bluuebunny/crossref_metadata_2025 huggingface dataset:
A framework for a net environmental benefit analysis based comparative assessment of decommissioning options for anthropogenic subsea structures: A North Sea case study
Authors: Nicolette Joseph P. , Nelson Nicholas A. , Rockel Michael K. , Rockel Mark L. , Testoff Alex N. , Johnson Larry L. , Williamson Laura D. , Todd Victoria L. G.
Published: January 2023

Taxpayers and operators worldwide have significant current liabilities associated with decommissioning of offshore Oil & Gas (O&G) assets. Consequently, decommissioning is at the forefront of industrial, governmental, and non-governmental agendas. Decommissioning is a highly complex activity with health, safety, environmental, social, economic, and technical implications. Increasing scientific evidence supports that manmade subsea structures create hard, artificial reef habitats that provide ecological and social benefits to society. Given the significant uncertainty regarding how subsea structures should be retired at the end of their operational lifetimes, it is necessary for governments, taxpayers, and operators to understand the risks and benefits associated with potential decommissioning options. Currently, the North Sea decommissioning process is based on the policies and direction of the Oslo and Paris Convention’s (OSPAR) Decision 98/3 and follow comparative assessment (CA) multiple-criteria decision analysis (MCDA) guidelines to determine the best overall strategy for decommissioning subsea structures; however, CA MCDA processes can be biased, ambiguous, difficult to use, interpret, and replicate, and limited in their consideration of multigenerational benefits. Consequently, to assist decision-makers in understanding and evaluating options and associated benefits for decommissioning subsea structures, this study adapted the net environmental benefit analysis (NEBA) framework to supplement and strengthen the CA process for evaluating decommissioning options for offshore O&G facilities. The net environmental benefit analysis based comparative assessment (NEBA-CA) framework is presented that addresses the growing need for a practical, quantitative, scientifically robust, defendable, and transparent MCDA approach to determine optimized decommissioning strategies for subsea assets. Increased transparency in CAs will provide an additional layer of credibility with regulators and society. The approach is data driven and a desktop analysis mainly relying on existing data. Using a North Sea case study, this work demonstrates the ability of NEBA-CA to resolve inherent complexity in comparing decommissioning options, thereby supporting operators in working with regulators to decommission assets in a way that maximizes ecosystem service benefits to society while managing site-related risks and costs. The NEBA-CA framework supplements and strengthens the standard CA process by 1) incorporating quantified metrics including multigenerational ecosystem service benefits and risks, 2) excluding front ranking (scoring) or weighting of metrics, and 3) providing consistent graphical displays to support visual differentiation of options and metrics.
Evaporation-induced self-assembly of gold nanorods on a hydrophobic substrate for surface enhanced Raman spectroscopy applications
Authors: Usman Muhammad , Ishafaq M. U. U. , Muhammad Zahir , Ali Wajid , Dastgeer Ghulam , Zhang Xiao , Wang Liang
Published: January 2023

The controllable assembly of plasmonic nanoparticles has developed as one of the most significant approaches for surface enhanced Raman spectroscopy (SERS) applications. This study developed a simple approach to improve a large-scale ordered assembly of gold nanorods (GNRs) by controlling the droplet evaporation mode on hydrophobic substrates. The hydrophobic substrate was efficiently produced by spin coating the silicone oil onto the glass slides and annealing them. The analyte molecule rhodamine (R6G) was employed as a surface-enhanced Raman scattering probe to demonstrate the potential effects of the synthesized arrays. This hydrophobic platform enables the concentration and delivery of analyte molecules into the surface enhanced Raman spectroscopy sensitive site while suppressing the coffee ring effect generated by the smooth contraction motion of the base contact radius of the droplet without any pinning. Thus, the limit of detection (LOD) of the R6G analyte was lowered to 10−10 M and the homogenous dispersion of surface enhanced Raman spectroscopy hotspots within the self-assembly reproducible surface enhanced Raman spectroscopy signal. This new method enables a broad range of packing patterns and mechanisms by changing the host nanoparticles in the dispersion.
Nitrogen addition alters soil fungal communities, but root fungal communities are resistant to change
Authors: Carrell Alyssa A. , Hicks Brittany B. , Sidelinger Emilie , Johnston Eric R. , Jawdy Sara S. , Clark Miranda M. , Klingeman Dawn M. , Cregger Melissa A.
Published: January 2023

Plants are colonized by numerous microorganisms serving important symbiotic functions that are vital to plant growth and success. Understanding and harnessing these interactions will be useful in both managed and natural ecosystems faced with global change, but it is still unclear how variation in environmental conditions and soils influence the trajectory of these interactions. In this study, we examine how nitrogen addition alters plant-fungal interactions within two species ofPopulus-Populus deltoidesandP.trichocarpa. In this experiment, we manipulated plant host, starting soil (native vs. away for each tree species), and nitrogen addition in a fully factorial replicated design. After ~10 weeks of growth, we destructively harvested the plants and characterized plant growth factors and the soil and root endosphere fungal communities using targeted amplicon sequencing of the ITS2 gene region. Overall, we found nitrogen addition altered plant growth factors, e.g., plant height, chlorophyll density, and plant N content. Interestingly, nitrogen addition resulted in a lower fungal alpha diversity in soils but not plant roots. Further, there was an interactive effect of tree species, soil origin, and nitrogen addition on soil fungal community composition. Starting soils collected from Oregon and West Virginia were dominated by the ectomycorrhizal fungiInocybe(55.8% relative abundance), but interestingly whenP.deltoideswas grown in its native West Virginia soil, the roots selected for a high abundance of the arbuscular mycorrhizal fungi,Rhizophagus. These results highlight the importance of soil origin and plant species on establishing plant-fungal interactions.
Non-antibiotic prevention and treatment against Acinetobacter baumannii infection: Are vaccines and adjuvants effective strategies?
Authors: Hu Yue , Zhang Xianqin , Deng Shanshan , Yue Changwu , Jia Xu , Lyu Yuhong
Published: January 2023

