bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report: Tongdu Xingshen acupuncture for a patient with persistent vegetative state after herpes simplex virus encephalitis
Authors: Jin Bingxu , Tang Yuyuan , Wu Yunyun , Liu Zhenhuan
Published: October 2022

Introduction

A persistent vegetative state (PVS) can be caused by traumatic or non-traumatic brain injury. PVS is a complex clinical condition with numerous complications. Nursing care, medical treatment, and comprehensive rehabilitation are necessary to improve the outcomes of PVS. However, the prognosis remains unsatisfactory. Acupuncture therapy has been used as a rehabilitation strategy to treat patients with PVS in China, showing better results in the recovery of consciousness, intellectual capability, and motor function.

Case description

We present the case of a 4-month-long PVS after herpes simplex virus encephalitis (HSVE) in a 3.5-year-old boy who underwent Tongdu Xingshen acupuncture integrated with Western medicine and rehabilitation. The patient regained consciousness post-treatment. His intelligence and motor function gradually recovered after seven treatment sessions.

Conclusion

Tongdu Xingshen acupuncture is a potential complementary therapy to optimize clinical outcomes in PVS.
Association between dietary intake of fatty acids and colorectal cancer, a case-control study
Authors: Shekari Soheila , Fathi Soroor , Roumi Zahra , Akbari Mohammad Esmail , Tajadod Shirin , Afsharfar Maryam , Hasanpour Ardekanizadeh Naeemeh , Bourbour Fatemeh , Keshavarz Seyed Ali , Sotoudeh Mahtab , Gholamalizadeh Maryam , Nemat Gorgani Shiva , Shafaei Kachaei Hanieh , Alizadeh Atiyeh , Doaei Saeid
Published: October 2022

Background

The association of dietary fat and colorectal cancer (CRC) was frequently reported. However, few studies assessed the effects of different types of dietary fats on CRC. This study aimed to investigate the association between intakes of different types of dietary fatty acids with colorectal cancer risk.

Methods

This case-control study was conducted on 480 participants including 160 CRC cases and 320 healthy controls in Firoozgar Hospital, Tehran, Iran. The intake of dietary fatty acids of the participants was assessed using a semi quantitative food frequency questionnaire (FFQ).

Results

The mean intake of cholesterol (273.07 ± 53.63 vs. 254.17 ± 61.12, P = 0.001), polyunsaturated fatty acids (PUFA) (16.54 ± 4.20 vs. 15.41 ± 4.44, P = 0.012), and calorie (2,568.76 ± 404.48 vs. 2,493.38 ± 176.03, P = 0.006) was higher and the mean intake of oleic acid (5.59 ± 3.17 vs. 8.21 ± 5.46) and linoleic acid (6.03 ± 3.44 vs. 7.02 ± 4.08, P = 0.01) was lower in the case group compared to the control group. An inverse association was found between colorectal cancer (CRC) and dietary intake of oleic acid (OR: 0.85, CI 95% 0.80–0.90, P = 0.001), linoleic acid (OR: 0.85, CI 95% 0.78–0.93, P = 0.001), and α-linolenic acid (OR: 0.75, CI 95% 0.57–0.98, P = 0.04). The association remained significant after adjusting for age and sex, sleep, smoking, and alcohol consumption, and BMI.

Conclusions

The results of this study support a protective effect of oleic acid, linoleic acid, and α-linolenic acid against CRC. Further longitudinal studies are warranted to confirm these results.
Prevalence, trend, and predictor analyses of vitamin D deficiency in the US population, 2001–2018
Authors: Cui Aiyong , Xiao Peilun , Ma Yuzhuo , Fan Zhiqiang , Zhou Fengjin , Zheng Jiang , Zhang Liang
Published: October 2022

Background

The National Health and Nutrition Examination Surveys (NHANES) collect and release data to the public every 2 years. The latest NHANES study on the vitamin D status of Americans was based on data from 2001 to 2014, and the latest data (2015–2016 and 2017–2018) have not been studied yet. Thus, we extracted all the available data from NHANES (2001–2018), aiming to analyze the prevalence and trends of vitamin D deficiency (VDD) in the US population to bridge the research gap.

Methods

According to previous studies and nutritional guidelines for vitamin D, severe VDD was defined as serum 25(OH)D levels of <25 nmol/L, moderate deficiency as 25–50 nmol/L, insufficiency as 50–75 nmol/L, and sufficiency as >75 nmol/L. We comprehensively estimated the prevalence of serum 25(OH)D levels of <25, 25–50, 50–75, and >75 nmol/L in Americans and described trends in vitamin D status from 2001 to 2018. Weighted multivariate linear regression models were used to explore the predictors of VDD. All analyses and the data were adjusted for the complex sampling design of NHANES using Mobile Examination Center (MEC) weights.

Results

Based on the most recent data of 71,685 participants, our study showed that the weighted prevalence of severe and moderate VDD was 2.6% and 22.0%, and the prevalence of vitamin D insufficiency (VDI) and sufficiency was 40.9% and 34.5%. The prevalence of severe and moderate VDD was higher in women, non-Hispanic black Americans, people aged 20–29 years, and during the season of winter. From 2001 to 2018, we found a slight linear decrease in the prevalence of moderate VDD (coefficient = −0.847; P = 0.009) and VDI (coefficient = −0.810; P = 0.014). We also found a slight linear increase in vitamin D sufficient (coefficient = 1.693; P = 0.004). However, no trend change was observed in severe VDD (coefficient = −0.037; P = 0.698). Age, sex, ethnicity, season, sun-protective behaviors, lower BMI, lower socioeconomic status (SES), drinking, and lower milk consumption were predictors of severe VDD.

