bluuebunny/crossref_metadata_2025 huggingface dataset:
Human amniotic membrane application in oral surgery—An ex vivo pilot study
Authors: Odet Stéphane , Solecki Lauriana , Meyer Christophe , Weber Elise , Chatelain Brice , Euvrard Edouard , Barrabé Aude , Gualdi Thomas , Parmentier Anne-Laure , Tatu Laurent , Pouthier Fabienne , Louvrier Aurélien , Gindraux Florelle
Published: October 2022

Objectives: The purpose of this pilot porcine study was to explore and illustrate the surgical application of human amniotic membrane (hAM) in an ex vivo model of medication-related osteonecrosis of the jaw (MRONJ).

Material and methods: Five oral and maxillofacial surgeons participated to this study. MRONJ was simulated on porcine mandible specimens. hAM was applied using four different techniques: implantation with complete coverage, implantation with partial coverage, apposition and covering graft material. At the same time, the surgeons evaluated how well the hAM handled and its physical properties during the surgery.

Results: Surgeons found that hAM had suitable mechanical properties, as it was easy to detach from the support, handle, bind to the defect and bury. hAM was also found to be strong and stable. The “implantation with complete coverage” and “implantation with partial coverage” techniques were the preferred choices for the MRONJ indication.

Conclusion: This study shows that hAM is a graft material with suitable properties for oral surgery. It is preferable to use it buried under the gingiva with sutures above it, which increases its stability. This technical note aims to educate surgeons and provide them with details about the handling of hAM in oral surgery.

Clinical relevance: Two surgical techniques for hAM application in MRONJ were identified and illustrated. hAM handling and physical properties during surgery were reported.
Are we ready for the revision of the 14-day rule? Implications from Chinese legislations guiding human embryo and embryoid research
Authors: Xue Yang , Shang Lijun
Published: October 2022

The ISSCR recently released new guidelines that relaxed the 14-day rule taking away the tough barrier, and this has rekindled relevant ethical controversies and posed a fresh set of challenges to each nation’s legislations and policies directly or indirectly. To understand its broad implications and the variation and impact of China’s relevant national policies, we reviewed and evaluated Chinese laws, administrative regulations, departmental rules, and normative documents on fundamental and preclinical research involving human embryos from 1985 to 2022 in this paper. We have historically examined whether these regulations, including a 14-day rule, had restrictions on human embryo research, and whether and how these policies affected human embryo and embryoid research in China. We also discussed and assessed the backdrop in which China has endeavored to handle such as the need for expanding debates among justice practice, academia, and the public, and the shifting external environment influenced by fast-developing science and technology and people’s culture and religions. In general, Chinese society commonly opposes giving embryos or fetuses the legal status of humans, presumably due to the Chinese public not seeming to have any strong religious beliefs regarding the embryo. On this basis, they do not strongly oppose the potential expansion of the 14-day rule. After the guidelines to strengthen governance over ethics in science, and technology were released by the Chinese government in 2022, Chinese policymakers have incorporated bioethics into the national strategic goals using a “People-Centered” approach to develop and promote an ecological civilization. Specifically, China follows the “precautionary principle” based on ethical priority as it believes that if scientific research carries any potential technological and moral risks on which no social ethical consensus has been attained, there would be a need to impose oversight for prevention and precaution. At the same time, China has adopted a hybrid legislative model of legislation and ethical regulations with criminal, civil and administrative sanctions and a 14-day limit specified within its national hESCs guidelines. This would certainly be a useful example for other countries to use when considering the possibility of developing a comprehensive, credible and sustainable regulatory framework.
The new mechanism of cognitive decline induced by hypertension: High homocysteine-mediated aberrant DNA methylation
Authors: Wan Chong , Zong Rui-Yi , Chen Xing-Shu
Published: October 2022

The prevalence and severity of hypertension-induced cognitive impairment increase with the prolonging of hypertension. The mechanisms of cognitive impairment induced by hypertension primarily include cerebral blood flow perfusion imbalance, white and gray matter injury with blood–brain barrier disruption, neuroinflammation and amyloid-beta deposition, genetic polymorphisms and variants, and instability of blood pressure. High homocysteine (HHcy) is an independent risk factor for hypertension that also increases the risk of developing early cognitive impairment. Homocysteine (Hcy) levels increase in patients with cognitive impairment induced by hypertension. This review summarizes a new mechanism whereby HHcy-mediated aberrant DNA methylation and exacerbate hypertension. It involves changes in Hcy-dependent DNA methylation products, such as methionine adenosyltransferase, DNA methyltransferases, S-adenosylmethionine, S-adenosylhomocysteine, and methylenetetrahydrofolate reductase (MTHFR). The mechanism also involves DNA methylation changes in the genes of hypertension patients, such as brain-derived neurotrophic factor, apolipoprotein E4, and estrogen receptor alpha, which contribute to learning, memory, and attention deficits. Studies have shown that methionine (Met) induces hypertension in mice. Moreover, DNA hypermethylation leads to cognitive behavioral changes alongside oligodendroglial and/or myelin deficits in Met-induced mice. Taken together, these studies demonstrate that DNA methylation regulates cognitive dysfunction in patients with hypertension. A better understanding of the function and mechanism underlying the effect of Hcy-dependent DNA methylation on hypertension-induced cognitive impairment will be valuable for early diagnosis, interventions, and prevention of further cognitive defects induced by hypertension.
Leveraging the potential of synthetic text for AI in mental healthcare
Authors: Ive Julia
Published: October 2022