Acinetobacter baumannii (A. baumannii) is a Gram-negative opportunistic pathogen widely attached to the surface of medical instruments, making it one of the most common pathogens of nosocomial infection, and often leading to cross-infection and co-infection. Due to the extensive antibiotic and pan-resistance, A. baumannii infection is facing fewer treatment options in the clinic. Therefore, the prevention and treatment of A. baumannii infection have become a tricky global problem. The requirement for research and development of the new strategy is urgent. Now, non-antibiotic treatment strategies are urgently needed. This review describes the research on A. baumannii vaccines and antibacterial adjuvants, discusses the advantages and disadvantages of different candidate vaccines tested in vitro and in vivo, especially subunit protein vaccines, and shows the antibacterial efficacy of adjuvant drugs in monotherapy.
CRISPR-Cas13 in malaria parasite: Diagnosis and prospective gene function identification
Authors: Quansah Elvis , Chen Yihuan , Yang Shijie , Wang Junyan , Sun Danhong , Zhao Yangxi , Chen Ming , Yu Li , Zhang Chao
Published: January 2023

Malaria caused by Plasmodium is still a serious public health problem. Genomic editing is essential to understand parasite biology, elucidate mechanical pathways, uncover gene functions, identify novel therapeutic targets, and develop clinical diagnostic tools. Recent advances have seen the development of genomic diagnostic technologies and the emergence of genetic manipulation toolbox comprising a host of several systems for editing the genome of Plasmodium at the DNA, RNA, and protein level. Genomic manipulation at the RNA level is critical as it allows for the functional characterization of several transcripts. Of notice, some developed artificial RNA genome editing tools hinge on the endogenous RNA interference system of Plasmodium. However, Plasmodium lacks a robust RNAi machinery, hampering the progress of these editing tools. CRISPR-Cas13, which belongs to the VI type of the CRISPR system, can specifically bind and cut RNA under the guidance of crRNA, with no or minimal permanent genetic scar on genes. This review summarizes CRISPR-Cas13 system from its discovery, classification, principle of action, and diagnostic platforms. Further, it discusses the application prospects of Cas13-based systems in Plasmodium and highlights its advantages and drawbacks.
Communication of gut microbiota and brain via immune and neuroendocrine signaling
Authors: Kasarello Kaja , Cudnoch-Jedrzejewska Agnieszka , Czarzasta Katarzyna
Published: January 2023

The gastrointestinal tract of the human is inhabited by about 5 × 1013 bacteria (of about 1,000 species) as well as archaea, fungi, and viruses. Gut microbiota is known to influence the host organism, but the host may also affect the functioning of the microbiota. This bidirectional cooperation occurs in three main inter-organ signaling: immune, neural, and endocrine. Immune communication relies mostly on the cytokines released by the immune cells into circulation. Also, pathogen-associated or damage-associated molecular patterns (PAMPs or DAMPs) may enter circulation and affect the functioning of the internal organs and gut microbiota. Neural communication relies mostly on the direct anatomical connections made by the vagus nerve, or indirect connections via the enteric nervous system. The third pathway, endocrine communication, is the broadest one and includes the hypothalamic-pituitary-adrenal axis. This review focuses on presenting the latest data on the role of the gut microbiota in inter-organ communication with particular emphasis on the role of neurotransmitters (catecholamines, serotonin, gamma-aminobutyric acid), intestinal peptides (cholecystokinin, peptide YY, and glucagon-like peptide 1), and bacterial metabolites (short-chain fatty acids).
Comparison between two self-guided tinnitus pitch matching methods
Authors: Santacruz Jose L. , de Kleine Emile , van Dijk Pim
Published: January 2023

Introduction

Tinnitus pitch matching is a procedure by which the frequency of an external sound is manipulated in such a way that its pitch matches the one of the tinnitus. The correct measure of the tinnitus pitch plays an important role in the effectiveness of any sound-based therapies. To date, this assessment is difficult due to the subjective nature of tinnitus. Some of the existing pitch matching methods present a challenge for both patients and clinicians, and require multiple adjustments of frequency and loudness, which becomes increasingly difficult in case of coexisting hearing loss. In this paper, we present the comparison in terms of reliability between two self-guided pitch matching methods: the method of adjustment (MOA) and the multiple-choice method (MCM).

Methods

20 participants with chronic tinnitus and hearing loss underwent the two assessments in two different sessions, 1 week apart. Measures of intraclass correlation (ICC) and difference in octaves (OD) within-method and within-session were obtained.