Conclusion

Vitamin D deficiency is still prevalent in the United States, especially in non-Hispanic black Americans, women, individuals aged 20–29, and during winter. Therefore, individuals, healthcare providers, and policymakers should take public health measures to develop and implement prevention strategies to deal with VDD.
A rare case of prostate neuroendocrine tumor: A case report
Authors: Teh Shunxing , Inn Fam Xeng , Rizuana Iqbal Hussain , WM Wan Muhaizan
Published: October 2022

Small cell prostate neuroendocrine carcinoma (SCPC) is a rare and highly aggressive malignant tumor. We present a case of a 52-year-old Iranian man, presenting with complaints of occasional gross hematuria and perineal pain for 6 months. PSA was 0.8 ng/ml. A digital rectal examination found a huge and hard prostate mass. He underwent a transrectal ultrasound-guided (TRUS) biopsy of the prostate. Histopathology showed high-grade small cell neuroendocrine carcinoma. Immunohistochemical markers were positive for synaptophysin with a Ki67 index of almost 100%. However, CD56 and chromogranin A markers were negative. Magnetic resonance imaging (MRI) of the prostate showed a prostate mass with invasion to the rectum, while contrast-enhanced computed tomography of the thorax, abdomen, and pelvis (CT TAP) ruled out metastasis. A multidisciplinary team discussion was carried out, and a decision was made for concurrent chemotherapy and radiation (cisplatin and etoposide for 4 cycles and 70 Gy, 35 fractions). There is a lack of consensus on the management of SCPC. The main modality of management in advanced (stage IV) disease is chemotherapy. It is a highly aggressive tumor with a poor prognosis and is not responsive to hormonal therapy.
ASAP Score versus GALAD Score for detection of hepatitis C-related hepatocellular carcinoma: A multicenter case-control analysis
Authors: Liu Si-Yu , Li Chao , Sun Li-Yang , Guan Ming-Cheng , Gu Li-Hui , Yin Dong-Xu , Yao Lan-Qing , Liang Lei , Wang Ming-Da , Xing Hao , Zhu Hong , Pawlik Timothy M. , Lau Wan Yee , Shen Feng , Tong Xiang-Min , Yang Tian
Published: October 2022

Background

The GALAD and ASAP scores are two well-recognized algorithms to estimate the risk of hepatocellular carcinoma (HCC) based on gender, age, alpha-fetoprotein (AFP), protein induced by vitamin K absence or Antagonist-II (PIVKA-II) and AFP-L3 (included in the GALAD score but not in the ASAP score). The current study sought to compare the diagnostic performance of each score to detect HCC among patients infected with hepatitis C virus (HCV).

Methods

A multicenter case-control study was undertaken in which blood samples were collected from HCVinfected patients with and without HCC. Using the area under the receiver operating characteristic curve (AUROC), ASAP and GALAD scores were compared relative to diagnostic performance to detect any stage HCV-HCC and early-stage HCV-HCC.

Results

The analytic cohort included 168 HCV-HCC patients and a control group of 193 HCV-infected patients. The ASAP score had a higher AUROC to detect any stage HCV-HCC versus the GALAD score, both in the overall group (0.917 vs. 0.894, P=0.057) and in the cirrhosis subgroup (0.909 vs. 0.889, P=0.132). Similar results were noted relative to the detection of early-stage HCV-HCC, whether defined by BCLC staging (stage 0-A: 0.898 vs. 0.860, P=0.026) or 8th TNM staging (stage I: 0.899 vs. 0.870, P=0.070). In subgroup analysis to detect AFP-negative HCV-HCC, the ASAP score also demonstrated a higher AUROC than the GALAD score to detect any stage HCV-HCC in the AFP-negative subgroup (0.815 vs. 0.764, P=0.063).

Conclusions

The ASAP score had better diagnostic performance for early detection of HCV-HCC compared with the GALAD score. The ASAP score may be preferrable to the GALAD score for HCC screening and surveillance among HCV-infected patients.
Targeting phase separation on enhancers induced by transcription factor complex formations as a new strategy for treating drug-resistant cancers
Authors: Takayama Ken-ichi , Inoue Satoshi
Published: October 2022

The limited options for treating patients with drug-resistant cancers have emphasized the need to identify alternative treatment targets. Tumor cells have large super-enhancers (SEs) in the vicinity of important oncogenes for activation. The physical process of liquid-liquid phase separation (LLPS) contributes to the assembly of several membrane-less organelles in mammalian cells. Intrinsically disordered regions (IDRs) of proteins induce LLPS formation by developing condensates. It was discovered that key transcription factors (TFs) undergo LLPS in SEs. In addition, TFs play critical roles in the epigenetic and genetic regulation of cancer progression. Recently, we revealed the essential role of disease-specific TF collaboration changes in advanced prostate cancer (PC). OCT4 confers epigenetic changes by promoting complex formation with TFs, such as Forkhead box protein A1 (FOXA1), androgen receptor (AR) and Nuclear respiratory factor 1 (NRF1), inducing PC progression. It was demonstrated that TF collaboration through LLPS underlying transcriptional activation contributes to cancer aggressiveness and drug resistance. Moreover, the disruption of TF-mediated LLPS inhibited treatment-resistant PC tumor growth. Therefore, we propose that repression of TF collaborations involved in the LLPS of SEs could be a promising strategy for advanced cancer therapy. In this article, we summarize recent evidence highlighting the formation of LLPS on enhancers as a potent therapeutic target in advanced cancers.
Integrated computer analysis and a self-built Chinese cohort study identified GSTM2 as one survival-relevant gene in human colon cancer potentially regulating immune microenvironment
Authors: Zhang Wei , Shi Yutong , Niu Shumeng , Li Lintai , Lin Liewen , Gao Xucan , Cai Wanxia , Chen Yumei , Zhong Yafang , Tang Donge , Tang Min , Dai Yong
Published: October 2022