In today’s world it seems fair to say that extensive digital data sharing is the price we pay for the technological advances we have seen achieved as a result of AI systems analysing large quantities of data in a relatively short time. Where such AI is used in the realm of mental health, this data sharing poses additional challenges not just due to the sensitive nature of the data itself but also the potential vulnerability of the data donors themselves should there be a cybersecurity data breach. To address the problem, the AI community proposes to use synthetic text preserving only the salient properties of the original. Such text has potential to fill gaps in the textual data availability (e.g., rare conditions or under-represented groups) while reducing exposure. Our perspective piece is aimed to demystify the process of generating synthetic text, explain its algorithmic and ethical challenges, especially for the mental health domain, as well as most promising ways of overcoming them. We aim to promote better understanding and as a result acceptability of synthetic text outside the research community.
Aroclor 1254 induced inhibitory effects on osteoblast differentiation in murine MC3T3-E1 cells through oxidative stress
Authors: Chen Yu , Cai Yuwei , Chen Chunxiang , Li Mengting , Lu Lingdan , Yu Zhongxiang , Wang Shuqiang , Fang Lei , Xu Shengming
Published: October 2022

This study aimed to evaluate the osteotoxicity of polychlorinated biphenyls in murine osteoblastic MC3T3-E1 cells, and to explore the underlying mechanism focused on oxidative stress. The cells were exposed to Aroclor 1254 at concentrations of 2.5-20 µmol/L, and then cell viability, oxidative stress, intracellular calcium concentration, osteocalcin content, and calcium nodules formation were measured. Aroclor 1254 reduced cell viability and induced overproduction of intracellular reactive oxygen species in a dose-dependent manner. Activity of superoxide dismutase was decreased, and malondialdehyde content was promoted after exposure. Moreover, inhibitory effects of Aroclor 1254 on calcium metabolism and mineralization of osteoblasts were observed, as indicated by reduction of the intracellular calcium concentration, osteocalcin content, and modules formation rate. The decreased expression of osteocalcin, alkaline phosphatase, bone sialoprotein, and transient receptor potential vanilloid 6 further confirmed the impairment of Aroclor 1254 on calcium homeostasis and osteoblast differentiation. Addition of the antioxidant N-acetyl-L-cysteine partially restored the inhibitory effects on calcium metabolism and mineralization. In general, Aroclor 1254 exposure reduces calcium homeostasis, osteoblast differentiation and bone formation, and oxidative stress plays a vital role in the underlying molecular mechanism of osteotoxicity.
Attitudes of Australian dermatologists on the use of genetic testing: A cross-sectional survey with a focus on melanoma
Authors: Primiero Clare A. , Baker Amy M. , Wallingford Courtney K. , Maas Ellie J. , Yanes Tatiane , Fowles Lindsay , Janda Monika , Young Mary-Anne , Nisselle Amy , Terrill Bronwyn , Lodge Jason M. , Tiller Jane M. , Lacaze Paul , Andersen Hayley , McErlean Gemma , Turbitt Erin , Soyer H. Peter , McInerney-Leo Aideen M.
Published: October 2022

Background:Melanoma genetic testing reportedly increases preventative behaviour without causing psychological harm. Genetic testing for familial melanoma risk is now available, yet little is known about dermatologists’ perceptions regarding the utility of testing and genetic testing ordering behaviours.

Objectives:To survey Australasian Dermatologists on the perceived utility of genetic testing, current use in practice, as well as their confidence and preferences for the delivery of genomics education.

Methods:A 37-item survey, based on previously validated instruments, was sent to accredited members of the Australasian College of Dermatologists in March 2021. Quantitative items were analysed statistically, with one open-ended question analysed qualitatively.Results:The response rate was 56% (256/461), with 60% (153/253) of respondents between 11 and 30 years post-graduation. While 44% (112/252) of respondents agreed, or strongly agreed, that genetic testing was relevant to their practice today, relevance to future practice was reported significantly higher at 84% (212/251) (t =-9.82,p< 0.001). Ninety three percent (235/254) of respondents reported rarely or never ordering genetic testing. Dermatologists who viewed genetic testing as relevant to current practice were more likely to have discussed (p< 0.001) and/or offered testing (p< 0.001). Respondents indicated high confidence in discussing family history of melanoma, but lower confidence in ordering genetic tests and interpreting results. Eighty four percent (207/247) believed that genetic testing could negatively impact life insurance, while only 26% (63/244) were aware of the moratorium on using genetic test results in underwriting in Australia. A minority (22%, 55/254) reported prior continuing education in genetics. Face-to-face courses were the preferred learning modality for upskilling.