Results

Both methods presented good reliability, and the obtained values of ICC and OD suggested that both methods might measure a different aspect of tinnitus.

Discussion

Our results suggest that a multiple-choice method (MCM) for tinnitus pitch matching is as reliable in a clinical population as more conventional methods.
Axonal connections between S1 barrel, M1, and S2 cortex in the newborn mouse
Authors: Gellért Levente , Luhmann Heiko J. , Kilb Werner
Published: January 2023

The development of functionally interconnected networks between primary (S1), secondary somatosensory (S2), and motor (M1) cortical areas requires coherent neuronal activity via corticocortical projections. However, the anatomical substrate of functional connections between S1 and M1 or S2 during early development remains elusive. In the present study, we used ex vivo carbocyanine dye (DiI) tracing in paraformaldehyde-fixed newborn mouse brain to investigate axonal projections of neurons in different layers of S1 barrel field (S1Bf), M1, and S2 toward the subplate (SP), a hub layer for sensory information transfer in the immature cortex. In addition, we performed extracellular recordings in neocortical slices to unravel the functional connectivity between these areas. Our experiments demonstrate that already at P0 neurons from the cortical plate (CP), layer 5/6 (L5/6), and the SP of both M1 and S2 send projections through the SP of S1Bf. Reciprocally, neurons from CP to SP of S1Bf send projections through the SP of M1 and S2. Electrophysiological recordings with multi-electrode arrays in cortical slices revealed weak, but functional synaptic connections between SP and L5/6 within and between S1 and M1. An even lower functional connectivity was observed between S1 and S2. In summary, our findings demonstrate that functional connections between SP and upper cortical layers are not confined to the same cortical area, but corticocortical connection between adjacent cortical areas exist already at the day of birth. Hereby, SP can integrate early cortical activity of M1, S1, and S2 and shape the development of sensorimotor integration at an early stage.
Calf muscle pump tensing as a novel maneuver to improve the diagnostic performance of detecting patent foramen ovale during transesophageal echocardiography
Authors: Zhu Jianbo , Chen Anni , Zhu Lei , Li Yun , Tang Yunyi , Huang Yanhua , Shen Hualiang , Jiang Zhenzhen , Liu Xiatian
Published: January 2023

Objective

The Valsalva maneuver is the most sensitive provocative maneuver for patent foramen ovale detection. However, nearly half of patients are unable to perform the Valsalva maneuver well. The aim of this study was to investigate the mechanism of action of calf muscle pump tensing (TENSE) as a novel patent foramen ovale (PFO) provocative maneuver and to evaluate the diagnostic value for PFO and the effect on right-to-left shunt volume compared with the Valsalva maneuver.

Methods

This study prospectively investigated 171 patients who were highly suspected to have PFO clinically. Five patients with atrial septal defects newly diagnosed on transesophageal echocardiography (TEE) were excluded. 166 patients were injected with agitated saline under three provocative maneuvers: Valsalva maneuver, TENSE, and Valsalva + TENSE combined maneuver. The patients were divided into the effective Valsalva group (n = 93) and ineffective Valsalva group (n = 73) according to whether they could perform an effective Valsalva maneuver. TENSE consisted of the straightening of both lower limbs, and when the right atrium was filled with microbubbles, the patient performed instantaneous ankle dorsiflexion movements while maintaining dorsiflexion for 3–5 s.

Results

Overall, the PFO detection rate of the Valsalva + TENSE combined maneuver (78 [50.1%]) was significantly higher than that of the Valsalva maneuver (51 [30.7%]) and TENSE maneuver (57 [34.3%]) (P < 0.001). In the patients who were able to perform an effective Valsalva maneuver, the PFO detection rate by TENSE was not significantly different from that by the Valsalva maneuver (Valsalva 37/93 [39.8%] vs. TENSE 31/93 [33.3%], P > 0.05), while for the patients who performed an ineffective Valsalva maneuver, the PFO detection rate by the TENSE maneuver was higher than that by the Valsalva maneuver (TENSE 26/73 [35.6%] vs. Valsalva14/73[19.2%], P = 0.017).

Conclusion

TENSE is a simple and effective provocative maneuver in the diagnosis of PFO using TEE and can assist the Valsalva maneuver. For patients who cannot perform an effective Valsalva maneuver, TENSE can be an alternative to the Valsalva maneuver to some extent.
A systematic review with meta-analysis: Traditional Chinese tuina therapy for insomnia
Authors: Wang Zheng , Xu Hui , Zhou Hang , Lei Yang , Yang Lulu , Guo Juan , Wang Yuxia , Zhou Yunfeng
Published: January 2023

Background

With changes in the way of life and work, an increasing number of people are suffering from insomnia. In China, a traditional Chinese medicine method tuina is widely used for the treatment of insomnia. However, the evidence for tuina therapy for insomnia remains controversial. Therefore, this systematic review aimed to evaluate the effect of tuina therapy on the symptoms of patients with primary insomnia.

Methods

From establishment to January 2022, a comprehensive literature search was conducted using seven electronic databases to identify randomized controlled trials of tuina therapy for insomnia. We used RevMan 5.4 software and the GRADEpro Guideline Development Tool to evaluate the quality of the included randomized controlled trials and perform the meta-analysis. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool. Subgroup analysis was performed according to the different intervention methods. The I2 statistic was used to assess the heterogeneity.