According to a recent report by GLOBOCAN, colorectal cancer is the third most common and second most deadly cancer in 2020. In our previous proteomic study, we found that the expression of GSTM2 in colon tissues was significantly lower than that in para-cancer tissues, and its lower expression was associated with reduced overall survival rate of patients, suggesting that this gene might play a role in the occurrence of colon cancer. As a member of the detoxifying enzyme family, GSTM2 is likely to play an important role in the initiation of tumors. Whereas, the functions of GSTM2 in colon cancer are barely known. In this study, using the RNA-Seq datasets of colon cancer patients from public database (ntumor = 457, nnormal = 41), we confirmed the reduced expression of GSTM2 and its prognostic value in colon cancer. Furthermore, we used our own Chinese cohort (ntumor = 100, nnormal = 72) verified the lower GSTM2 expression in colon cancer, and also its effects on patient prognosis. Subsequently, we uncovered two potential reasons for the lower expression of GSTM2 in colon cancer tissues, including the deep deletion of GSTM2 on genome, and the up-regulation of RAD21 or SP1. Moreover, we disclosed that GSTM2 might be involved in several immune-related pathways in colon cancer, such as chemokine signaling and leukocyte transendothelial migration. Finally, we revealed that the GSTM2 expression was closely related to the immune-related scores of colon cancer and the infiltration ratios of various immune cells, suggesting that GSTM2 might regulate the development of colon cancer by modulating immune microenvironment. In conclusion, we uncovered the prognostic value of GSTM2 based on the public data and our own data, revealed its potential regulatory role in tumor immune microenvironment, and disclosed the probable reasons for its lower expression in colon cancer. The findings of our study provide a potential prognostic biomarker and drug target for clinical diagnosis and treatment of colon cancer.
Causal effects of systemic lupus erythematosus on endometrial cancer: A univariable and multivariable Mendelian randomization study
Authors: Wan An , Zhao Wei-Dong , Tao Jin-Hui
Published: October 2022

Objective

Systemic lupus erythematosus (SLE) has been observationally associated with endometrial cancer, but the causality remains unclear. Here, we investigated for the first time the causal links between SLE and endometrial cancer risk.

Methods

Univariable and multivariable Mendelian randomization (MR) analyses were conducted to disentangle the causality of SLE with endometrial cancer. Apart from the inverse-variance weighted (IVW) method as the primary MR estimate, three complementary MR techniques including weighted median, weighted mode, and MR-Egger regression in univariable MR were conducted to clarify the robustness of the causal estimate and mediation effects of the body mass index (BMI) and were investigated within multivariable MR-IVW and MR-Egger analyses.

Results

All univariable MR analyses consistently suggested that SLE has a protective effect on the risk of overall endometrial cancer (IVW: OR = 0.956, 95% CI = 0.932-0.981, P = 0.001) and endometrioid endometrial cancer (IVW: OR = 0.965, 95% CI = 0.933-0.999, P = 0.043). More compelling, after adjustment for BMI within the multivariable MR setting, the association between SLE and decreased risk of overall endometrial cancer was significantly stronger (IVW: OR = 0.952, 95% CI = 0.931-0.973, P = 9.58E-06).

Conclusions

Our findings provide evidence of a significant causal relationship between SLE and decreased endometrial cancer risk. Further understanding of the underlying mechanisms linking SLE with endometrial cancer is therefore needed.
Myocardial edema during chemotherapy for gynecologic malignancies: A cardiac magnetic resonance T2 mapping study
Authors: Yang Meng-Xi , Li Qing-Li , Wang Dan-Qing , Ye Lu , Li Ke-Min , Lin Xiao-Juan , Li Xue-Sheng , Fu Chuan , Ma Xin-Mao , Liu Xi , Yin Ru-Tie , Yang Zhi-Gang , Guo Ying-Kun
Published: October 2022

Objective

Myocardial edema is an early manifestation of chemotherapy-related myocardial injury. In this study, we used cardiac magnetic resonance (CMR) T2 mapping to assess myocardial edema and its changes during chemotherapy for gynecologic malignancies.

Methods

We enrolled 73 patients receiving chemotherapy for gynecologic malignancies, whose the latest cycle was within one month before the beginning of this study, and 41 healthy volunteers. All participants underwent CMR imaging. Of the 73 patients, 35 completed CMR follow-up after a median interval of 6 (3.3 to 9.6) months. The CMR sequences included cardiac cine, T2 mapping, and late gadolinium enhancement.

Results

Myocardial T2 was elevated in patients who were treated with chemotherapy compared with healthy volunteers [41ms (40ms to 43ms) vs. 41ms (39ms to 41ms), P = 0.030]. During follow-up, myocardial T2 rose further [40ms (39ms to 42ms) vs. 42.70 ± 2.92ms, P < 0.001]. Multivariate analysis showed that the number of chemotherapy cycles was associated with myocardial T2 elevation (β = 0.204, P = 0.029). After adjustment for other confounders, myocardial T2 elevation was independently associated with a decrease in left ventricular mass (β = −0.186; P = 0.024).

