bluuebunny/crossref_metadata_2025 huggingface dataset:
Time trend of pancreatic cancer mortality in the Western Pacific Region: age-period-cohort analysis from 1990 to 2019 and forecasting for 2044
Authors: Jiang Wenkai , Xiang Caifei , Du Yan , Li Xiao , Li Xin , Zhou Wence
Published: September 2023

Background

Pancreatic cancer poses a serious medical problem worldwide. Countries in the Western Pacific Region are facing public health challenges from cancer. This study assesses the time trends of pancreatic cancer mortality in the Western Pacific Region from 1990 to 2019 and predicts its trend to 2044.

Methods

Mortality data were obtained from the Global Health Data Exchange. We used an age-period-cohort model to estimate age, period and birth cohort effects on pancreatic cancer mortality from 1990 to 2019 by calculating net drift, local drift, age-specific rate, period rate ratio, and cohort rate ratio. We also predict pancreatic cancer mortality to 2044 in Western Pacific countries.

Results

Overall, there were 178,276 (95% uncertain interval: 157,771 to 198,636) pancreatic cancer deaths in the Western Pacific Region in 2019, accounting for 33.6% of all deaths due to pancreatic cancer worldwide. There were significant increases in pancreatic cancer disability-adjusted life years between 1990 and 2019 in the Western Pacific Region, mainly due to population growth and aging. Pancreatic cancer mortality increased with age. The period effect showed an increasing trend of mortality for both sexes over the study period. Compared to the reference period (2000 to 2004), the rate ratio was elevated in both males and females in the period of 2015 to 2019. There was an overall increasing rate ratio from early birth cohorts to recent cohorts. Deaths may continue to increase in the next 25 years in the ten countries, while most countries have seen their age-standardized rate forecasts fall.

Conclusion

The mortality of pancreatic cancer is still high in the Western Pacific Region. Countries/territories should focus on pancreatic cancer prevention and early cancer screening in high-risk populations. Specific public health methods and policies aimed at reducing risk factors for pancreatic cancer are also needed.
Development and validation of a risk model with variables related to non-small cell lung cancer in patients with pulmonary nodules: a retrospective study
Authors: Liao Zufang , Zheng Rongjiong , Li Ni , Shao Guofeng
Published: September 2023

Background

Lung cancer is a major global threat to public health for which a novel predictive nomogram is urgently needed. Non-small cell lung cancer (NSCLC) which accounts for the main port of lung cancer cases is attracting more and more people’s attention.

Patients and methods

Here, we designed a novel predictive nomogram using a design dataset consisting of 515 pulmonary nodules, with external validation being performed using a separate dataset consisting of 140 nodules and a separate dataset consisting of 237 nodules. The selection of significant variables for inclusion in this model was achieved using a least absolute shrinkage and selection operator (LASSO) logistic regression model, after which a corresponding nomogram was developed. C-index values, calibration plots, and decision curve analyses were used to gauge the discrimination, calibration, and clinical utility, respectively, of this predictive model. Validation was then performed with the internal bootstrapping validation and external cohorts.

Results

A predictive nomogram was successfully constructed incorporating hypertension status, plasma fibrinogen levels, blood urea nitrogen (BUN), density, ground-glass opacity (GGO), and pulmonary nodule size as significant variables associated with nodule status. This model exhibited good discriminative ability, with a C-index value of 0.765 (95% CI: 0.722-0.808), and was well-calibrated. In validation analyses, this model yielded C-index values of 0.892 (95% CI: 0.844-0.940) for external cohort and 0.853 (95% CI: 0.807-0.899) for external cohort 2. In the internal bootstrapping validation, C-index value could still reach 0.753. Decision curve analyses supported the clinical value of this predictive nomogram when used at a NSCLC possibility threshold of 18%.

Conclusion

The nomogram constructed in this study, which incorporates hypertension status, plasma fibrinogen levels, BUN, density, GGO status, and pulmonary nodule size, was able to reliably predict NSCLC risk in this Chinese cohort of patients presenting with pulmonary nodules.
Improved clinical outcomes in advanced hepatocellular carcinoma treated with transarterial chemoembolization plus atezolizumab and bevacizumab: a bicentric retrospective study
Authors: Cao Fei , Shi Changsheng , Zhang Guofu , Luo Jun , Zheng Jiaping , Hao Weiyuan
Published: September 2023

Purpose

The aim of the present study was to assess the efficacy and safety of transarterial chemoembolization (TACE) combined with atezolizumab and bevacizumab (hereafter, TACE-Atez/Bev) in the treatment of advanced hepatocellular carcinoma (HCC) patients.

Materials and methods

Clinical information was collected from consecutive patients with advanced HCC who received treatment with TACE-Atez/Bev or Atez/Bev from April 2021 and October 2022. Treatment response, overall survival (OS), and progression-free survival (PFS) were the primary outcomes of this study. Adverse events (AEs) were the secondary outcomes. Propensity score matching (PSM) analysis was applied to reduce bias between two groups.