Results

Eighteen studies conducted from 2011 to 2021 were included, with a total of 1,471 patients. In terms of efficacy, tuina alone was superior to other treatments [odds ratio (OR), 3.46; 95% confidence interval (CI), 2.15, 5.55; P < 0.00001]; tuina combined with other treatments (acupuncture, scraping, auricular acupuncture, Suanzaoren decoction, estazolam) was more effective than other single therapies (OR, 3.99; 95% CI, 2.84, 5.61; P < 0.00001). In terms of Pittsburgh Sleep Quality Scale score, the improvement in insomnia patients by tuina alone was better than that of other treatments [standardized mean difference (SMD), −2.57; 95% CI, −2.98, −2.17; P < 0.00001], and tuina combined with other treatments (acupuncture, scraping, auricular point pressing, Suanzaoren decoction, estazolam) was better than other single therapies (SMD, −2.83; 95% CI, −2.98, −2.68; P < 0.00001).

Conclusion

This meta-analysis revealed that tuina can significantly improve the clinical efficacy and sleep quality of patients with primary insomnia. This study provides a theoretical basis and treatment guidance for patients with primary insomnia.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022355742.
Sensory and motor cortical excitability changes induced by rTMS and sensory stimulation in stroke: A randomized clinical trial
Authors: de Freitas Zanona Aristela , Romeiro da Silva Andressa Claudia , Baltar do Rego Maciel Adriana , Shirahige Gomes do Nascimento Livia , Bezerra da Silva Amanda , Piscitelli Daniele , Monte-Silva Katia
Published: January 2023

Background

The ability to produce coordinated movement is dependent on dynamic interactions through transcallosal fibers between the two cerebral hemispheres of the brain. Although typically unilateral, stroke induces changes in functional and effective connectivity across hemispheres, which are related to sensorimotor impairment and stroke recovery. Previous studies have focused almost exclusively on interhemispheric interactions in the primary motor cortex (M1).

Objective

To identify the presence of interhemispheric asymmetry (ASY) of somatosensory cortex (S1) excitability and to investigate whether S1 repetitive transcranial magnetic stimulation (rTMS) combined with sensory stimulation (SS) changes excitability in S1 and M1, as well as S1 ASY, in individuals with subacute stroke.

Methods

A randomized clinical trial. Participants with a single episode of stroke, in the subacute phase, between 35 and 75 years old, were allocated, randomly and equally balanced, to four groups: rTMS/sham SS, sham rTMS/SS, rTMS/SS, and sham rTMS/Sham SS. Participants underwent 10 sessions of S1 rTMS of the lesioned hemisphere (10 Hz, 1,500 pulses) followed by SS. SS was applied to the paretic upper limb (UL) (active SS) or non-paretic UL (sham SS). TMS-induced motor evoked potentials (MEPs) of the paretic UL and somatosensory evoked potential (SSEP) of both ULs assessed M1 and S1 cortical excitability, respectively. The S1 ASY index was measured before and after intervention. Evaluator, participants and the statistician were blinded.

Results

Thirty-six participants divided equally into groups (nine participants per group). Seven patients were excluded from MEP analysis because of failure to produce consistent MEP. One participant was excluded in the SSEP analysis because no SSEP was detected. All somatosensory stimulation groups had decreased S1 ASY except for the sham rTMS/Sham SS group. When compared with baseline, M1 excitability increased only in the rTMS/SS group.

Conclusion

S1 rTMS and SS alone or in combination changed S1 excitability and decreased ASY, but it was only their combination that increased M1 excitability.

Clinical trial registration

clinicaltrials.gov, identifier (NCT03329807).
Dietary patterns and indicators of cardiometabolic risk among rural adolescents: A cross-sectional study at 15-year follow-up of the MINIMat cohort
Authors: Islam Mohammad Redwanul , Rahman Syed Moshfiqur , Selling Katarina , Näsänen-Gilmore Pieta , Kippler Maria , Kajantie Eero , Rahman Anisur , Pervin Jesmin , Ekström Eva-Charlotte
Published: January 2023

Background

Diet being a modifiable factor, its relationship with cardiometabolic risk is of public health interest. The vast majority of studies on associations of dietary patterns with cardiometabolic risk indicators among adolescents are from high-income countries and urban settings. We sought to describe dietary patterns and examine their associations with selected cardiometabolic risk indicators–waist circumference (WC), systolic blood pressure, fasting lipid profile and insulin resistance–along with its gender stratification among adolescents in a low-income, rural setting.

Methods

This cross-sectional study utilized data from the 15-year follow-up of the Maternal and Infant Nutrition Interventions in Matlab (MINIMat) cohort in southeast Bangladesh. The children who were born as singletons to the mothers randomized in the MINIMat trial and had valid birth anthropometrics were eligible for the follow-up. We employed a single, qualitative 24-hour recall to assess diet. Dietary patterns were derived from simple K-means cluster analysis, and calculation of dietary diversity score (DDS) using a validated instrument. Anthropometric parameters and systolic blood pressure were recorded. Fasting plasma triglyceride, total cholesterol, low- and high-density lipoproteins, insulin and glucose levels were measured. We calculated insulin resistance using the Homeostasis Model Assessment equation (HOMA-IR). Three right-skewed outcome variables were natural log (Ln) transformed: WC, triglyceride and HOMA-IR. Omnibus and gender-specific multiple linear regression models were fitted.