Conclusion

In patients with gynecologic malignancies, myocardial edema developed with chemotherapy cycles increase, and was associated with left ventricular mass decrease. T2 mapping allows the assessment of myocardial edema and monitoring of its change during chemotherapy.
Fibroblast activation protein-based theranostics in pancreatic cancer
Authors: Cheng Chien-shan , Yang Pei-wen , Sun Yun , Song Shao-li , Chen Zhen
Published: October 2022

Fibroblast activation protein-α (FAP) is a type II transmembrane serine protease that has specific endopeptidase activity. Given its well-established selective expression in the activated stromal fibroblasts of epithelial cancers, although not in quiescent fibroblasts, FAP has received substantial research attention as a diagnostic marker and therapeutic target. Pancreatic cancer is characterized by an abundant fibrotic or desmoplastic stroma, leading to rapid progression, therapeutic resistance, and poor clinical outcomes. Numerous studies have revealed that the abundant expression of FAP in cancer cells, circulating tumor cells, stromal cells, and cancer-associated fibroblasts (CAFs) of pancreatic adenocarcinoma is implicated in diverse cancer-related signaling pathways, contributing to cancer progression, invasion, migration, metastasis, immunosuppression, and resistance to treatment. In this article, we aim to systematically review the recent advances in research on FAP in pancreatic adenocarcinoma, including its utility as a diagnostic marker, therapeutic potential, and correlation with prognosis. We also describe the functional role of FAP-overexpressing stromal cells, particulary CAFs, in tumor immuno- and metabolic microenvironments, and summarize the mechanisms underlying the contribution of FAP-overexpressing CAFs in pancreatic cancer progression and treatment resistance. Furthermore, we discuss whether targeting FAP-overexpressing CAFs could represent a potential therapeutic strategy and describe the development of FAP-targeted probes for diagnostic imaging. Finally, we assess the emerging basic and clinical studies regarding the bench-to-bedside translation of FAP in pancreatic cancer.
Nimotuzumab combined with chemoradiotherapy for the treatment of cervical cancer: A meta-analysis of randomized controlled trials
Authors: Yuan Yan , Chen Jiuzhou , Fang Miao , Guo Yaru , Sun Xueqing , Yu Dehong , Guo Yilong , Xin Yong
Published: October 2022

Objectives

To assess the clinical efficacy and toxicity of nimotuzumab in combination with chemoradiotherapy or chemoradiotherapy alone in the treatment of cervical cancer.

Methods

The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biomedical Medicine, Wanfang, and VIP databases were systematically searched for relevant literature. Ultimately, six randomised controlled trials (n=393) were included in our meta-analysis.

Results

A total of 393 patients were included, of which 197 were in the nimotuzumab combined with chemoradiotherapy group and 196 were in the chemoradiotherapy group. The results of our meta-analysis showed that the complete remission rate (risk ratio [RR] = 1.34, 95% confidence interval [CI]: 1.08-1.65, P = 0.007), objective response rate (RR = 1.30, 95% CI: 1.16-1.44, P < 0.05), and three-year survival rate (RR = 1.27, 95% CI: 1.06-1.51, P = 0.008) in the nimotuzumab combined with chemoradiotherapy group were significantly improved compared with the chemoradiotherapy group. This difference was not statistically significant when comparing the incidence of adverse reactions (such as leukocytopenia, gastrointestinal reaction, radiocystitis, and radioproctitis) between the two groups.

Conclusions

Nimotuzumab in combination with chemoradiotherapy has some advantages over chemoradiotherapy alone in the treatment of cervical cancer and does not increase toxicity. Therefore, nimotuzumab has the potential to be an effective treatment for cervical cancer; however, further evidence from large-scale randomised controlled trials is needed.
Confocal laser imaging in neurosurgery: A comprehensive review of sodium fluorescein-based CONVIVO preclinical and clinical applications
Authors: Restelli Francesco , Mathis Andrea Maria , Höhne Julius , Mazzapicchi Elio , Acerbi Francesco , Pollo Bianca , Quint Karl
Published: October 2022

Given the established direct correlation that exists among extent of resection and postoperative survival in brain tumors, obtaining complete resections is of primary importance. Apart from the various technological advancements that have been introduced in current clinical practice, histopathological study still remains the gold-standard for definitive diagnosis. Frozen section analysis still represents the most rapid and used intraoperative histopathological method that allows for an intraoperative differential diagnosis. Nevertheless, such technique owes some intrinsic limitations that limit its overall potential in obtaining real-time diagnosis during surgery. In this context, confocal laser technology has been suggested as a promising method to have near real-time intraoperative histological images in neurosurgery, thanks to the results of various studies performed in other non-neurosurgical fields. Still far to be routinely implemented in current neurosurgical practice, pertinent literature is growing quickly, and various reports have recently demonstrated the utility of this technology in both preclinical and clinical settings in identifying brain tumors, microvasculature, and tumor margins, when coupled to the intravenous administration of sodium fluorescein. Specifically in neurosurgery, among different available devices, the ZEISS CONVIVO system probably boasts the most recent and largest number of experimental studies assessing its usefulness, which has been confirmed for identifying brain tumors, offering a diagnosis and distinguishing between healthy and pathologic tissue, and studying brain vessels. The main objective of this systematic review is to present a state-of-the-art summary on sodium fluorescein-based preclinical and clinical applications of the ZEISS CONVIVO in neurosurgery.
Parental responses and catastrophizing in online cognitive behavioral therapy for pediatric functional abdominal pain: A mediation analysis of a randomized controlled trial
Authors: Lalouni Maria , Bujacz Aleksandra , Bonnert Marianne , Jensen Karin B. , Rosengren Anna , Hedman-Lagerlöf Erik , Serlachius Eva , Olén Ola , Ljótsson Brjánn
Published: October 2022

Objective

To test if decreased parental protective behaviors, monitoring behaviors, and parental catastrophizing mediate relief of gastrointestinal symptoms in children 8–12 years with functional abdominal pain disorders (FAPDs). The study uses secondary data analyses of a randomized controlled trial in which exposure-based online cognitive behavioral therapy (ICBT) was found superior to treatment as usual in decreasing gastrointestinal symptoms.