Conclusion:Australian Dermatologists widely recognise the relevance of genetic testing to future practice, yet few currently order genetic tests. Future educational interventions could focus on how to order appropriate genetic tests and interpret results, as well as potential implications on insurance.
New-onset dermatomyositis following COVID-19: A case report
Authors: Shimizu Hiroshi , Matsumoto Haruki , Sasajima Tomomi , Suzuki Tomohiro , Okubo Yoshinori , Fujita Yuya , Temmoku Jumpei , Yoshida Shuhei , Asano Tomoyuki , Ohira Hiromasa , Ejiri Yutaka , Migita Kiyoshi
Published: October 2022

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most of the infected individuals have recovered without complications, but a few patients develop multiple organ involvements. Previous reports suggest an association between COVID-19 and various inflammatory myopathies, in addition to autoimmune diseases. COVID-19 has been known to exacerbate preexisting autoimmune diseases and trigger various autoantibodies and autoimmune disease occurrence. Here we report a case of complicated COVID-19 with anti-synthetase autoantibodies (ASSs) presenting with skin rash, muscle weakness, and interstitial lung disease (ILD) and subsequently diagnosed with dermatomyositis (DM). A 47-year-old Japanese male patient without any previous history of illness, including autoimmune diseases, presented with a high fever, sore throat, and cough. Oropharyngeal swab for SARS-Cov-2 polymerase chain reaction tested positive. He was isolated at home and did not require hospitalization. However, his respiratory symptoms continued, and he was treated with prednisolone (20 mg/day) for 14 days due to the newly developing interstitial shadows over the lower lobes of both lungs. These pulmonary manifestations remitted within a week. He presented with face edema and myalgia 4 weeks later when he was off corticosteroids. Subsequently, he presented with face erythema, V-neck skin rash, low-grade fever, and exertional dyspnea. High-resolution computed tomography of the chest showed ILD. Biochemical analysis revealed creatine kinase and aldolase elevations, in addition to transaminases. Anti-aminoacyl tRNA synthetase (ARS) was detected using an enzyme-linked immunosorbent assay (170.9 U/mL) (MESACUP™ (Medical & Biological Laboratories, Japan), and the tRNA component was identified as anti-PL-7 and anti-Ro-52 antibodies using an immunoblot assay [EUROLINE Myositis Antigens Profile 3 (IgG), Euroimmun, Lübeck,Germany]. The patient was diagnosed with DM, especially anti- synthase antibody syndrome based on the presence of myositis-specific antibodies, clinical features, and pathological findings. The present case suggests that COVID-19 may have contributed to the production of anti-synthetase antibodies (ASAs) and the development of de novo DM. Our case highlights the importance of the assessment of patients who present with inflammatory myopathy post-COVID-19 and appropriate diagnostic work-up, including ASAs, against the clinical features that mimic DM after post-COVID-19.
The role of the complement system in primary membranous nephropathy: A narrative review in the era of new therapeutic targets
Authors: So Benjamin Y. F. , Chan Gary C. W. , Yap Desmond Y. H. , Chan Tak Mao
Published: October 2022

Primary membranous nephropathy (MN) is an important cause of nephrotic syndrome and chronic kidney disease (CKD) in the adult population. Although the discovery of different autoantibodies against glomerular/podocytic antigens have highlighted the role of B cells in the pathogenesis of MN, suboptimal response or even resistance to B cell-directed therapies occurs, suggesting that other pathophysiological mechanisms are involved in mediating podocyte injury. The complement system plays an important role in the innate immune response to infection, and dysregulation of the complement system has been observed in various kidney diseases. There is compelling evidence of complement cascade activation in primary MN, with the mannose-binding lectin (MBL) and alternative pathways particularly implicated. With appropriate validation, assays of complements and associated activation products could hold promise as adjunctive tools for non-invasive disease monitoring and prognostication. While there is growing interest to target the complement system in MN, there is concern regarding the risk of infection due to encapsulated organisms and high treatment costs, highlighting the need for clinical trials to identify patients most likely to benefit from complement-directed therapies.
Interaction of RARRES1 with ICAM1 modulates macrophages to suppress the progression of kidney renal clear cell carcinoma
Authors: Geng Xiaodong , Chi Kun , Liu Chao , Fu Zhangning , Wang Xu , Meng Liangliang , Wang Hanfeng , Cai Guangyan , Chen Xiangmei , Hong Quan
Published: October 2022

Background

RARRES1 is a tumor suppressor protein, and its expression is suppressed in various tumor cells. However, whether it participates in the immune response in kidney renal clear cell carcinoma (KIRC) is unknown, and the defined mechanism is not clear. Therefore, the mechanism of RARRES1 in KIRC is worthy of investigation.

Methods

We analysed the expression and function of RARRES1 with The Cancer Genome Atlas (TCGA) database. The Kaplan–Meier curve was adopted to estimate survival. RARRES1-correlated genes were obtained from the UALCAN database and subjected to Gene Ontology (GO) enrichment and protein–protein interaction (PPI) network analyses. The correlation analysis between tumor-infiltrating immune cells and selected genes were performed with TIMER database. We also investigated the possible function of RARRES1 in KIRC by coculturing Caki-1 cells with THP-1 cells. Immunofluorescence assay was performed to study the RARRES1 expression in difference grade KIRC tissues.

Results

The expression of RARRES1 was negatively correlated with survival in KIRC patients. The GO biological process term most significantly enriched with the RARRES1-correlated genes was regulation of cell adhesion. ICAM1, which exhibited a relatively highest correlation with RARRES1, is positively correlated with the infiltration level of macrophages. RARRES1 could enhance the expression of ICAM1 in Caki-1 cells and then induce the activation of M1 THP-1 cells to decrease the viability and induce the apoptosis of Caki-1 cells.