Results

Among 2,253 adolescents (52.1% girls, 7.1% overweight/obese), we identified four diet clusters: Traditional, Fish-dominant, Meat-dominant, and High-variety. No significant associations were found between the clusters and indicators. On gender-stratification, triglyceride levels were lower among boys in the Fish-dominant (Ln-triglyceride βadjusted: −0.09; 95% confidence interval (CI): −0.15, −0.02) and Meat-dominant (Ln-triglyceride βadjusted: −0.08; 95% CI: −0.15, −0.004) clusters than among boys in the Traditional cluster. Compared to boys in the bottom quartile of DDS, boys in the top quartile had 2.1 mm of Hg (95% CI: 0.5, 3.6) higher systolic blood pressure and 1.9% (95% CI: 0.01–3.8%) higher WC.

Conclusion

While statistically significant, the gender-specific differences in triglyceride, systolic blood pressure, and waist circumference across dietary patterns were small. Associations between dietary patterns and cardiometabolic risk indicators may require a time lag beyond mid-adolescence to manifest in a rural setting. Prospective studies are warranted to delineate the magnitude and direction of those associations.
Comprehensive studies of biological characteristics, phytochemical profiling, and antioxidant activities of two local citrus varieties in China
Authors: Sun Lifang , Xu Jianguo , Nasrullah  , Wang Luoyun , Nie Zhenpeng , Huang Xiu , Sun Jianhua , Ke Fuzhi
Published: January 2023

Citrus is widely grown all over the world, and citrus fruits have long been recognized for their nutritional and medical value for human health. However, some local citrus varieties with potentially important value are still elusive. In the current study, we elucidated the biological characteristics, phylogenetic and phytochemical profiling, antioxidants and antioxidant activities of the two local citrus varieties, namely Zangju and Tuju. The physiological and phylogenetic analysis showed that Zangju fruit has the characteristics of wrinkled skin, higher acidity, and phylogenetically closest to sour mandarin Citrus sunki, whereas, Tuju is a kind of red orange with vermilion peel, small fruit and high sugar content, and closely clustered with Citrus erythrosa. The phytochemical analysis showed that many nutrition and antioxidant related differentially accumulated metabolites (DAMs) were detected in the peel and pulp of Zangju and Tuju fruits. Furthermore, it was found that the relative abundance of some key flavonoids and phenolic acids, such as tangeritin, sinensetin, diosmetin, nobiletin, and sinapic acid in the peel and pulp of Zangju and Tuju were higher than that in sour range Daidai and satsuma mandarin. Additionally, Zangju pulp and Tuju peel showed the strongest ferric reducing/antioxidant power (FRAP) activity, whereas, Tuju peel and pulp showed the strongest DPPH and ABTS free radical scavenging activities, respectively. Moreover, both the antioxidant activities of peel and pulp were significantly correlated with the contents of total phenols, total flavonoids or ascorbic acid. These results indicate that the two local citrus varieties have certain nutritional and medicinal value and potential beneficial effects on human health. Our findings will also provide an important theoretical basis for further conservation, development and medicinal utilization of Zangju and Tuju.
Progress and perspectives of perioperative immunotherapy in non-small cell lung cancer
Authors: Peng Yurong , Li Zhuo , Fu Yucheng , Pan Yue , Zeng Yue , Liu Junqi , Xiao Chaoyue , Zhang Yingzhe , Su Yahui , Li Guoqing , Wu Fang
Published: January 2023

Lung cancer is one of the leading causes of cancer-related death. Lung cancer mortality has decreased over the past decade, which is partly attributed to improved treatments. Curative surgery for patients with early-stage lung cancer is the standard of care, but not all surgical treatments have a good prognosis. Adjuvant and neoadjuvant chemotherapy are used to improve the prognosis of patients with resectable lung cancer. Immunotherapy, an epoch-defining treatment, has improved curative effects, prognosis, and tolerability compared with traditional and ordinary cytotoxic chemotherapy, providing new hope for patients with non-small cell lung cancer (NSCLC). Immunotherapy-related clinical trials have reported encouraging clinical outcomes in their exploration of different types of perioperative immunotherapy, from neoadjuvant immune checkpoint inhibitor (ICI) monotherapy, neoadjuvant immune-combination therapy (chemoimmunotherapy, immunotherapy plus antiangiogenic therapy, immunotherapy plus radiotherapy, or concurrent chemoradiotherapy), adjuvant immunotherapy, and neoadjuvant combined adjuvant immunotherapy. Phase 3 studies such as IMpower 010 and CheckMate 816 reported survival benefits of perioperative immunotherapy for operable patients. This review summarizes up-to-date clinical studies and analyzes the efficiency and feasibility of different neoadjuvant therapies and biomarkers to identify optimal types of perioperative immunotherapy for NSCLC.
Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival
Authors: Singh Lakhveer , Nair Lakshmi , Kumar Dinesh , Arora Mandeep Kumar , Bajaj Sakshi , Gadewar Manoj , Mishra Shashank Shekher , Rath Santosh Kumar , Dubey Amit Kumar , Kaithwas Gaurav , Choudhary Manjusha , Singh Manjari
Published: January 2023