Methods

The ICBT included 10 weekly modules for children and 10 weekly modules for parents. Treatment as usual consisted of any medication, dietary adjustments, and healthcare visits that the participants engaged in during 10 weeks. All measures were self-assessed online by parents. Biweekly assessments of the Adult Responses to Children's Symptoms (ARCS), Protect and Monitor subscales, and the Pain Catastrophizing Scale, parental version (PCS-P) were included in univariate and multivariate growth models to test their mediating effect on the child's gastrointestinal symptoms assessed with the Pediatric Quality of Life Gastrointestinal Symptoms Scale (PedsQL).

Results

A total of 90 dyads of children with FAPDs and their parents were included in the study, of which 46 were randomized to ICBT and 44 to treatment as usual. The PCS-P was found to mediate change in the PedsQL ab = 0.639 (95% CI 0.020–2.331), while the ARCS Monitor ab = 0.472 (95% CI −1.002 to 2.547), and Protect ab = −0.151 (95% CI −1.455 to 0.674) were not mediators of change.

Conclusions

To target parental catastrophizing in ICBT for pediatric FAPDs is potentially important to reduce abdominal symptoms in children.
The nomogram predicting the early failure rate of the Pavlik harness for developmental dysplasia of the hip in infants under 6 months of age
Authors: Gou Pan , Gao Kai , Wang Xiaoting , Liu Xing
Published: October 2022

Background

The aim of our study was to develop a nomogram predicting the early failure rate of Pavlik harness in infants under 6 months of age with developmental dysplasia of the hip (DDH).

Methods

We retrospectively analyzed the clinical data of 227 patients (372 hips) with DDH who were treated with Pavlik harness at our institution from August 2019 to January 2022. Fifty-eight patients (102 hips) failed the Pavlik harness treatment, and 169 patients (270 hips) were successfully treated. Then, the independent risk factors for treatment failure were determined via univariate and multivariate logistic regression and used to generate the nomogram predicting the failure rate of the Pavlik harness.

Results

It was found that age at initial treatment (OR 1.031, 95% CI 1.022–1.040, P < 0.001), angle α (OR 0.723, 95% CI 0.671–0.779, P < 0.001), and concomitant deformity (OR 0.129, 95% CI 0.036–0.459, p = 0.002) were independent risk factors for treatment failure. The nomogram showed good discrimination [the area under the curve (AUC): 0.862], good calibration, and a net benefit in the range of probabilities between 5 and 90% according to the decision curve analysis.

Conclusion

This study successfully established the nomogram prediction model based on three independent risk factors. Due to the high level of predicting accuracy, this nomogram could be a useful resource for pediatric orthopedic surgeons to identify patients at major risk of Pavlik harness failure who might need more reliable treatments.
Maternal smoking during pregnancy and the risk of congenital urogenital malformations: A systematic review and meta-analysis
Authors: Zhang Qiang , Zhang Zhi-Cheng , He Xue-Yu , Liu Zhen-Min , Wei Guang-Hui , Liu Xing
Published: October 2022

Background

Investigations regarding the association between maternal smoking and specific urogenital teratogenesis exist. However, an integrated systematic review and meta-analysis studying the relationship by encompassing the whole urogenital system is essential.

Objective

Even though many studies about inborn urogenital malformations have been conducted, its etiologic factors and exact pathogenesis are still unclear. Our aim is to assess the risk of congenital urogenital malformations in offspring of smoking pregnant women.

Results

The meta-analysis, covering 41 case-control and 11 cohort studies, suggested that maternal smoking was associated with an increased risk of urogenital teratogenesis (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.04–1.23, p = 0.005), cryptorchidism (OR = 1.18, 95%CI: 1.12-1.24, p = 0.0001), hypospadias (OR = 1.16, 95%CI: 1.01-1.33, p = 0.039), and kidney malformations (OR = 1.30, 95%CI: 1.14-1.48, p = 0.0001). Moreover, paternal smoking during the mother’s pregnancy was also significantly associated (OR = 1.26, 95%CI: 1.03-1.55, p = 0.028). The association between smoking > 10 cigarettes/day was evident but was not significant (OR = 1.24, 95%CI:0.81-1.88, p = 0.323).

Conclusion

Our results showed that maternal smoking during pregnancy increased the risk of congenital urogenital malformations. In numerous epidemiological studies, maternal smoking during pregnancy has a significant role in fetal development. Therefore, quitting tobacco use may be an effective method for reducing the risk of congenital urogenital malformation in pregnant women.
Role of the multi-drug efflux systems on the baseline susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam in clinical isolates of non-carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa
Authors: Contreras-Gómez María José , Martinez José R. W. , Rivas Lina , Riquelme-Neira Roberto , Ugalde Juan A. , Wozniak Aniela , García Patricia , Munita José M. , Olivares-Pacheco Jorge , Alcalde-Rico Manuel
Published: October 2022