Conclusion

RARRES1 plays an antitumor role by promoting ICAM1 expression and inducing the activation of M1 macrophages. We offer insights into the molecular mechanism of KIRC and reveal a potential therapeutic target.
Study on the size effect of the secant modulus of rocks containing multiple parallel joints
Authors: Zhang Jing , Guo Wannian , Fu Yongzhi , Feng Yong , Wang Qingxia , Hu Gaojian , Wang Tao
Published: October 2022

The secant modulus of the rock reflects the stiffness of the rock and the ability to resist deformation. There are significant differences in the secant modulus of the rock due to the different numbers of joints in the rock and the change in rock size. Therefore, it is important to obtain effectively the secant modulus of rocks with the number of parallel joints for evaluating rock deformation. In this study, the method of regression analysis is used, and 10 sets of numerical plans are set up to discuss the influence of a number of parallel joints and rock size on the secant modulus. The results show that the secant modulus decreases with the increase in a number of parallel joints, and the curve is a power function. The secant modulus decreases when the rock size increases, and the curve is an exponential function. The characteristic secant modulus and characteristic size decrease with the increase in the number of parallel joints, and their curves are an exponential function. The specific forms of these relationships are given in the article. The establishment of these relationships realizes the prediction and calculation of the rock secant modulus with the number of parallel joints, which provides a guiding significance for the rock deformation analysis.
The role of APTX4870 peptide in reducing cellular inflammatory responses by inhibiting Mycobacterium tuberculosis-derived mycolic acid-induced cytotoxicity
Authors: Lin Xue , Jia Wei , Feng Gangning , Su Yajing , Kang Yuting , Zhang Chen , Liu Wenmiao , Lu Zhidong , Xue Di
Published: October 2022

Tuberculosis is a serious zoonotic disease caused by Mycobacterium tuberculosis (M.tb) and the M.tb complex. Mycolic acid is an extracellular carbohydrate polymer produced, secreted, and accumulated outside the cells of various Mycobacterium tuberculosis strains. Mycolic acid produced by Mycobacterium plays an important role in infection. However, there have been few reports on drugs that inhibit mycolic acid-induced cytotoxicity. The purpose of this study was to investigate the role of the panned peptide in Mycobacterium-derived mycolic acid (M.tb-MA)-induced cell injury. The heptapeptide (APTX4870) was isolated from various phage libraries using phage display (Ph.D-7, Ph.D-12, and Ph.D-C7C). The efficacy of APTX4870 against mycolic acid was demonstrated by evaluating clinical samples and conducting in vitro and Vivo. APTX4870 inhibited apoptosis, increased autophagy to decrease inflammation, and reduced M.tb-MA-induced lung damage. These findings suggest that this heptapeptide, which selectively targets M.tb-MA, might be exploited as a potential novel M.tb therapeutic treatment.
Phenotype-based drug screening: An in vivo strategy to classify and identify the chemical compounds modulating zebrafish M-cell regeneration
Authors: Kumari Ankita , Zeng Xin-An , Rahaman Abdul , Farooq Muhammad Adil , Huang Yanyan , Alee Mahafooj , Yao Runyu , Ali Murtaza , Khalifa Ibrahim , Badr Omnia
Published: October 2022

Several disease-modulatory FDA-approved drugs are being used in patients with neurodegenerative diseases. However, information on their toxicity-related profiles is very limited. Therefore, measurement of drug toxicity is essential to increase the knowledge of their side effects. This study aimed to identify compounds that can modulate M-cell regeneration by causing neuro-protection and -toxicity. Here, we developed a simple and efficient in vivo assay using Tg (hsp: Gal4FF62A; UAS: nfsB-mCherry) transgenic zebrafish larvae. Interestingly, via the phenotype-based drug screening approach, we rapidly investigated 1,260 compounds from the United States drug collection and validated these in large numbers, including 14 compounds, that were obstructing this regeneration process. Next, 4 FDA-approved drugs out of 14 compounds were selected as the lead hits for in silico analysis to clarify their binding patterns with PTEN and SOCS3 signaling due to their significant potential in the inhibition of axon regeneration. Molecular docking studies indicated good binding affinity of all 4 drugs with the respective signaling molecules. This may point to PTEN and SOCS3 as the signaling molecules responsible for reducing axon regeneration. Moreover, the acute effect of compounds in reducing M-cell regeneration delineated their toxic effect. In conclusion, our in vivo along with in silico screening strategy will promote the rapid translation of new therapeutics to improve knowledge of the toxicity profile of approved/non-approved drugs efficiently.
Osmotic gradients and transretinal water flow—a quantitative elemental microanalytical study of frozen hydrated chick eyes
Authors: Marshall Alan T. , Crewther Sheila G.
Published: October 2022

