP1, indicating a link to unfavorable prognosis in patients with lung cancer. Furthermore, these factors play a role in macrophage polarization, with ZBP1 upregulated in M1 macrophages compared to both M0 and M2 polarized macrophages. We observed cg09897064 methylation in M2 polarization, but not in M0 and M1 polarized macrophages. ATACseq analysis revealed closed chromatin accessibility of ZBP1 in M0 polarized macrophages, while open accessibility was observed in both M1 and M2 polarized macrophages. Our findings suggest that ZBP1 is downregulated in M0 polarized macrophages due to closed chromatin accessibility and downregulated in M2 polarized macrophages due to cg09897064 methylation. Further investigations manipulating cg09897064 methylation and ZBP1 expression through overexpression plasmids and shRNAs provided evidence for their role in modulating macrophage polarization and tumor growth. ZBP1 inhibits M2 polarization and suppresses tumor growth, while cg09897064 methylation promotes M2 polarization and macrophage-induced tumor growth. In mechanism investigations, we found that cg09897064 methylation impairs CEBPA binding to the ZBP1 promoter, leading to decreased ZBP1 expression. Clinical experiments were conducted to validate the correlation between methylation at cg09897064, ZBP1 expression, and macrophage M2 polarization. Targeting these factors may hold promise as a strategy for developing innovative checkpoint inhibitors in lung cancer treatment.
Integration of National Health Insurance claims data and animal models reveals fexofenadine as a promising repurposed drug for Parkinson’s disease
Authors: Kim Jae-Bong , Kim Yujeong , Kim Soo-Jeong , Ha Tae‑Young , Kim Dong-Kyu , Kim Dong Won , So Minyoung , Kim Seung Ho , Woo Hyun Goo , Yoon Dukyong , Park Sang Myun
Published: February 2024

Background

Parkinson’s disease (PD) is a common and costly progressive neurodegenerative disease of unclear etiology. A disease-modifying approach that can directly stop or slow its progression remains a major unmet need in the treatment of PD. A clinical pharmacology-based drug repositioning strategy is a useful approach for identifying new drugs for PD.

Methods

We analyzed claims data obtained from the National Health Insurance Service (NHIS), which covers a significant portion of the South Korean population, to investigate the association between antihistamines, a class of drugs commonly used to treat allergic symptoms by blocking H1 receptor, and PD in a real-world setting. Additionally, we validated this model using various animal models of PD such as the 6-hydroxydopmaine (6-OHDA), α-synuclein preformed fibrils (PFF) injection, and Caenorhabditis elegans (C. elegans) models. Finally, whole transcriptome data and Ingenuity Pathway Analysis (IPA) were used to elucidate drug mechanism pathways.

Results

We identified fexofenadine as the most promising candidate using National Health Insurance claims data in the real world. In several animal models, including the 6-OHDA, PFF injection, and C. elegans models, fexofenadine ameliorated PD-related pathologies. RNA-seq analysis and the subsequent experiments suggested that fexofenadine is effective in PD via inhibition of peripheral immune cell infiltration into the brain.

Conclusion

Fexofenadine shows promise for the treatment of PD, identified through clinical data and validated in diverse animal models. This combined clinical and preclinical approach offers valuable insights for developing novel PD therapeutics.
Mapping study for health emergency and disaster risk management competencies and curricula: literature review and cross-sectional survey
Authors: Hung Kevin K. C. , MacDermot Makiko K. , Hui Theresa S. I. , Chan Suet Yi , Mashino Sonoe , Mok Catherine P. Y. , Leung Pak Ho , Kayano Ryoma , Abrahams Jonathan , Wong Chi Shing , Chan Emily Y. Y. , Graham Colin A.
Published: February 2024

Background

With the increasing threat of hazardous events at local, national, and global levels, an effective workforce for health emergency and disaster risk management (Health EDRM) in local, national, and international communities is urgently needed. However, there are no universally accepted competencies and curricula for Health EDRM. This study aimed to identify Health EDRM competencies and curricula worldwide using literature reviews and a cross-sectional survey.

Methods

Literature reviews in English and Japanese languages were performed. We searched MEDLINE, EMBASE, CINAHL (English), and the ICHUSHI (Japanese) databases for journal articles published between 1990 and 2020. Subsequently, a cross-sectional survey was sent to WHO Health EDRM Research Network members and other recommended experts in October 2021 to identify competency models and curricula not specified in the literature search.

Results

Nineteen studies from the searches were found to be relevant to Health EDRM competencies and curricula. Most of the competency models and curricula were from the US. The domains included knowledge and skills, emergency response systems (including incident management principles), communications, critical thinking, ethical and legal aspects, and managerial and leadership skills. The cross-sectional survey received 65 responses with an estimated response rate of 25%. Twenty-one competency models and 20 curricula for managers and frontline personnel were analyzed; managers' decision-making and leadership skills were considered essential.

Conclusion

An increased focus on decision-making and leadership skills should be included in Health EDRM competencies and curricula to strengthen the health workforce.