It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME.
Case Report: A case of synchronous right upper lobe adenocarcinoma and left lower lobe squamous cell carcinoma treated with immune checkpoint inhibitor plus chemotherapy
Authors: Liu Yujiao , Yu Han , Dong Youhong , Zhang Dongdong
Published: January 2023

Globally, lung cancer is the leading cause of cancer-related mortality. Multiple primary lung cancers (MPLC) account for a very small portion of all primary lung cancer cases. Importantly, a quick and precise differentiation between MPLC and intrapulmonary metastases is directly related to patient prognoses as treatment strategies vary according to pathological type. Synchronous MPLC are most commonly seen in the same lung. Here, we report a rare case of a patient with synchronous MPLC of both lungs. A 67-year-old man, with a 1-month cough and expectoration history, was admitted in our hospital. Computed tomography (CT) chest scan revealed a lower lobe nodule in the left lung and an upper lobe nodule in the right lung. He underwent successive fiberoptic bronchoscopy and CT-guided percutaneous pulmonary aspiration biopsy of both lungs. The pathological diagnosis was squamous cell carcinoma of the left lung and adenocarcinoma of the right lung.
Case Report: CTC1 mutations in a patient with diffuse hepatic and splenic hemangiomatosis complicated by Kasabach–Merritt syndrome
Authors: He Xin , Guo Zi-Wen , Niu Xiao-Min
Published: January 2023

Diffuse hemangiomatosis of the liver and spleen is rare. Currently, few studies are available on diffuse hepatic and splenic hemangiomatosis accompanied by Kasabach–Merritt syndrome (KMS). The conserved telomere maintenance component 1 (CTC1) gene contributes to telomere maintenance and replication by forming the telomeric capping complex. Herein, we report a case of diffuse hemangiomatosis in the liver and spleen accompanied by KMS in a 59-year-old woman who carried two novel heterozygous CTC1 variants: c.435+9A>C and c.3074C>T (p.Ala1025Val). Using next-generation sequencing, we detected mutations in the CTC1 gene in our patient, who had chief complaints of fatigue and abdominal distension complicated by severe thrombocytopenia and consumptive coagulopathy. Clinical symptoms, laboratory tests, and imaging findings led to the diagnosis of diffuse hepatic and splenic hemangiomatosis accompanied by KMS. The patient was treated with prednisone, thalidomide, and sirolimus, and her general condition was ameliorated at the 4-month follow-up with improved platelet count and coagulation function. A CTC1 gene mutation may be involved in the pathological process of vascular diseases. A combination treatment regimen of prednisone, thalidomide, and sirolimus may be effective for KMS.
Drug repositioning via host-pathogen protein-protein interactions for the treatment of cervical cancer
Authors: Kori Medi , Turanli Beste , Arga Kazim Yalcin
Published: January 2023

Introduction

Integrating interaction data with biological knowledge can be a critical approach for drug development or drug repurposing. In this context, host-pathogen-protein-protein interaction (HP-PPI) networks are useful instrument to uncover the phenomena underlying therapeutic effects in infectious diseases, including cervical cancer, which is almost exclusively due to human papillomavirus (HPV) infections. Cervical cancer is one of the second leading causes of death, and HPV16 and HPV18 are the most common subtypes worldwide. Given the limitations of traditionally used virus-directed drug therapies for infectious diseases and, at the same time, recent cancer statistics for cervical cancer cases, the need for innovative treatments becomes clear.

Methods

Accordingly, in this study, we emphasize the potential of host proteins as drug targets and identify promising host protein candidates for cervical cancer by considering potential differences between HPV subtypes (i.e., HPV16 and HPV18) within a novel bioinformatics framework that we have developed. Subsequently, subtype-specific HP-PPI networks were constructed to obtain host proteins. Using this framework, we next selected biologically significant host proteins. Using these prominent host proteins, we performed drug repurposing analysis. Finally, by following our framework we identify the most promising host-oriented drug candidates for cervical cancer.

Results

As a result of this framework, we discovered both previously associated and novel drug candidates, including interferon alfacon-1, pimecrolimus, and hyaluronan specifically for HPV16 and HPV18 subtypes, respectively.

Discussion

Consequently, with this study, we have provided valuable data for further experimental and clinical efforts and presented a novel bioinformatics framework that can be applied to any infectious disease.
The mesenchymal compartment in myelodysplastic syndrome: Its role in the pathogenesis of the disorder and its therapeutic targeting
Authors: Pontikoglou Charalampos G. , Matheakakis Angelos , Papadaki Helen A.
Published: January 2023

Myelodysplastic syndromes include a broad spectrum of malignant myeloid disorders that are characterized by dysplastic ineffective hematopoiesis, reduced peripheral blood cells counts and a high risk of progression to acute myeloid leukemia. The disease arises primarily because of accumulating chromosomal, genetic and epigenetic changes as well as immune-mediated alterations of the hematopoietic stem cells (HSCs). However, mounting evidence suggests that aberrations within the bone marrow microenvironment critically contribute to myelodysplastic syndrome (MDS) initiation and evolution by providing permissive cues that enable the abnormal HSCs to grow and eventually establish and propagate the disease. Mesenchymal stromal cells (MSCs) are crucial elements of the bone marrow microenvironment that play a key role in the regulation of HSCs by providing appropriate signals via soluble factors and cell contact interactions. Given their hematopoiesis supporting capacity, it has been reasonable to investigate MSCs’ potential involvement in MDS. This review discusses this issue by summarizing existing findings obtained by in vitro studies and murine disease models of MDS. Furthermore, the theoretical background of targeting the BM-MSCs in MDS is outlined and available therapeutic modalities are described.
Emerging functions of C/EBPβ in breast cancer
Authors: Matherne Megan G. , Phillips Emily S. , Embrey Samuel J. , Burke Caitlin M. , Machado Heather L.
Published: January 2023