Optical clarity and efficient phototransduction are necessary for optimal vision, however, how the associated processes of osmoregulation and continuous fluid drainage across the whole eye are achieved remains relatively unexplored. Hence, we have employed elemental microanalysis of planed surfaces of light-adapted bulk frozen-hydrated chick eyes to determine the unique intracellular elemental localization, compositions, and hydration states that contribute to maintaining osmotic gradients and water flow from the vitreous, across the retina, retinal pigment epithelium (RPE), to choroid and sclera. As expected, the greatest difference in resultant osmotic concentration gradients, [calculated using the combined concentrations of sodium (Na) and potassium (K)] and tissue hydration [oxygen-defined water concentration], occurs in the outer retina and, in particular, in the RPE where the apical and basal membranes are characterized by numerous bioenergetically active, osmoregulating ion transport mechanisms, aquaporins, and chloride (Cl) channels. Our results also demonstrate that the high intracellular Na+and K+concentrations in the apical region of the RPE are partially derived from the melanosomes. The inclusion of the ubiquitous osmolyte taurine to the calculation of the osmotic gradients suggests a more gradual increase in the osmotic transport of water from the vitreous into the ganglion cell layer across the inner retina to the outer segments of the photoreceptor/apical RPE region where the water gradient increases rapidly towards the basal membrane. Thus transretinal water is likely to cross the apical membrane from the retina into the RPE cells down the Na+and K+derived osmotic concentration gradient and leave the RPE for the choroid across the basal membrane down the Cl−derived osmotic concentration gradient that is sustained by the well-described bioenergetically active RPE ion transporters and channels.
Efficacy and safety of sympathetic radiofrequency thermocoagulation in the treatment of cold hypersensitivity
Authors: Liao Yuefeng , Xu Chi , Xia Jianmei , Ni Huadong , Zhang Zhiqiang , Ni Chunjue
Published: October 2022

Background

Cold hypersensitivity (CH) is a sensation of cold in the limbs and (or) body of a patient in an environment that is not considered cold by unaffected people, or a strong feeling of cold at a relatively low temperature. However, the currently available treatments are limited and often unsatisfactory. This study aimed to evaluate the clinical efficacy and safety of the sympathetic radiofrequency thermocoagulation (RF-TC) technique in patients with CH disorder.

Methods

The study is a retrospective analysis. A total of 71 were entered into the final analysis and all patients underwent computed tomography-guided thoracic (lumbar) sympathetic nerve RF-TC on an elective basis. The values of terminal temperature (T) and perfusion index (PI) of patients before and after treatment were recorded. Patients were followed up clinically at regular intervals and their Visual Analog Scale (VAS) and Pittsburgh Sleep Quality Index (PSQI) scores were recorded to detect postoperative complications and assess patient satisfaction with the treatment.

Results

All patients completed the radiofrequency treatment. Compared with the preoperative period, VAS and PSQI scores were significantly lower at all postoperative time periods (P < 0.001). Patients had significantly higher postoperative terminal temperatures and perfusion indices on the right and left sides than before surgery (P < 0.001). The overall patient satisfaction score was 4 (3–5) at 3 years of postoperative follow-up. There were 20 recurrences (28.2%). The main postoperative complications were postoperative local pain and compensatory hyperhidrosis. No other adverse events or deaths were observed.

Conclusion

RF-TC for CH could be a feasible, effective, and safe treatment option to improve patients' symptoms of cold sensation. Yet, more researches are needed to verify this potentially efficient and standardized treatment.
A longitudinal study on associations of moderate-to-vigorous physical activity with plasma monounsaturated fatty acids in pregnancy
Authors: Xia Tong , Chen Liwei , Fei Zhe , Liu Xinyue , Dai Jin , Hinkle Stefanie N. , Zhu Yeyi , Wu Jing , Weir Natalie L. , Tsai Michael Y. , Zhang Cuilin
Published: October 2022

Background

Physical activity (PA) during pregnancy influences women and offspring’s health via fatty acids metabolism. However, studies on associations of PA with plasma monounsaturated fatty acids (MUFAs) across pregnancy are sparse. Thus, our study aimed to examine associations of PA with individual plasma phospholipid MUFAs throughout pregnancy in a prospective and longitudinal study in the United States (US).

Materials and methods

The study included 318 pregnant women from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons cohort. PA was measured four times: PA reported at 10–14 gestational weeks (GWs) representing PA in the past year, and at 15–26 GWs, 23–31 GWs, and 33–39 GWs representing PA since the last visit. Plasma phospholipid MUFAs were measured at the same four visits as the measurement of PA. Associations between moderate-to-vigorous PA (MVPA) and the total MUFAs and seven individual plasma phospholipid MUFAs (i.e., palmitoleic acid, 18:1n6-9 trans, 18:1n6c, cis-vaccenic acid, oleic acid, eicosenoic acid, and nervonic acid) were assessed at each visit using multivariable linear regression models adjusting for confounders.

Results

MVPA (hours/week) reported at 15–26 GWs representing MVPA since the last visit was positively associated with total MUFAs (% of total fatty acids) [adjusted β*102 (standard error (SE)*102) = 10.41 (3.19), P = 0.001] at 15–26 GWs. For individual MUFAs, MVPA reported at 15–26 GWs representing MVPA since the last visit was positively associated with oleic acid [adjusted β*102 (SE*102) = 8.56 (2.65), P = 0.001] and eicosenoic acid [adjusted β*102 (SE*102) = 0.55 (0.20), P = 0.01] at 15–26 GWs. MVPA reported at 23–31 GWs representing MVPA since the last visit was positively associated with palmitoleic acid [adjusted β*102 (SE*102) = 2.24 (0.64), P = 0.001] at 23–31 GWs. MVPA reported at 10–14 GWs and 33–39 GWs was not associated with total or individual MUFAs.