Results

This study included 62 patients in the TACE-Atez/Bev group and 77 patients in the Atez/Bev group. The objective response rate (ORR) of the TACE-Atez/Bev group and the Atez/Bev group were 38.7% and 16.9% (P=0.004). However, there was no statistical difference in disease control rate between the two groups (69.4% vs 63.6%, P=0.479). Before PSM, the median OS was 14 months in the TACE-Atez/Bev group and 10 months in the Atez/Bev group (P=0.014). The median PFS in the TACE-Atez/Bev and Atez/Bev groups was 10 months and 6 months, respectively (P=0.001). After PSM, the median OS in the two groups was 14 months and 9 months, respectively (P=0.01). The median PFS was 7 months and 6 months, respectively (P=0.036). Multivariable analysis showed that treatment method was independent prognostic factors affecting OS.

Conclusions

Compared with Atez/Bev treatment, TACE-Atez/Bev showed better OS, PFS, and ORR for Chinese patients with advanced HCC, with an acceptable safety profile.
Real-world treatment patterns and economic burden of post-cataract macular edema
Authors: Ahmadyar Gina , Carlson Josh J. , Kimura Alan , Alobaidi Ali , Hallak Joelle , Hansen Ryan N.
Published: September 2023

Background

Post-cataract macular edema (PCME) is a condition that can occur in patients following cataract surgery without risk factors and complications. Although 80% of patients experience spontaneous resolution after 3 to 12 months, in persistent cases, it can lead to permanent vision loss if left untreated. There are currently no standardized treatment guidelines for PCME, and there have been limited studies showing the impact of PCME on annual Medicare spending and ophthalmology-related outpatient visits per case compared to those without the complication. This study aims to evaluate real-world treatment patterns and the economic burden of patients with PCME.

Methods

This retrospective claims analysis identified patients from the IBM® MarketScan® Commercial and Medicare Supplemental databases. Patients with (n = 2430) and without (n = 7290) PCME 1 year post cataract surgery were propensity score matched 1:3 based on age, geographic region, diabetes presence, cataract surgery type, and Charlson Comorbidity Index. Treatment pattern analysis for each PCME patient summarized the distribution of medications across lines of therapy. Economic burden analysis compared the mean number and costs of eye-related outpatient visits, optical coherence tomography imaging scans, and ophthalmic medications between the 2 groups using linear regression models.

Results

Treatment pattern analysis found 27 different treatment combinations across 6 treatment lines. The most common first-line treatments were topical steroid drops (372 [30%]), topical nonsteroidal anti-inflammatory drug drops (321 [27%]), and intraocular or periocular injectable steroids (189 [15%]). Compared to match controls, PCME patients averaged 6 additional eye-related outpatient office visits (95% CI: 5.7–6.2) resulting in an additional $3,897 (95% CI: $3,475 - $4,319) in total costs. Patients filled 3 more ophthalmology-related outpatient prescription medications (95% CI: 2.8–3.2), adding $371 in total cost (95% CI: $332 – $410).

Conclusions

PCME treatment patterns showed wide clinical variability in treatments and time, specifically regarding injectable treatments and combination therapy. Additionally, significantly higher healthcare resource use and economic burden were found for both patients and payers when comparing PCME patients to non-PMCE controls. These results highlight the need for treatment standardization and demonstrate that interventions targeted at preventing PCME may be valuable.
Comprehensive evaluation of functional vision, quality of life, and cognitive ability in pediatric uveitis
Authors: Wan Wenjuan , Chen Zhijun , Xun Yan , Yi Kun , Zhu Ying , Pu Yanlin , Su Guannan , Zhou Chunjiang , Wang Yao , Yang Peizeng
Published: September 2023

Background

Pediatric uveitis may cause severe impairment of vision in children and affect their quality of life as well as cognitive ability. This study aims to evaluate the functional vision, visual-related and health-related quality of life, and cognitive ability in pediatric uveitis.

Methods

Children with uveitis aged 5–16 years old completed six validated instruments to assess functional visual ability with Cardiff Visual Ability Questionnaire for Children (CVAQC), vision-related quality of life with Impact of Vision Impairment for Children (IVI-C), health-related quality of life with Pediatric Quality of Life Inventory (PedsQL), cognitive ability with Chinese Wechsler Intelligence Scale for Children (C-WISC), and depression and anxiety evaluation with Hospital Anxiety and Depression Scale (HAD).

Results

The CVAQC, IVI-C, and PedsQL scores of pediatric uveitis were significantly lower than that of normal levels. Full-scale intelligence quotient (IQ) and performance IQ were significantly lower in pediatric uveitis patients with impaired vision in their best eye (visual acuity < 0.3) compared to those with a vision equal to or better than 0.3. Verbal IQ was significantly lower in male pediatric uveitis patients with impaired vision compared to those with a vision equal to or better than 0.3. Additionally, parents of pediatric uveitis patients with impaired vision generally had lower educational levels than parents of those with a vision equal to or better than 0.3.

Conclusions

Impaired vision caused by pediatric uveitis has a significant impact on children’s functional visual ability and quality of life. The development of cognitive function in pediatric uveitis is also significantly hindered.
Choroid vascular changes in hyperopic anisometropia amblyopia using SS-OCTA
Authors: Cao Yiwen , Zhang Yadi , Gu Xiaopeng , Zhu Dehai , Yang Liu
Published: September 2023

Purpose

To observe and understand the structural changes in choroidal vessels in eyes with hyperopic anisometropic amblyopia using swept-source optical coherence tomography angiography (SS-OCTA).