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is one of the pathogens that urgently needs new drugs and new alternatives for its control. The primary strategy to combat this bacterium is combining treatments of beta-lactam with a beta-lactamase inhibitor. The most used combinations against P. aeruginosa are ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T). Although mechanisms leading to CZA and C/T resistance have already been described, among which are the resistance-nodulation-division (RND) efflux pumps, the role that these extrusion systems may play in CZA, and C/T baseline susceptibility of clinical isolates remains unknown. For this purpose, 161 isolates of non-carbapenemase-producing (Non-CP) CRPA were selected, and susceptibility tests to CZA and C/T were performed in the presence and absence of the RND efflux pumps inhibitor, Phenylalanine-arginine β-naphthylamide (PAβN). In the absence of PAβN, C/T showed markedly higher activity against Non-CP-CRPA isolates than observed for CZA. These results were even more evident in isolates classified as extremely-drug resistant (XDR) or with difficult-to-treat resistance (DTR), where CZA decreased its activity up to 55.2% and 20.0%, respectively, whereas C/T did it up to 82.8% (XDR), and 73.3% (DTR). The presence of PAβN showed an increase in both CZA (37.6%) and C/T (44.6%) activity, and 25.5% of Non-CP-CRPA isolates increased their susceptibility to these two combined antibiotics. However, statistical analysis showed that only the C/T susceptibility of Non-CP-CRPA isolates was significantly increased. Although the contribution of RND activity to CZA and C/T baseline susceptibility was generally low (two-fold decrease of minimal inhibitory concentrations [MIC]), a more evident contribution was observed in a non-minor proportion of the Non-CP-CRPA isolates affected by PAβN [CZA: 25.4% (15/59); C/T: 30% (21/70)]. These isolates presented significantly higher MIC values for C/T. Therefore, we conclude that RND efflux pumps are participating in the phenomenon of baseline susceptibility to CZA and, even more, to C/T. However, the genomic diversity of clinical isolates is so great that deeper analyzes are necessary to determine which elements are directly involved in this phenomenon.
Therapeutic drug repositioning with special emphasis on neurodegenerative diseases: Threats and issues
Authors: Kakoti Bibhuti Bhusan , Bezbaruah Rajashri , Ahmed Nasima
Published: October 2022

Drug repositioning or repurposing is the process of discovering leading-edge indications for authorized or declined/abandoned molecules for use in different diseases. This approach revitalizes the traditional drug discovery method by revealing new therapeutic applications for existing drugs. There are numerous studies available that highlight the triumph of several drugs as repurposed therapeutics. For example, sildenafil to aspirin, thalidomide to adalimumab, and so on. Millions of people worldwide are affected by neurodegenerative diseases. According to a 2021 report, the Alzheimer’s disease Association estimates that 6.2 million Americans are detected with Alzheimer’s disease. By 2030, approximately 1.2 million people in the United States possibly acquire Parkinson’s disease. Drugs that act on a single molecular target benefit people suffering from neurodegenerative diseases. Current pharmacological approaches, on the other hand, are constrained in their capacity to unquestionably alter the course of the disease and provide patients with inadequate and momentary benefits. Drug repositioning–based approaches appear to be very pertinent, expense- and time-reducing strategies for the enhancement of medicinal opportunities for such diseases in the current era. Kinase inhibitors, for example, which were developed for various oncology indications, demonstrated significant neuroprotective effects in neurodegenerative diseases. This review expounds on the classical and recent examples of drug repositioning at various stages of drug development, with a special focus on neurodegenerative disorders and the aspects of threats and issues viz. the regulatory, scientific, and economic aspects.
Maintained anxiolytic effects of cannabidiol after treatment discontinuation in healthcare workers during the COVID-19 pandemic
Authors: Souza José Diogo S. , Zuardi Antonio W. , Guimarães Francisco S. , Osório Flávia de Lima , Loureiro Sonia Regina , Campos Alline Cristina , Hallak Jaime E. C. , Dos Santos Rafael G. , Machado Silveira Isabella Lara , Pereira-Lima Karina , Pacheco Julia Cozar , Ushirohira Juliana Mayumi , Ferreira Rafael Rinaldi , Costa Karla Cristinne Mancini , Scomparin Davi Silveira , Scarante Franciele Franco , Pires-Dos-Santos Isabela , Mechoulam Raphael , Kapczinski Flávio , Fonseca Benedito A. L. , Esposito Danillo L. A. , Andraus Maristela Haddad , Crippa José Alexandre S.
Published: October 2022

Objective: To assess whether the effects of oral administration of 300 mg of Cannabidiol (CBD) for 28 days on mental health are maintained for a period after the medication discontinuation.

Methods: This is a 3-month follow-up observational and clinical trial study. The data were obtained from two studies performed simultaneously by the same team in the same period and region with Brazilian frontline healthcare workers during the COVID-19 pandemic. Scales to assess emotional symptoms were applied weekly, in the first month, and at weeks eight and 12.

Results: The primary outcome was that, compared to the control group, a significant reduction in General Anxiety Disorder-7 Questionnaire (GAD-7) from baseline values was observed in the CBD group on weeks two, four, and eight (Within-Subjects Contrasts, time-group interactions: F1-125 = 7.67; p = 0.006; ηp2 = 0.06; F1-125 = 6.58; p = 0.01; ηp2 = 0.05; F1-125 = 4.28; p = 0.04; ηp2 = 0.03, respectively) after the end of the treatment.

Conclusions: The anxiolytic effects of CBD in frontline health care professionals during the COVID-19 pandemic were maintained up to 1 month after the treatment discontinuation, suggesting a persistent decrease in anxiety in this group in the real world. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings and weigh the benefits of CBD therapy against potential undesired or adverse effects.
A bibliometric and scientific knowledge map study of the drug therapies for asthma-related study from 1982 to 2021
Authors: Zhen Gao , Yingying Liu , Weifang Xu , Jingcheng Dong
Published: October 2022

Objective: Asthma drug research has been increasing yearly, and its clinical application value has increasingly attracted attention. This study aimed to analyze the development status, research hotspots, research frontiers, and future development trends of the research works on drugs for patients with asthma, especially severe asthma.