Breast tumorigenesis relies on complex interactions between tumor cells and their surrounding microenvironment, orchestrated by tightly regulated transcriptional networks. C/EBPβ is a key transcription factor that regulates the proliferation and differentiation of multiple cell types and modulates a variety of biological processes such as tissue homeostasis and the immune response. In addition, C/EBPβ has well-established roles in mammary gland development, is overexpressed in breast cancer, and has tumor-promoting functions. In this review, we discuss context-specific roles of C/EBPβ during breast tumorigenesis, isoform-specific gene regulation, and regulation of the tumor immune response. We present challenges in C/EBPβ biology and discuss the importance of C/EBPβ isoform-specific gene regulation in devising new therapeutic strategies.
Short-term effects of intravitreal anti-vascular endothelial growth factor agents on body weight and multiple systems after treatment for retinopathy of prematurity
Authors: Chen Jing , Hao Qingfei , Zhang Jing , Du Yanna , Chen Haoming , Cheng Xiuyong
Published: January 2023

Objectives

This study's goal was to assess the short-term effect on body weight and multiple systems following intravitreal injections of ranibizumab and aflibercept for retinopathy of prematurity (ROP).

Methods

We retrospectively assessed infants with ROP who received intravitreal anti-vascular endothelial growth factor agents (VEGF) treatment at our hospital. They were classified into 2 groups based on the drugs administered: the intravitreal ranibizumab (IVR) group and the intravitreal aflibercept (IVA) group. The body weight (BW) gains for the pre-treatment week, the 1st week after treatment, and the 2nd week after treatment were compared for each group. Additionally, other parameters such as blood pressure, heart rate, oxygen concentration, volume of milk and output of urine at four time points were also measured. We used repeated measurement analysis of variance analyzed these data.

Results

In total, 95 preterm infants were recruited, including 51 cases in the IVR group and 44 cases in the IVA group. The BW gain for the 1st week after treatment was significantly lower than the pre-treatment week in each group (P < 0.05), while there was no decrease in weekly BW gain in the 2nd week after treatment compared with that pre-treatment week. Based on the comparison between groups, the BW gain in the IVR group was significantly higher than in the IVA group in the second post-treatment week. Repeated measurement analysis of variance showed that there were no significant differences in blood pressure, heart rate, oxygen concentration, volume of milk and output of urine in both groups over time.

Conclusions

IVR and IVA could have a short-term inhibitive effect on body weight gain in infants after treatment for ROP, whereas there is no significant impact on other systems.
Atypical maternal interaction is associated with elevated levels of hair cortisol in children
Authors: Köhler-Dauner Franziska , Mayer Inka , Hitzler Melissa , Karabatsiakis Alexander , Matits Lynn , Bach Alexandra M. , Rost Katharina , Fegert Jörg M. , Kolassa Iris-Tatjana , Ziegenhain Ute
Published: January 2023

The quality of maternal caregiving is an important factor in the healthy development of a child. One consequence of prolonged insensitive and atypical maternal interaction behavior (e.g., withdrawing from interactions with the child and role-reversal, i.e., the takeover of the parental role or parts of it by the child) in mother-child-dyads can cause alteration of the child's stress response system. Higher salivary cortisol concentrations were reported in infants and toddlers directly after negative interactions with their parents. However, no study to date has examined the association between atypical maternal interaction behavior and hair cortisol concentrations (HCC) in infants. Here, we studied the association of maternal interaction behavior with HCC of the child. Mother-child dyads (N = 112) participated in the longitudinal study My Childhood—Your Childhood. The AMBIANCE scale and its subscales were used to assess atypical maternal interaction behavior during the Strange Situation Procedure. Chronic stress levels in the child were assessed by HCC of 3 cm hair strands at the age of 12 months. Maternal educational level (operationalized in highest education level) served as a control variable. Robust multiple linear regression analyses revealed that role/boundary confusion was associated with HCC, i.e., the higher atypical interaction behavior of the mother the higher the HCC in the children. By measuring hair cortisol in this study, it is possible to determine the average long-term activity of the child's stress response system.Thus, atypical maternal interaction behavior could be a risk factor for persistent stress in children, contributing to a higher risk for negative health outcomes in later life. The results of this study highlight the importance of early intervention programs that focus on the relationship between mother and child.
A North American, single-center experience implanting fenestrated atrial devices and atrial flow regulators into a heterogeneous group of pediatric pulmonary hypertension patients
Authors: Youssef David Edward , Averin Konstantin , Richards Susan , Sheppard Catherine , Seaman Cameron , Pietrosanu Matthew , Bates Angela
Published: January 2023

Introduction

The clinical deterioration commonly experienced by pediatric patients with pulmonary arterial hypertension (PAH) has motivated a shift in the treatment of pulmonary hypertension (PH) through innovations in surgical salvage interventions. The Occlutech fenestrated atrial septal defect (FASD) Occluder and the atrial flow regulator (AFR), which provides a protective, atrial-level shunt during hypertensive crises, have found an important role in treating pediatric patients with PAH. Other groups of pediatric patients with PH may also benefit from a similar protective physiology. The primary aim of this work is to present a single center's experience with AFR and FASD devices for managing a heterogeneous group of pediatric PH patients. A secondary goal is to identify hemodynamic changes and complications following device implantation.