Methods

A total of 44 patients were enrolled in this study: 22 children with hyperopic anisometropic amblyopia and 22 age-matched controls. SS-OCTA was used to scan the 6*6 mm macular area of their eyes. The average choroidal thickness (CT) and choroidal capillary flow area (CC) in a 3 mm diameter area centered on the macular area were obtained. The choroidal vascularity volume (CVV) was automatically extracted and 3D reconstructed by inbuild software, and the three-dimensional choroidal vascularity index (3D-CVI) was calculated. The effect of amblyopia on the choroidal vessel structure was assessed using generalized linear estimating equations (GEEs) corrected for axial length, sex, age, and best-corrected visual acuity.

Results

The CC was greater in amblyopic eyes than in fellow eyes (P = 0.014) but was not significantly different from that in control eyes (P = 0.963). After correcting for sex, age, axial length, and visual acuity using GEEs, the mean CT in the amblyopic eyes was greater than that in the fellow eyes (P = 0.030) but was not significantly different from that in the control eyes (P = 0.160). The 3D-CVI in amblyopic eyes was higher than that in control eyes (P = 0.038) but was not significantly different from that in fellow eyes (P = 0.407). The three-dimensional choroidal vascularity volume (3D-CVV) was higher in amblyopic eyes than in fellow eyes (P = 0.046) and control eyes (P = 0.023).

Conclusions

We found that eyes with hyperopic anisometropic amblyopia demonstrated higher CT, CC and 3D-CVV values than the contralateral eyes after correction, while the 3D-CVI was unchanged. Compared with control eyes, amblyopic eyes had higher 3D-CVV and 3D-CVI values but similar CT and CC values. Amblyopic eyes may have different choroidal vascular structures from fellow and control eyes.
Dietary acid load, depression, and anxiety: results of a population-based study
Authors: Bahari Hossein , Seifi Najmeh , Foroumandi Elahe , Kourepaz Fatemeh , Shahabi Hediye Erfaniyan , Ervin Kimia , Khabari Nahid , Ferns Gordon A. , Ghayour-Mobarhan Majid
Published: September 2023

Background

Dietary acid load seems to be associated with psychological disorders through several mechanisms, and may barricade their treatment and recovery. The aim of current study was to evaluate the relationship between dietary acid load, using potential renal acid load (PRAL) and dietary acid load (DAL) scores, with the severity of depression and anxiety among Iranian adults.

Methods

A total of 6531 participants aged 35–65 years were recruited in this cross-sectional study. A validated food frequency questionnaire (FFQ) was used to assess dietary intakes of participants. DAL was estimated using PRAL and DAL scores. Depression and anxiety were screened using Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI).

Results

In the fully adjusted model, women with the highest DAL or PRAL had higher odds of more severe depression compared to those in the lowest category (OR = 1.20; 95% CI = 1.03–1.42 and OR = 1.20; 95% CI = 1.03–1.39, respectively). No significant association was observed between DAL and PRAL and depression severity in men and in the population as a whole. Regarding the association between PRAL and anxiety severity, there was no significant association when separated by sex. However, in the fully adjusted model for the whole population, participants in the highest tertile of PRAL had 13% greater odds of more severe anxiety than the lowest tertile (OR: 1.13, 95% CI: 1.01–1.13). No significant association was observed between DAL and anxiety severity in women, men or in the whole population.

Conclusion

Women, but not men, with higher dietary acid load had significantly higher odds of having more severe depression. A significant positive association was also observed between dietary acid load and anxiety in the whole population.
Effectiveness of behavior change interventions for smoking cessation among expectant and new fathers: findings from a systematic review
Authors: Khanal Sudeepa , Miani Céline , Finne Emily , Zielke Julia , Boeckmann Melanie
Published: September 2023

Background

Smoking cessation during pregnancy and the postpartum period by both women and their partners offers multiple health benefits. However, compared to pregnant/postpartum women, their partners are less likely to actively seek smoking cessation services. There is an increased recognition about the importance of tailored approaches to smoking cessation for expectant and new fathers. While Behavior Change Interventions (BCIs) are a promising approach for smoking cessation interventions, evidence on effectiveness exclusively among expectant and new fathers are fragmented and does not allow for many firm conclusions to be drawn.

Methods

We conducted a systematic review on effectiveness of BCIs on smoking cessation outcomes of expectant and new fathers both through individual and/or couple-based interventions. Peer reviewed articles were identified from eight databases without any date or language restriction.Two independent reviewers screened studies for relevance, assessed methodological quality of relevant studies, and extracted data from studies using a predeveloped data extraction sheet.

Results

We retrieved 1222 studies, of which 39 were considered for full text screening after reviewing the titles and abstracts. An additional eight studies were identified from reviewing the reference list of review articles picked up by the databases search. A total of nine Randomised Control Trials were included in the study. Six studies targeted expectant/new fathers, two targeted couples and one primarily targeted women with an intervention component to men. While the follow-up measurements for men varied across studies, the majority reported biochemically verified quit rates at 6 months. Most of the interventions showed positive effects on cessation outcomes. BCI were heterogenous across studies. Findings are suggestive of gender targeted interventions being more likely to have positive cessation outcomes.

Conclusions

This systematic review found limited evidence supporting the effectiveness of BCI among expectant and new fathers, although the majority of studies show positive effects of these interventions on smoking cessation outcomes. There remains a need for more research targeted at expectant and new fathers. Further, there is a need to identify how smoking cessation service delivery can better address the needs of (all) gender(s) during pregnancy.
Mendelian randomization analysis to analyze the genetic causality between different levels of obesity and different allergic diseases
Authors: Li Yujian , Kan Xuan
Published: September 2023

Background

The causal relationship between obesity and different allergic diseases remains controversial.