Methods: Asthma drug-related articles published between 1982 and 2021 were retrieved from the Web of Science Core Collection (WOSCC) database, and only articles published in English were included. CiteSpace and VOSviewer software were utilized to conduct collaborative network analysis of countries/regions, institutions, keywords, and co-citation analysis of references.

Results: A total of 3,234 asthma drug-related eligible articles were included. The United States was in a leading position, and Karolinska Institute (Sweden) was the most active institution. The most prolific journal in this field was Journal of Asthma, and the most cited journal was Journal of Allergy and Clinical Immunology. Keyword co-occurrence studies suggested that the current hotspots and frontiers were as follows: ① asthma: fully revealing the potential of existing conventional asthma drugs, determining the best drug delivery system, and indicating the best combination. To continue to explore potential targets for severe asthma or other phenotypes. Inhaled glucocorticoids and budesonide are still one of the important aspects of current asthma drug research and ② severe asthma: the research and development of new drugs, especially monoclonal antibodies including omalizumab, mepolizumab, and benralizumab to improve asthma control and drug safety, have become a research hotspot in recent years, highlighting the importance of “target” selection.

Conclusion: This study demonstrates the global research hotspots and trends of the research works on drugs for patients with asthma/severe asthma. It can help scholars quickly understand the current status and hotspots of research in this field.
Combined inhibition of PARP and EZH2 for cancer treatment: Current status, opportunities, and challenges
Authors: Zhang Xi , Huo Xiao , Guo Hongyan , Xue Lixiang
Published: October 2022

Tumors with BRCA1/2 mutations or homologous recombination repair defects are sensitive to PARP inhibitors through the mechanism of synthetic lethality. Several PARP inhibitors are currently approved for ovarian, breast and pancreatic cancer in clinical practice. However, more than 40% of patients with BRCA1/2 mutations are insensitive to PARP inhibitors, which has aroused attention to the mechanism of PARP resistance and sensitization schemes. PARP inhibitor resistance is related to homologous recombination repair, stability of DNA replication forks, PARylation and epigenetic modification. Studies on epigenetics have become the hotspots of research on PARP inhibitor resistance. As an important epigenetic regulator of transcription mediated by histone methylation, EZH2 interacts with PARP through DNA homologous recombination, DNA replication, posttranslational modification, tumor immunity and other aspects. EZH2 inhibitors have been just shifting from the bench to the bedside, but the combination scheme in cancer therapy has not been fully explored yet. Recently, a revolutionary drug design combining PARP inhibitors and EZH2 inhibitors based on PROTAC techniques has shed light on the resolution of PARP inhibitor resistance. This review summarizes the interactions between EZH2 and PARP, suggests the potential PARP inhibitor sensitization effect of EZH2 inhibitors, and further discusses the potential populations that benefit from the combination of EZH2 inhibitors and PARP inhibitors.
Adverse reaction signals mining and hemorrhagic signals comparison of ticagrelor and clopidogrel: A pharmacovigilance study based on FAERS
Authors: Tang Shu , Wu Zhanshen , Xu Liqing , Wen Qiang , Zhang Xiaojian
Published: October 2022

Background: Ticagrelor and clopidogrel are commonly used antiplatelet agents, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to provide a reference for safe and reasonable clinical use.

Methods: Data were collected in FAERS from 2012 Q1 to 2022 Q2 for data cleaning. We used system organ classes (SOCs) and prefer terms (PTs) from the Medical Dictionary of Regulatory Activity (MedDRA version 25.1). Adverse event reports were retrieved at the PT level. Adverse reaction (ADR) signals of ticagrelor and clopidogrel were mined by calculating reporting odds ratios (ROR), proportional reporting ratios (PRR), information component (IC) and empirical Bayesian geometric mean (EBGM). After that, further analysis of the hemorrhagic signals and their clinical information were performed.

Results: The number of ADR reports where the primary suspect (PS) drugs were 15,133 for ticagrelor and 23,860 for clopidogrel. Significant ADR signals were identified by the SOC analysis for ticagrelor including cardiac disorders (ROR 4.87, PRR 4.46), respiratory disorders (ROR 2.45, PRR 2.28), and vascular disorders (ROR 2.22, PRR 2.16). Clopidogrel included blood disorders (ROR 2.86, PRR 2.77), vascular disorders (ROR 2.71, PRR 2.61), and cardiac disorders (ROR 2.29, PRR 2.22). At the PT level, the more frequent ADR signals for ticagrelor were dyspnoea, contusion, and haemorrhage, while clopidogrel were gastrointestinal haemorrhage, anaemia, and drug interaction. The hemorrhagic signals of both were mainly focused on the SOC level of gastrointestinal disorders, injury disorders and vascular disorders and nervous system disorders. The death and life-threatening rate of ticagrelor was 7.76 percentage higher than that of clopidogrel.

Conclusion: Clinicians need to pay attention to not only common ADRs but also be alert to new ADR signals when choosing to use ticagrelor and clopidogrel. This study provides a reference for the reasonable and safe clinical use of ticagrelor and clopidogrel.
Efficacy and safety of eight types Salvia miltiorrhiza injections in the treatment of unstable angina pectoris: A network meta-analysis
Authors: Li Mingxuan , Li Hongdian , Liu Hongxu , Lai Xiaolei , Xing Wenlong
Published: October 2022

Background:Salvia miltiorrhiza Bunge. [Lamiaceae, danshen] injection classes (SMIC) is widely used in the treatment of unstable angina (UA). However, it is uncertain which SMIC is more effective in terms of UA efficacy. The purpose of this Network Meta-analysis (NMA) was to compare the treatment effects of various SMIC to determine the best SMIC for the treatment of UA.