Materials and Methods

We performed a retrospective review of all pediatric PH patients who, after being found suitable, either successfully or unsuccessfully received an FASD or AFR device between January 2015 and December 2021 at the Stollery Children's Hospital in Edmonton, Canada.

Results

Fourteen patients (eight female) with a median age of 4.6 (range 0.3–17.9) years and a median body mass index of 15.1 (Q1 = 13.8, Q3 = 16.8) kg/m2 underwent device implantation: five received FASDs, eight received AFRs, and one was ultimately unable to receive an implant due to thrombosed iliac vessels and required surgical intervention. Of the fourteen patients, seven were in group 1 (PAH), one was in group 3 (lung disease), and six were in group 5 (primarily pulmonary hypertension vascular disease) under the World Symposium PH classification. All patients were on mono-, dual-, or triple-drug PH therapy. Device stabilization was not possible for two patients, who then required a repeat catheterization. Of the group 1 patients, three AFR and three FASD implants were successful, while one FASD implant was unsuccessful due to thrombosed vessels. At a six-month clinical assessment, all group 1 patients had patent devices and improved WHO FCs.

Conclusion

This work presents a single center's experience with AFR and FASD implants in a heterogeneous group of fourteen pediatric patients with severe PH. This treatment strategy is novel in the pediatric population and so this work provides momentum for future studies of interventional cardiac catheterization procedures for pediatric patients with PH. Further collaborations are required to develop criteria to identify ideal pediatric candidates and optimally time interventions in order to maximize the benefits of this treatment.
Efficacy of kangaroo mother care combined with neonatal phototherapy in newborns with non-pathological jaundice: A meta-analysis
Authors: Huang Xiang , Chen Meiling , Fu Rongrong , He Wei , He Yujing , Shentu Haojie , Zhu Suping
Published: January 2023

Background

The kangaroo-mother care method (KMC) is a skin-to-skin contact-centered care approach with numerous benefits for neonates, but its impact on the treatment of jaundiced neonates is unknown. This study aimed to investigate the efficacy of KMC combined with neonatal phototherapy (NNPT) in treating neonates with non-pathological jaundice.

Methods

Relevant articles were searched in PubMed, Embase, Web of Science, and Cochrane Library databases from database establishment to April 2022. The outcomes included, without limitation, serum bilirubin levels, and duration of phototherapy.

Results

This meta-analysis included five studies (4 randomized controlled trials and 1 observational study) involving four hundred eighty-two neonates with non-pathological jaundice. The results showed that the group receiving KMC combined with NNPT had lower serum bilirubin at 72 h after intervention [weighted mean difference (WMD) = −1.51, p = 0.03], shorter duration of phototherapy [standard mean difference (SMD) = −1.45, p < 0.001] and shorter duration of hospitalization (SMD = −1.32, p = 0.002) compared to NNPT group. There was no difference in peak bilirubin in both groups of neonates (WMD = −0.12, p = 0.62).

Conclusions

KMC combined with NNPT helped to treat non-pathological jaundice in newborns compared to NNPT alone.
Development and optimization of nanoparticles loaded with erucin, a dietary isothiocyanate isolated from Eruca sativa: Antioxidant and antiproliferative activities in ehrlich-ascites carcinoma cell line
Authors: Singh Sharabjit , Singh Gurdeep , Attri Shivani , Kaur Prabhjot , Rashid Farhana , Bedi Neena , Haque Shafiul , Janahi Essam M. , Arora Saroj
Published: January 2023

The study on Erucin (ER) has gained interest of nutraceutical and pharmaceutical industries because of its anti-cancer properties. Erucin is an isothiocyanate obtained from the seeds of Eruca sativa which possess certain drawbacks such as poor aqueous solubility and bioavailability. Therefore, the present study aimed at developing ER-cubosomes (CUB) by solvent evaporation technique followed by applying Central Composite Design to optimize ER loaded cubosomes. For this purpose, independent variables selected were Monoolein (MO) as lipid and Pluronic-84 (P-84) as a stabilizer whereas dependent variables were particle size, percentage of ER loading and percentage of its entrapment efficiency. The cubosomal nanocarriers exhibited particle size in the range of 26 nm, entrapment efficiency of 99.12 ± 0.04% and drug loading of 3.96 ± 0.0001%. Furthermore, to investigate the antioxidant potential, we checked the effect of ER and ER-CUB by DNA nicking assay, DDPH assay and Phosphomolybdate assay, and results showed significant improvement in antioxidant potential for ER-CUB than ER. Similarly, ER-CUB showed enhanced anticancer activity with a marked reduction in IC50 value than ER in MTT assay. These results suggested that ER-CUB produced notable escalation in antioxidant potential and enhanced anticancer activity than ER.