Methods

The Two Sample MR package and Phenoscanner database were used to obtain and filter Genome-Wide Association Study (GWAS) data from the Open GWAS database. Mendelian randomization (MR) analysis was used to study the causal relationship between different levels of obesity and different allergic diseases. The data sets related to obesity and asthma were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened by the limma package. Cluster Profiler and GO plot packages were used for enrichment analysis to verify the results of MR analysis.

Results

Two-sample MR analysis showed a causal relationship between obesity and childhood allergy (age < 16), allergic asthma and atopic dermatitis (P < 0.05). In addition, there was also a causal relationship between allergic asthma and obesity (P < 0.05), while there was no genetic causal relationship between obesity and allergic rhinitis, eczema, lactose intolerance and so on (P > 0.05). Subgroup analysis revealed a causal relationship between both class 1 and class 2 obesity and childhood allergy (age < 16) (P < 0.05). Obesity class 1 was associated with allergic asthma, while obesity class 3 was associated with atopic dermatitis (P < 0.05). Bioinformatics analysis shows that there were common DEGs between obesity and allergic asthma.

Conclusion

Obesity is a risk factor for childhood allergy (age < 16), allergic asthma and atopic dermatitis, while allergic asthma is also a risk factor for obesity. Class 1 and class 2 obesity are both causally associated with childhood allergy (age < 16). In addition, there is a causal relationship between milder obesity and allergic asthma, while heavier obesity is causally related to atopic dermatitis.
Lower limb muscle strength and balance in older adults with a distal radius fracture: a systematic review
Authors: Forde Colin , Nicolson Philippa JA , Vye Charlotte , Pun Jessica CH , Sheehan Warren , Costa Matthew L , Lamb Sarah E , Keene David J
Published: September 2023

Background

Distal radius fractures are common fractures in older adults and associated with increased risk of future functional decline and hip fracture. Whether lower limb muscle strength and balance are impaired in this patient population is uncertain. To help inform rehabilitation requirements, this systematic review aimed to compare lower limb muscle strength and balance between older adults with a distal radius fracture with matched controls, and to synthesise lower limb muscle strength and balance outcomes in older adults with a distal radius fracture.

Methods

We searched Embase, MEDLINE, and CINAHL (1990 to 25 May 2022) for randomised and non-randomised controlled clinical trials and observational studies that measured lower limb muscle strength and/or balance using instrumented measurements or validated tests, in adults aged ≥ 50 years enrolled within one year after distal radius fracture. We appraised included observational studies using a modified Newcastle-Ottawa Scale and included randomised controlled trials using the Cochrane risk-of-bias tool. Due to the clinical and methodological heterogeneity in included studies, we synthesised results narratively in tables and text.

Results

Nineteen studies (10 case-control studies, five case series, and four randomised controlled trials) of variable methodological quality and including 1835 participants (96% women, mean age 55–73 years, median sample size 82) were included. Twelve included studies (63%) assessed strength using 10 different methods with knee extension strength most commonly assessed (6/12 (50%) studies). Five included case-control studies (50%) assessed lower limb strength. Cases demonstrated impaired strength during functional tests (two studies), but knee extension strength assessment findings were conflicting (three studies). Eighteen included studies (95%) assessed balance using 14 different methods. Single leg balance was most commonly assessed (6/18 (33%) studies). All case-control studies assessed balance with inconsistent findings.

Conclusion

Compared to controls, there is some evidence that older adults with a distal radius fracture have impaired lower limb muscle strength and balance. A cautious interpretation is required due to inconsistent findings across studies and/or outcome measures. Heterogeneity in control participants’ characteristics, study design, study quality, and assessment methods limited synthesis of results. Robust case-control and/or prospective observational studies are needed.

Registration

International prospective register of systematic reviews (date of registration: 02 July 2020, registration identifier: CRD42020196274).
Comparing the effectiveness of metformin with lifestyle modification for the primary prevention of type II diabetes: a systematic review and meta-analysis
Authors: Mousavi Sayedah Sarah , Namayandeh Seyedeh Mahdieh , Fallahzadeh Hossein , Rahmanian Masoud , Mollahosseini Mehdi
Published: September 2023

Background

Concerning ascending trend in the prevalence of chronic type II diabetes, prevention and the development of an effective approach after the recognition of at-risk individuals is crucial. This study aims to investigate comparing the influence of lifestyle modification and metformin interventions in the prevention of type II diabetes developments.

Method

The search was conducted using PubMed, Google Scholar, Scopus and Web of Science databases. The inclusion criteria include randomized controlled trials (RCT) which studied both lifestyle modification and metformin interventions in the population above 18 years old without a history of any type of diabetes. After excluding studies with intervention time of fewer than 6 months, a systematic review and meta-analysis were performed to evaluate relative risk (RR) with a confidence interval (CI) of 95% of type II diabetes development.

Results

Data from 5 studies were included in the meta-analysis. The population also consists of individuals with a mean age of 50 years old with BMI and FBS of 35.5 and 104.7 mg/dl respectively. Participants range of prevention years was between 2–3 years with a mean of 2.8 years. Lifestyle modification decreases the probability of the incidence of type II diabetes by 25.3% (RR: 0.747, 95% CI, 0.6—0.92) compared to the metformin intervention (p-value = 0.007). Our results indicate that long-term lifestyle modifications can prevent diabetes type II and decrease diabetes mellitus incidence down to one-quarter in comparison to metformin.