Conclusion

We found novel positive associations of MVPA with individual MUFAs, such as oleic acid, eicosenoic acid, and palmitoleic acid, during middle-to-late pregnancy. These findings suggest that MVPA represents a potentially modifiable factor for plasma individual MUFA levels during pregnancy.
Circulating syndecan-1 and glypican-4 predict 12-month survival in metastatic colorectal cancer patients
Authors: Muendlein Axel , Severgnini Luciano , Decker Thomas , Heinzle Christine , Leiherer Andreas , Geiger Kathrin , Drexel Heinz , Winder Thomas , Reimann Patrick , Mayer Frank , Nonnenbroich Christoph , Dechow Tobias
Published: October 2022

Cell surface syndecans and glypicans play important roles in the development and prognosis of colorectal cancer (CRC). Their soluble forms from proteoglycan shedding can be detected in blood and have been proposed as new prognostic biomarkers in several cancer entities. However, studies on circulating syndecan-1 (SDC1) and glypican-4 (GPC4) in CRC are limited. We, therefore, evaluated the impact of plasma SDC1 and GPC4 on the prognosis of metastatic (m)CRC patients. The present study included 93 patients with mCRC. The endpoints were progression-free survival (PFS) and overall survival (OS) at 12 months. SDC1 and GPC4 levels were measured in plasma using enzyme-linked immunosorbent assays. Plasma levels of SDC1 and GPC4 were significantly correlated. Significant correlations of these two markers were also found with carcinoembryonic antigen (CEA). Kaplan-Meier curve analyses indicated that PFS and OS probabilities significantly decreased with increasing levels of SDC1 and GPC4, respectively. Multivariable Cox regression analyses showed that both markers were significantly associated with PFS and OS independently from clinicopathological characteristics including CEA. Respective adjusted hazard ratios (HR) together with corresponding 95% confidence intervals for one standard deviation change of SDC1 were 1.32 [1.02-1.84] for PFS and 1.48 [1.01-2.15] for OS. Adjusted HRs [95% confidence intervals] of GPC4 were 1.42 [1.07-1.89] for PFS and 2.40 [1.51-3.81] for OS. Results from area under the receiver operating characteristic curve analyses suggest that GPC4 and SDC1 add additional prognostic values to CEA for OS. In conclusion, we showed significant associations of circulating SDC1 and GPC4 with poor survival of mCRC patients.
Prediction of axillary lymph node pathological complete response to neoadjuvant therapy using nomogram and machine learning methods
Authors: Zhou Tianyang , Yang Mengting , Wang Mijia , Han Linlin , Chen Hong , Wu Nan , Wang Shan , Wang Xinyi , Zhang Yuting , Cui Di , Jin Feng , Qin Pan , Wang Jia
Published: October 2022

Purpose

To determine the feasibility of predicting the rate of an axillary lymph node pathological complete response (apCR) using nomogram and machine learning methods.

Methods

A total of 247 patients with early breast cancer (eBC), who underwent neoadjuvant therapy (NAT) were included retrospectively. We compared pre- and post-NAT ultrasound information and calculated the maximum diameter change of the primary lesion (MDCPL): [(pre-NAT maximum diameter of primary lesion – post-NAT maximum diameter of preoperative primary lesion)/pre-NAT maximum diameter of primary lesion] and described the lymph node score (LNS) (1): unclear border (2), irregular morphology (3), absence of hilum (4), visible vascularity (5), cortical thickness, and (6) aspect ratio <2. Each description counted as 1 point. Logistic regression analyses were used to assess apCR independent predictors to create nomogram. The area under the curve (AUC) of the receiver operating characteristic curve as well as calibration curves were employed to assess the nomogram’s performance. In machine learning, data were trained and validated by random forest (RF) following Pycharm software and five-fold cross-validation analysis.

Results

The mean age of enrolled patients was 50.4 ± 10.2 years. MDCPL (odds ratio [OR], 1.013; 95% confidence interval [CI], 1.002–1.024; p=0.018), LNS changes (pre-NAT LNS – post-NAT LNS; OR, 2.790; 95% CI, 1.190–6.544; p=0.018), N stage (OR, 0.496; 95% CI, 0.269–0.915; p=0.025), and HER2 status (OR, 2.244; 95% CI, 1.147–4.392; p=0.018) were independent predictors of apCR. The AUCs of the nomogram were 0.74 (95% CI, 0.68–0.81) and 0.76 (95% CI, 0.63–0.90) for training and validation sets, respectively. In RF model, the maximum diameter of the primary lesion, axillary lymph node, and LNS in each cycle, estrogen receptor status, progesterone receptor status, HER2, Ki67, and T and N stages were included in the training set. The final validation set had an AUC value of 0.85 (95% CI, 0.74–0.87).