Methods: The China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), Chinese Biomedical Literature Database (CBM), PubMed, Web of Science, and Cochrane Library databases were searched to screen randomized controlled trials (RCTs) of SMIC for UA. The search time frame was all from the establishment of the database to May 2022. RevMan 5.3 and Stata 14.0 software were used for NMA.

Results: A total of 148 studies including 14,979 patients, including 7,584 cases in the experimental group and 7,395 cases in the control group were included, and eight SMIC were extracted, namely:Danshen injection, Fufang Danshen injection, Guanxinning injection, Danshenchuanxiongqin injection, Danhong injection, Danshentong IIA Huangsuanna injection, Shenxiong Putaotang injection, and Danshenduofensuanyan injection. The results of NMA showed that, in terms of total effective rate, Shenxiong Putaotang injection and Danshenchuanxiongqin injection have the advantage; In terms of ECG efficiency, Danshentong IIA Huangsuanna injection and Danshen injection have an advantage; Danshenchuanxiongqin injection and Danshenduofensuanyan injection were more effective than other SMIC in improving angina pectoris attacks; Shenxiong Putaotang injection has an advantage in improving hs-CRP; Shenxiong Putaotang injection and Danshentong IIA Huangsuanna injection have advantages in improving TC and TG, respectively.

Conclusion: The eight SMIC included in the current study were effective in treating UA, Shenxiong Putaotang injection and Danshentong IIA Huangsuanna injection were both superior in improving all outcome indicators. However, there is still a need for larger samples and high-quality randomized controlled trials for more refined comparisons of various SMIC.

Systematic Review Registration: [PROSPERO], identifier [CRD42022350872]
Comprehensive analysis of cuproptosis in immune response and prognosis of osteosarcoma
Authors: Li Mingzhe , Song Qiang , Bai Yunfeng , Hua Feng , Wu Tao , Liu Jun
Published: October 2022

Copper-induced cell death, a form of apoptosis, has been extensively investigated in human diseases. Recent studies on the mechanisms underlying copper-induced cell death have provided innovative insights into copper-related toxicity in cells, and this form of programmed cell death was termed cuproptosis. Herein, we conducted a comprehensive analysis to determine the specific role of cuproptosis in osteosarcoma. Using consensus clustering analysis, patients with osteosarcoma from the TARGET database were classified into subgroups with distinct cuproptosis-based molecular patterns. Accordingly, these patients displayed diverse clinicopathological features, survival outcomes, tumor microenvironment (TME) characteristics, immune-related scores, and therapeutic responses. Furthermore, we constructed a cuproptosis-based risk signature and nomogram, as well as developed a cuproptosis score for improved patient characterization. The prognostic model and cuproptosis score were well validated and confirmed to efficiently distinguish high- and low-risk patients, thereby affording great predictive value. Finally, we verified the abnormal expression of prognostic CUG in OS patients by immunohistochemistry. In conclusion, we suggest that cuproptosis may play an important role in regulating the tumor microenvironment features, tumor progression and the long-term prognosis of osteosarcoma.
Dupilumab efficacy and safety in patients with moderate to severe asthma: A systematic review and meta-analysis
Authors: Zaazouee Mohamed Sayed , Alwarraqi Asmaa Gomaa , Mohammed Yasmine Adel , Badheeb Mohamed A. , Farhat Abdullah Mohamed , Eleyan Mohammed , Morad Afnan , Zeid Marwa Abdel-Aziz , Mohamed Aya Shaban , AbuEl-Enien Hazem , Abdelalim Ahmed , Elsnhory Ahmed Bostamy , Hrizat Yasmin S. M. , Altahir Nagat Taha , Atef Doaa , Elshanbary Alaa Ahmed , Alsharif Khalaf F. , Alzahrani Khalid J. , Algahtani Mohammad , Theyab Abdulrahman , Hawsawi Yousef M. , Aldarmahi Ahmed A. , Abdel-Daim Mohamed M.
Published: October 2022

Background: Dupilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-4 receptor and inhibits the signaling of IL-4 and IL-13. It is approved for treating asthma and other type-2 inflammatory diseases. There is a conflict in the literature regarding the safety and efficacy of dupilumab. Thus, we aimed to assess the safety and efficacy of dupilumab in patients with moderate to severe asthma.

Methods: Six databases (PubMed, Embase, Scopus, Web of Science, Cochrane library, and clinicaltrials.gov registry) were searched until January 2022. We included randomized controlled trials that compared dupilumab with the placebo in moderate to severe asthma patients. We extracted the data at 12 and 24 weeks and analyzed them using review manager 5.4.

Findings: Thirteen trials were included. Dupilumab significantly improved the forced expiratory volume in 1 s, asthma control questionnaire score, the fraction of exhaled nitric oxide level, and immunoglobulin E level at 12 and 24 weeks (p < 0.05). However, it was associated with increased blood eosinophils at 12 and 24 weeks. Dupilumab was generally a safe agent for asthmatic patients. It showed no significant difference compared with the placebo regarding most adverse events.

Conclusion: Dupilumab improves pulmonary function and reduces local and systemic inflammatory markers with minimal adverse events in patients with moderate to severe asthma.