Conclusion

Lifestyle modification can be more efficacious than metformin in diminishing the incidence of type II diabetes. Therefore, lifestyle modification can be a therapeutic strategy for controlling type II diabetes incidence, especially in high-risk individuals.
Unexpected exacerbation of cryptococcal meningitis after unilateral adrenalectomy in a PMAH patient: a case report and literature review
Authors: Tan Lu , Zhao Lianling , Tang Guangmin , Ren Yan , Tian Haoming , Chen Tao
Published: September 2023

Background

Primary bilateral macronodular adrenal hyperplasia (PMAH) combined with infection by an opportunistic pathogen is complicated. Clinical evidence on managing PMAH patients with infections by opportunistic pathogens is insufficient.

Case presentation

A 66-year-old male was admitted with bilateral adrenal masses and was diagnosed with PMAH. Fever and disturbance of consciousness appeared after laparoscopic left adrenalectomy. Cryptococcal meningitis was confirmed by cerebrospinal fluid (CSF) culture. The exacerbation of his medical condition was suspected to result from immune reconstitution inflammatory syndrome (IRIS), and he had been treated with antifungal therapy and glucocorticoid replacement, but he responded poorly and eventually died of multiorgan failure. We summarized the clinical observations of 12 Cushing's syndrome (CS) patients infected by Cryptococcus. Seven out of nine patients who were treated for cryptococcus infection before receiving CS survived, while three patients treated for cryptococcus infection after CS treatment developed signs of IRIS and eventually died.

Conclusion

Cushing's syndrome, complicated with cryptococcal infection, has a high mortality rate, mainly when IRIS emerges. Carefully identifying the presence of the suspected infection, and controlling cryptococcal infection before removing the culprit adrenals could be the rational choice.
PR status is a more decisive factor in efficacy of adding pertuzumab into neoadjuvant therapy for HER2-positive and lymph node-positive breast cancer than ER status: a real-world retrospective study in China
Authors: Liu Xiaoyu , Liu Zhaoyun , Li Chao , Song Xiang , Wang Xinzhao , Li Sumei , Yu Zhiyong
Published: September 2023

Background

Although neoadjuvant trastuzumab and pertuzumab (HP)-based regimens are recommended for human epidermal receptor-positive (HER2 +)/lymph node-positive (N +) breast cancer (BC) patients according to NCCN guidelines, it is undeniable that many patients achieved pathological complete response (pCR) after trastuzumab (H)-based regimens without adding pertuzumab to treatment. Patients who specifically benefit from pertuzumab must be identified. The aim of this retrospective study was to evaluate progesterone receptor (PR) status as a predictor of response to the addition of pertuzumab in HER2 + /N + breast cancer.

Methods

One hundred forty-two patients who were diagnosed as HER2 + /N + BC without distant metastasis and followed by neoadjuvant HP-based or H-based therapy were retrospectively included. The endpoints were pCR and disease-free survival (DFS) times.

Results

In total, the pCR occurred in 25 of 87 patients (28.74%) in group H compared with 32 of 55 (58.18%) in group HP. The results revealed that hormone receptor (HR) status was significantly different on pCR in group HP. The odds of pCR for patients who have HR-positive tumors were 0.160 times (P = 0.011) that for patients with HR-negative tumors by multivariable analysis. Moreover, a similar probability of PR-positive (PR +) patients, whatever estrogen receptor (ER) status was, achieving pCR in group HP was observed. The ROC curves showed different anti-HER2 regimens provide worst predictive value in the PR + cohort (N = AUC = 0.521, 95% CI: 0.348–0.694, P = 0.813) compared with the overall cohort (AUC = 0.644, 95% CI: 0.550–0.738, P = 0.004) and ER + cohort (AUC: 0.559, 95% CI: 0.405–0.713, P = 0.451). And PR status (AUC = 0.760, 95% CI: 0.626–0.894, P = 0.001) had a greater predictive value than ER status (AUC = 0.658, 95% CI: 0.508–0.807, P = 0.048) in group HP. DFS analyses were done on 141 patients. Although ER and PR status did not show significant difference in group HP (P = 0.789 and 0.088, respectively), HP-based therapy contributed to better DFS in the ER − and PR − cohorts (P = 0.035 and 0.015, respectively).

Conclusions

Compared with ER status, PR status might be a more valuable factor predicting the efficacy of adding pertuzumab into neoadjuvant therapy for HER2 + /N + BC. PR + patients benefit little from the addition of pertuzumab.
GDF15 affects venous thrombosis by promoting EndMT through smad2/p-smad2 pathway
Authors: Li Yeping , Zhu Huiqi , Xin Wanghao , Wang Jiaoyan , Yan Chao , Ying Kejing
Published: September 2023

Background

Endothelial-to-mesenchymal transition (EndMT) is a pathophysiological change in the vascular endothelium commonly seen in the cardiovascular system. Elevated serum Growth differiention factor 15 (GDF15) has been reported in VTE patients, but the relationship and mechanism between GDF15, EndMT and VTE are still unclear.