Conclusion

Both nomogram and machine learning methods can predict apCR well. Nomogram is simple and practical, and shows high operability. Machine learning makes better use of a patient’s clinicopathological information. These prediction models can assist surgeons in deciding on a reasonable strategy for axillary surgery.
Quality of life and function after rectal cancer surgery with and without sphincter preservation
Authors: Pappou Emmanouil P. , Temple Larissa K. , Patil Sujata , Smith J. Joshua , Wei Iris H. , Nash Garrett M. , Guillem José G. , Widmar Maria , Weiser Martin R. , Paty Philip B. , Schrag Deborah , Garcia-Aguilar Julio
Published: October 2022

Despite improvements in surgical techniques, functional outcomes and quality of life after therapy for rectal cancer remain suboptimal. We sought to prospectively evaluate the effect of bowel, bladder, and sexual functional outcomes on health-related quality of life (QOL) in patients with restorative versus non-restorative resections after rectal cancer surgery. A cohort of 211 patients with clinical stage I-III rectal cancer who underwent open surgery between 2006 and 2009 at Memorial Sloan Kettering were included. Subjects were asked to complete surveys preoperatively and at 6, 12, and 24 months after surgery. Validated instruments were used to measure QOL, bowel, bladder, and sexual function. Univariable and multivariable regression analyses evaluated predictors of 24- month QOL. In addition, longitudinal trends over the study period were evaluated using repeated measures models. In total, 180 patients (85%) completed at least 1 survey, and response rates at each time point were high (>70%). QOL was most impaired at 6 and 12 months and returned to baseline levels at 24 months. Among patients who underwent sphincter-preserving surgery (SPS; n=153 [85%]), overall bowel function at 24 months was significantly impaired and never returned to baseline. There were no differences in QOL at 24 months between patients who underwent SPS and those who did not (p=.29). Bowel function was correlated with QOL at 24 months (Pearson correlation,.41; p<.001). QOL among patients who have undergone SPS for rectal cancer is good despite poor function. Patients with ostomies are able to adjust to the functional changes and, overall, have good global QOL. Patients with low anastomoses had lower global QOL at 24 months than patients with permanent stomas. Our findings can help patients set expectations about function and quality of life after surgery for rectal cancer with and without a permanent stoma.
Gratitude among advanced cancer patients and their caregivers: The role of early palliative care
Authors: Borelli Eleonora , Bigi Sarah , Potenza Leonardo , Gilioli Fabio , Artioli Fabrizio , Porzio Giampiero , Porro Carlo Adolfo , Efficace Fabio , Bruera Eduardo , Luppi Mario , Bandieri Elena
Published: October 2022

Objective

A cancer diagnosis represents a unique trauma, given its life-threatening, multidimensional, and uncertain nature. Gratitude is a construct representing the emotional state that arises when individuals recognize that a benefit has been received as a result of someone else’s action or a spiritual entity’s intervention. Based on the positive psychological wellbeing, gratitude has been associated with improved health outcomes even in the disease setting. Thus, the models of care that foster gratitude should be adopted in the clinical context. This study aims to explore whether and how gratitude may originate in patients with advanced cancer and their caregivers undergoing early palliative care (EPC).

Methods

We analyzed 251 reports from 133 patients and 118 caregivers describing their clinical experience in two EPC units. The sources of gratitude were identified and ranked based on their frequencies. Words expressing gratitude and words referring to communication and spirituality were collected by means of the Linguistic Inquiry and Word Count software and correlated.

Results

In total, 123 (92.5%) of 133 patients’ and 97 (82.2%) of 118 caregivers’ reports, respectively, included explicit or implicit expressions of gratitude. Gratitude was associated specifically with successful physical symptom management, emotional support, improved attitude toward death, better information, humanity, and the familiar environment. The use of words of gratitude in patients’ reports was positively correlated with the use of words referring to communication (r = .215, p = .026) and spirituality (r = .612, p <.001).

Conclusion

Our results suggest that interventions within the EPC model based on doctor–patient–caregiver communication may allow patients and caregivers to experience a feeling of gratitude, and this may represent a resource to be exploited to improve their physical and psychosocial wellbeing.
A methodological and clinical approach to measured energy expenditure in the critically ill pediatric patient
Authors: Silva-Gburek Jaime , Zhu Paola Hong , Mansour Marwa , Walding David , Coss-Bu Jorge A.
Published: October 2022

The metabolic response to injury and stress is characterized initially by a decreased energy expenditure (Ebb phase) followed by an increased metabolic expenditure (Flow phase). Indirect calorimetry is a methodology utilized to measure energy expenditure and substrate utilization by measuring gas exchange in exhaled air and urinary nitrogen. The use of indirect calorimetry in critically ill patients requires precise equipment to obtain accurate measurements. The most recent guidelines suggested that measured energy expenditure by indirect calorimetry be used to determine energy requirements. This article reviews the methodological and clinical use of indirect calorimetry in critically ill pediatric patients.
Applying machine learning to the pharmacokinetic modeling of cyclosporine in adult renal transplant recipients: a multi-method comparison
Authors: Mao Junjun , Chen Yuhao , Xu Luyang , Chen Weihuang , Chen Biwen , Fang Zhuo , Qin Weiwei , Zhong Mingkang
Published: October 2022

Objective: The aim of this study was to identify the important factors affecting cyclosporine (CsA) blood concentration and estimate CsA concentration using seven different machine learning (ML) algorithms. We also assessed the predictability of established ML models and previously built population pharmacokinetic (popPK) model. Finally, the most suitable ML model and popPK model to guide precision dosing were determined.