Methods

We performed a retrospective clinical study, and human serum GDF15 expression levels were detected. The mouse DVT model was established through subtotal ligation of the mouse inferior vena cava, and then we detected intimal changes and thrombi in the stenotic inferior vena cava by haematoxylin-eosin (HE) staining, Masson staining, and Sirius Red staining. The expression levels of GDF15 and SM22 were detected by immunohistochemistry and RT‒qPCR. Serum samples of mice were collected, and the expression level of GDF15 in serum was detected. Human umbilical vein endothelial cells (HUVECs) were stimulated with a cytokine mixture (TGF-β1 + TNF-α + IL-1β). The role and mechanism of GDF15 in EndMT and VTE were detected in HUVECs and in a DVT mice model.

Results

We found that serum GDF15 levels in both VTE patients and mouse DVT models were higher than those in the control group. EndMT was increased in the stenotic vascular tissue of mice. Further experiments showed that GDF15 could promote the EndMT of HUVECs and reduce their anticoagulation and antifibrinolytic ability through the smad2/p-smad2/snail pathway. Inhibition of mature GDF15 release can significantly reduce venous thrombotic fibre deposition in mice.

Conclusions

GDF15 positively promotes EndMT through activation of the Smad2/psmad2/snail pathway, and inhibition of GDF15 expression can alleviate the EndMT process, further improving the coagulation and fibrinolytic function of endothelial cells and thus reducing the local fibre deposition of venous thrombi.
Psychosocial status and risk perception among Iranian healthcare workers during the fifth wave of the COVID-19 pandemic
Authors: Khazaee-Pool Maryam , Moradi Masoud , Pashaei Tahereh , Ponnet Koen
Published: September 2023

Background

Healthcare workers (HCWs) are essential resources, and their health and wellbeing are key not only for offering constant and useful care facilities to clients, but also for maintaining the safety of the workforce and patients. The risk of severe mental health problems among HCWs may have increased during large outbreaks of COVID-19. To evaluate the psychosocial status and risk perception of HCWs who participated in treating COVID-19 patients in Northern Iran, we performed a web-based cross-sectional study.

Methods

The web-based cross-sectional design was applied between June 27 and September 2, 2021. Using convenience sampling, 637 HCWs were recruited from hospitals in Northern Iran (Mazandaran). The HCWs completed self-report questionnaires that included a sociodemographic information form, the 12-item General Health Questionnaire, Impact of the Event Scale-Revised, Risk Perception Questionnaire, and Anxiety Stress Scale‐21. The data were analyzed via descriptive and inferential statistics and univariate/multivariate logistic regression to assess the risk factors linked to each psychosocial consequence.

Results

The results reveal that the COVID-19 pandemic had an adverse psychosocial influence on HCWs, which was already apparent 1.5 years after the crisis began. Based on the results, 71.6%, 55.6%, and 32.3% of HCWs reported having anxiety, depression, and stress symptoms, respectively, since the outbreak of this disease. The logistic regression models displayed that marital status, having children, and working hours with patients were all risk factors of psychosocial impairment.

Conclusions

The outbreak of COVID-19 can be considered an important experience of a bio-disaster resulting in a significant rate of psychiatric problems in HCWs. There is a need for designing and promoting supportive programs to help HCWs cope and to improve their psychosocial state, and the present study has detected for whom psychosocial support may be effective and practical 1.5 years after the primary outbreak. Moreover, detecting and managing concerns and reducing infection-related embarrassment/stigma are essential for improving HCWs’ mental health.
Resilience of primary healthcare system across low- and middle-income countries during COVID-19 pandemic: a scoping review
Authors: Pradhan Nousheen Akber , Samnani Amir Ali Barket Ali , Abbas Kiran , Rizvi Narjis
Published: September 2023

Introduction

Globally, the coronavirus disease 2019 (COVID-19) pandemic tested the resilience of the health system and its shock-absorbing capacity to continue offering healthcare services. The available evidences does not provide comprehensive insight into primary health care (PHC) system functioning across low- and middle- income countries (LMICs) during the pandemic. Therefore, the objective of this scoping review was to generate evidence on the resilience of PHC systems in LMICs during the COVID-19 pandemic.

Methods

A scoping review was carried out utilizing an iterative search strategy using the National Library of Medicine (NLM) and the WHO COVID-19 electronic databases. Data from the identified studies in LMICs were charted in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist in the first step. The analysis framework was adapted and modified using COVID-19 and health systems resilience framework developed by Sagan et al., Blanchet et al., and the WHO position paper on ‘Building health systems resilience for universal health coverage and health security during the COVID-19 pandemic and beyond’. A total of 26 documents were included on the basis of predefined eligibility criteria for our analysis.

Results

Our review explored data from 44 LMICs that implemented strategies at the PHC level during the COVID-19 pandemic. Most of the LMICs developed national guidelines on sexual, reproductive, maternal, newborn, child, and adolescent health (SRMNCAH). Most of the countries also transformed and reoriented PHC service delivery by introducing digital healthcare services to continue essential services. Task shifting, task sharing, and redeployment of retired staff were some frequently adopted health workforce strategies adopted by most of the countries. Only a few of the countries demonstrated the availability of necessary monetary resources to respond to the pandemic.

Conclusions

The functionality of the PHC system during the COVID-19 pandemic was demonstrated by a variety of resilience strategies across the six building blocks of the health system. To strengthen PHC resilience, we recommend strengthening community-based PHC, cross-sectoral collaboration, establishing surveillance systems, capacity building in financial risk planning, and investing in strengthening the digital healthcare system.
The discovery, structure, and function of 5-HTR1E serotonin receptor
Authors: Sharma Vinay Kumar , Loh Y. Peng
Published: September 2023

Serotonin (5-hydroxytryptamine, 5-HT) is a unique neurotransmitter which can regulate various biological processes by activating thirteen different receptors. These serotonin receptors are divided into seven different classes based on their structure and functions. Since these receptors co-express in various tissue and cell types and share the same ligand (5-HT), it has been a challenge for the researchers to define specific pathway and separate physiological role for each of these serotonin receptors. Though the evidence of operational diversity of these receptors is continuously emerging, much work remains to be done. 5-HTR1E is a member of 5-HT1 receptor family which belongs to G-protein coupled receptors (GPCRs). Even after three decades since its discovery, 5-HTR1E remains the least explored serotonin receptor. Very high similarity with another family member (5-HTR1F) and its non-existence in mice or rats makes 5-HTR1E a difficult target to study. Despite these challenges, recent findings on the role of 5-HTR1E in neuroprotection and diseases such as cancer, have excited many researchers to explore this receptor in detail. Here, we provide the first review of 5-HTR1E, since its discovery in 1989 to 2023. We highlight the structural and functional characteristics of this important serotonin receptor in detail and propose future directions in developing 5-HTR1E as a drug target.
Arginase-1 promotes lens epithelial-to-mesenchymal transition in different models of anterior subcapsular cataract
Authors: Li Qingyu , Wang Yuchuan , Shi Luoluo , Wang Qing , Yang Guang , Deng Lin , Tian Ye , Hua Xia , Yuan Xiaoyong
Published: September 2023

Background

Arginase-1 (ARG1) promotes collagen synthesis and cell proliferation. ARG1 is highly expressed in various tumour cells. The mechanisms of ARG1 in epithelial-to-mesenchymal transition (EMT)-associated cataracts were studied herein.

Methods

C57BL/6 mice, a human lens epithelial cell line (HLEC-SRA01/04), and human lens capsule samples were used in this study. The right lens anterior capsule of the mouse eye was punctured through the central cornea with a 26-gauge hypodermic needle. Human lens epithelial cells (HLECs) were transfected with ARG1-targeted (siARG1) or negative control siRNA (siNC). For gene overexpression, HLECs were transfected with a plasmid bearing the ARG1 coding sequence or an empty vector. Medium containing 0.2% serum with or without transforming growth factor beta-2 (TGF-β2) was added for 6 or 24 h to detect mRNA or protein, respectively. The expression of related genes was measured by quantitative real-time polymerase chain reaction (RT–qPCR), western blotting, and immunohistochemical staining. Transwell assays and wound healing assays were used to determine cell migration. Cell proliferation, superoxide levels, nitric oxide (NO) levels, and arginase activity were estimated using Cell Counting Kit-8 assays, a superoxide assay kit, an NO assay kit, and an arginase activity kit.

Results

ARG1, alpha-smooth muscle actin (α-SMA), fibronectin, and Ki67 expression increased after lens capsular injury, while zonula occludens-1 (ZO-1) expression decreased.

Fibronectin and collagen type I alpha1 chain (collagen 1A1) expression increased, and cell migration increased significantly in ARG1-overexpressing HLECs compared with those transfected with an empty vector after TGF-β2 treatment. These effects were reversed by ARG1 knockdown.

The arginase-related pathway plays an important role in EMT. mRNAs of enzymes of the arginase-related pathway were highly expressed after ARG1 overexpression. ARG1 knockdown suppressed these expression changes.

Numidargistat (CB-1158) dihydrochloride (CB-1158), an ARG1 inhibitor, suppressed TGF-β2-induced anterior subcapsular cataract (ASC) by reducing the proliferation of lens epithelial cells (LECs) and decreasing fibronectin, α-SMA, collagen 1A1, and vimentin expression.

Compared with that in nonanterior subcapsular cataract (non-ASC) patients, the expression of ARG1, collagen 1A1, vimentin, fibronectin, and Ki67 was markedly increased in ASC patients.

Conclusions

ARG1 can regulate EMT in EMT-associated cataracts. Based on the pathogenesis of ASC, these findings are expected to provide new therapeutic strategies for patients.

Graphical abstract
A glycosylated Phr1 protein is induced by calcium stress and its expression is positively controlled by the calcium/calcineurin signaling transcription factor Crz1 in Candida albicans
Authors: Jiang Linghuo , Xu Huihui , Gu Yiying , Wei Liudan
Published: September 2023

As one of the most important human fungal pathogens, Candida albicans senses and adapts to host niches with different pH values through the pH-responsive Rim101 pathway. Its transcription factor Rim101 activates the expression of alkaline pH-induced genes including PHR1 that encodes a glycosylphosphatidylinsitol-anchored β(1,3)-glucanosyltransferase critical for hyphal wall formation. The calcium/calcineurin signaling pathway is mediated by the transcription factor Crz1 in yeasts and other lower eukaryotes. Here we report that deletion of PHR1 leads to calcium sensitivity of C. albicans cells. In addition, expression of Phr1 is induced by calcium stress and under the control of Crz1 in C. albicans. EMSA assay demonstrates that Crz1 binds to one CDRE element in the PHR1 promoter. Alkaline treatment induces two species of glycosylated Phr1 proteins with different degrees of glycosylation, which is independent of Crz1. In contrast, only one species of Phr1 protein with a low degree of glycosylation is induced by calcium stress in a Crz1-dependent fashion. Therefore, we have provided an evidence that regulation of cell wall remodeling is integrated through differential degrees of Phr1 glycosylation by both the pH-regulated Rim101 pathway and the calcium/calcineurin signaling pathway in C. albicans.
LFA-1 knockout inhibited the tumor growth and is correlated with treg cells
Authors: Niu Ting , Li Zhengyang , Huang Yiting , Ye Yuxiang , Liu Yilong , Ye Zhijin , Jiang Lingbi , He Xiaodong , Wang Lijing , Li Jiangchao
Published: September 2023