Methods: In total, 3,407 whole-blood trough and peak concentrations of CsA were obtained from 183 patients who underwent initial renal transplantation. These samples were divided into model-building and evaluation sets. The model-building set was analyzed using seven different ML algorithms. The effects of potential covariates were evaluated using the least absolute shrinkage and selection operator algorithms. A separate evaluation set was used to assess the ability of all models to predict CsA blood concentration. R squared (R2) scores, median prediction error (MDPE), median absolute prediction error (MAPE), and the percentages of PE within 20% (F20) and 30% (F30) were calculated to assess the predictive performance of these models. In addition, previously built popPK model was included for comparison.

Results: Sixteen variables were selected as important covariates. Among ML models, the predictive performance of nonlinear-based ML models was superior to that of linear regression (MDPE: 3.27%, MAPE: 34.21%, F20: 30.63%, F30: 45.03%, R2 score: 0.68). The ML model built with the artificial neural network algorithm was considered the most suitable (MDPE: −0.039%, MAPE: 25.60%, F20: 39.35%, F30: 56.46%, R2 score: 0.75). Its performance was superior to that of the previously built popPK model (MDPE: 5.26%, MAPE: 29.22%, F20: 33.94%, F30: 51.22%, R2 score: 0.68). Furthermore, the application of the most suitable model and the popPK model in clinic showed that most dose regimen recommendations were reasonable.

Conclusion: The performance of these ML models indicate that a nonlinear relationship for covariates may help to improve model predictability. These results might facilitate the application of ML models in clinic, especially for patients with unstable status or during initial dose optimization.
The role of p53 in liver fibrosis
Authors: Yu Siyu , Ji Guang , Zhang Li
Published: October 2022

The tumor suppressor p53 is the central hub of a molecular network, which controls cell proliferation and death, and also plays an important role in the occurrence and development of liver fibrosis. The abundant post-translational processing and modification endow the functional diversity of p53. Considering the relationship between p53 and liver fibrosis, drug intervention targeting p53 or management of p53 regulation might be effective strategies to treat liver fibrosis. Here, we systematically discuss the regulation of p53 in different liver cells (hepatocytes, immune cells, HSCs, etc) and the role of p53 in the development of liver fibrosis, and propose possible interventions to prevent the pathogenic processes of liver fibrosis.
Total cannabidiol (CBD) concentrations and yields from traditional extraction methods: Percolation vs. maceration
Authors: Wilson Jason , Simpson Travis , Spelman Kevin
Published: October 2022

Medicinal plants have been valued for many generations due to their biosynthetic advantages generating pharmacologically active molecules. This is especially the case when it comes to cannabinoids from Cannabis. In these experiments we mimicked typical herbal home extractions and measured the yield of total decarboxylated CBD (“total CBD”) from percolations and macerations done at the common duration of 2 weeks in duplicate independent extractions. Analysis was performed by GC-FID on triplicate samples from each extraction. Results demonstrated a significant extraction superiority of percolation over maceration. Percolation extracted 80.1% of the total CBD in the hemp biomass as compared to the 2-week time point at 63.5% recovery. Our results demonstrate a significant increase in total CBD yield from percolation, as compared to maceration. Highest solvent recovery was also through percolation, but overall solvent recovery was fairly consistent with the maceration method, after pressing. Under these conditions of extracting lipophilic cannabidiol in 95% ethanol, these data demonstrate that percolation is significantly superior to maceration in total CBD yield. These observations will likely apply to the extraction of lipophilic constituents from other herbs and botanical medicines.
Artemisinin derivative DHA27 enhances the antibacterial effect of aminoglycosides against Pseudomonas aeruginosa by inhibiting mRNA expression of aminoglycoside-modifying enzymes
Authors: Wang Nuoyan , Chen Xuemin , Luo Jing , Deng Fei , Shi Fuguo , Wu Qin , Huang Yasi , Ouyang Qin , Qin Rongxin , Zhou Hong
Published: October 2022

Bacterial resistance is becoming increasingly serious, the present study aimed to investigate the mechanism of antibacterial sensitization effect of DHA27 combined with tobramycin in tobramycin-resistant Pseudomonas aeruginosa (PA). We found that DHA27 combined with aminoglycosides had an antibacterial sensitization effect on PA. Tobramycin, owing to its lower toxic and side effects, was selected to further study the molecular mechanism of drug combination. A sublethal-dose bacterial challenge/sepsis mouse model was established to study the protective effect of DHA27 plus tobramycin. Scanning electron microscopy was used to investigate whether DHA27 exerts the antibacterial sensitization effect by directly affecting bacterial morphology. The effect of DHA27 on daunorubicin accumulation in bacteria was studied, and quantitative reverse transcription PCR was used to study the effect of DHA27 plus tobramycin on 16S rRNA methyltransferase and aminoglycoside-modifying enzyme mRNA expression. Twenty clinical isolates of PA were found to be tobramycin resistant; DHA27 plus tobramycin had a significant antibacterial sensitization effect on many of these resistant strains. DHA27 plus tobramycin reduced the bacterial load in the spleen and lungs of sepsis model mice and levels of proinflammatory cytokines interleukin-1β (IL-1β) and interferon-γ (IFN-γ). DHA27 plus tobramycin significantly inhibited the mRNA expression of aminoglycoside-modifying enzymes in bacteria. DHA27 combined with AGs had an antibacterial sensitization effect on PA; the molecular mechanism underlying this effect is closely related to the inhibition of the mRNA expression of aminoglycoside-modifying enzymes, especially aac(3)-II.