Cancer immunotherapy has been proven to be clinically effective in multiple types of cancers. Lymphocyte function-associated antigen 1 (LFA-1), a member of the integrin family of adhesion molecules, is expressed mainly on αβ T cells. LFA-1 is associated with tumor immune responses, but its exact mechanism remains unknown. Here, two kinds of mice tumor model of LFA-1 knockout (LFA-1−/−) mice bearing subcutaneous tumor and ApcMin/+;LFA-1−/− mice were used to confirm that LFA-1 knockout resulted in inhibition of tumor growth. Furthermore, it also demonstrated that the numbers of regulatory T cells (Treg cells) in the spleen, blood, mesenteric lymph nodes were decreased in LFA-1−/− mice, and the numbers of Treg cells in mesenteric lymph nodes were also decreased in ApcMin/+;LFA-1−/− mice compared with ApcMin/+ mice. LFA-1 inhibitor (BIRT377) was administered to subcutaneous tumor-bearing LFA-1+/+ mice, and the results showed that the tumor growth was inhibited and the number of Treg cells was reduced. The analysis of TIMER tumor database indicated that LFA-1 expression is positively associated with Treg cells and TNM stage. Conclusively, this suggests that LFA-1 knockout would inhibit tumor growth and is correlated with Treg cells. LFA-1 may be one potential target for cancer immunotherapy.
GPR65 inhibits human trophoblast cell adhesion through upregulation of MYLK and downregulation of fibronectin via cAMP-ERK signaling in a low pH environment
Authors: Mao Jia , Feng Ying , Zheng Yayun , Gao Yaqiu , Zhang Linyu , Sun Xinrui , Wu Yilun , Zhu Xiaofeng , Ma Fang
Published: September 2023

Background

Extravillous trophoblasts (EVTs) are essential cells during the formation of the placenta, with the major function of invading the maternal decidua, anchoring the developing placenta to the uterus, remodeling uterine arteries, and regulating immune responses to prevent rejection. During early pregnancy, the decidua undergoes a hypoxic and acidic microenvironment, which has been shown to participate in tumor cell migration, invasion, growth, and angiogenesis. Nevertheless, the mechanisms by which EVTs sense and respond to the acidic microenvironment, thereby executing their functions, remain poorly understood.

Methods

The effects of G protein-coupled receptor 65 (GPR65) on cell adhesion and other cellular functions were tested using JAR spheroids, mouse blastocysts, and HTR-8/SVneo cells. Specifically, we employed HTR-8/SVneo cells for gene overexpression and silencing to investigate the underlying mechanism of GPR65's impact on trophoblast cell function under acidic conditions. Additionally, villus tissue samples obtained from early pregnancy loss patients were utilized to explore the potential association between GPR65 and its related signaling pathway molecules with the disease.

Results

This study identified GPR65 expression widely in trophoblasts, with the highest level in EVTs. Importantly, optimal GPR65 levels are required for maintaining normal adhesion, migration, and invasion, whereas overexpression of GPR65 inhibits these functions by activating the cAMP-ERK signaling pathway, upregulating myosin light chain kinase (MYLK) and MYLK3 expression, and subsequently downregulating fibronectin. Consistently, elevated expression of GPR65, MYLK, and MYLK3 is observed in patients suffering from early pregnancy loss.

Conclusions

This work offers insights into the suppressive effects of GPR65 on EVT function under acidic conditions and highlights a putative target for therapeutic intervention in early pregnancy complications.
Regulation of phosphoglycerate kinase 1 and its critical role in cancer
Authors: Zhang Kexin , Sun Lixue , Kang Yuanyuan
Published: September 2023

Cells that undergo normal differentiation mainly rely on mitochondrial oxidative phosphorylation to provide energy, but most tumour cells rely on aerobic glycolysis. This phenomenon is called the "Warburg effect". Phosphoglycerate kinase 1 (PGK1) is a key enzyme in aerobic glycolysis. PGK1 is involved in glucose metabolism as well as a variety of biological activities, including angiogenesis, EMT, mediated autophagy initiation, mitochondrial metabolism, DNA replication and repair, and other processes related to tumorigenesis and development. Recently, an increasing number of studies have proven that PGK1 plays an important role in cancer. In this manuscript, we discussed the effects of the structure, function, molecular mechanisms underlying PGK1 regulation on the initiation and progression of cancer. Additionally, PGK1 is associated with chemotherapy resistance and prognosis in tumour patients. This review presents an overview of the different roles played by PGK1 during tumorigenesis, which will help in the design of experimental studies involving PGK1 and enhance the potential for the use of PGK1 as a therapeutic target in cancer.