bluuebunny/crossref_metadata_2025 huggingface dataset:
Indoor CO2 monitoring in a surgical intensive care unit under visitation restrictions during the COVID-19 pandemic
Authors: Chou Ying-An , Wang Zheng-Yao , Chang Hsiang-Ching , Liu Yi-Chia , Su Pei-Fang , Huang Yen Ta , Yang Chao-Tung , Lai Chao-Han
Published: July 2023

Background

Indoor CO2 concentration is an important metric of indoor air quality (IAQ). The dynamic temporal pattern of CO2 levels in intensive care units (ICUs), where healthcare providers experience high cognitive load and occupant numbers are frequently changing, has not been comprehensively characterized.

Objective

We attempted to describe the dynamic change in CO2 levels in the ICU using an Internet of Things-based (IoT-based) monitoring system. Specifically, given that the COVID-19 pandemic makes hospital visitation restrictions necessary worldwide, this study aimed to appraise the impact of visitation restrictions on CO2 levels in the ICU.

Methods

Since February 2020, an IoT-based intelligent indoor environment monitoring system has been implemented in a 24-bed university hospital ICU, which is symmetrically divided into areas A and B. One sensor was placed at the workstation of each area for continuous monitoring. The data of CO2 and other pollutants (e.g., PM2.5) measured under standard and restricted visitation policies during the COVID-19 pandemic were retrieved for analysis. Additionally, the CO2 levels were compared between workdays and non-working days and between areas A and B.

Results

The median CO2 level (interquartile range [IQR]) was 616 (524–682) ppm, and only 979 (0.34%) data points obtained in area A during standard visitation were ≥ 1,000 ppm. The CO2 concentrations were significantly lower during restricted visitation (median [IQR]: 576 [556–596] ppm) than during standard visitation (628 [602–663] ppm; p < 0.001). The PM2.5 concentrations were significantly lower during restricted visitation (median [IQR]: 1 [0–1] μg/m3) than during standard visitation (2 [1–3] μg/m3; p < 0.001). The daily CO2 and PM2.5 levels were relatively low at night and elevated as the occupant number increased during clinical handover and visitation. The CO2 concentrations were significantly higher in area A (median [IQR]: 681 [653–712] ppm) than in area B (524 [504–547] ppm; p < 0.001). The CO2 concentrations were significantly lower on non-working days (median [IQR]: 606 [587–671] ppm) than on workdays (583 [573–600] ppm; p < 0.001).

Conclusion

Our study suggests that visitation restrictions during the COVID-19 pandemic may affect CO2 levels in the ICU. Implantation of the IoT-based IAQ sensing network system may facilitate the monitoring of indoor CO2 levels.
Biosynthesized nanoparticles: a novel approach for cancer therapeutics
Authors: Chaturvedi Vivek K. , Sharma Bhaskar , Tripathi Abhay Dev , Yadav Dawesh P. , Singh Kshitij RB , Singh Jay , Singh Ravindra Pratap
Published: July 2023

Nanotechnology has become one of the most rapid, innovative, and adaptable sciences in modern science and cancer therapy. Traditional chemotherapy has limits owing to its non-specific nature and adverse side effects on healthy cells, and it remains a serious worldwide health issue. Because of their capacity to specifically target cancer cells and deliver therapeutic chemicals directly to them, nanoparticles have emerged as a viable strategy for cancer therapies. Nanomaterials disclose novel properties based on size, distribution, and shape. Biosynthesized or biogenic nanoparticles are a novel technique with anti-cancer capabilities, such as triggering apoptosis in cancer cells and slowing tumour growth. They may be configured to deliver medications or other therapies to specific cancer cells or tumour markers. Despite their potential, biosynthesized nanoparticles confront development obstacles such as a lack of standardisation in their synthesis and characterization, the possibility of toxicity, and their efficiency against various forms of cancer. The effectiveness and safety of biosynthesized nanoparticles must be further investigated, as well as the types of cancer they are most successful against. This review discusses the promise of biosynthesized nanoparticles as a novel approach for cancer therapeutics, as well as their mode of action and present barriers to their development.
A clinical analysis of Candida tropicalis bloodstream infections associated with hematological diseases, and antifungal susceptibility: a retrospective survey
Authors: Yang Beibei , Wei Zhenbin , Wu Meiqing , Lai Yongrong , Zhao Weihua
Published: July 2023

Summary objective

To assess the clinical features and outcomes of hematological disease patients with Candida tropicalis bloodstream infections and determine the antifungal susceptibility of C. tropicalis.

Methods

This is a retrospective, single-center, observational study conducted in the Department of Hematology at The First Affiliated Hospital of Guangxi Medical University from January 2013 to December 2021. A total of 26 hematological disease patients with C. tropicalis bloodstream infections were enrolled, and their clinical features, treatment plans, and prognoses were assessed. Univariate analysis was performed by Kaplan–Meier analysis and multivariate analysis was conducted using a Cox regression model. The antifungal susceptibility of C. tropicalis was determined from patient blood cultures.

Results

The patients had a mean age of 35 years (range: 10–65 years), 50% were male (13/26) and 88.5% had hematologic malignancies (23/26) while the remaining three patients included two cases of severe aplastic anemia and one case of β-thalassemia. All patients had neutropenia. Seven patients were initially given azole alone (26.9%), five of whom failed treatment and died (71.4%). Fifteen patients were treated with echinocandin (57.7%), three of whom failed treatment and died (20.0%), and eight patients were treated with amphotericin B (30.8%), two of whom failed treatment and died (25.0%). The total and attributable mortality rates were 42.3 and 34.6%, respectively. Univariate analysis showed that there are six risk factors for attributable deaths among hematological disease patients with C. tropicalis blood infections. These risk factors included septic shock, Pitt bacteremia scores ≥4, procalcitonin levels ≥10 ng/mL, positive plasma (1,3)- β-D glucan assay, serum albumin levels <30.0 g/L, time from fever to antifungal treatment initiation ≥5 days and time between neutropenia and antifungal treatment ≥10 days. Moreover, skin and mucosal infections and a treatment schedule that included amphotericin B and drug combinations are protective factors for attributable deaths. Multivariate analysis showed that septic shock (p = 0.006) was an independent risk factor for attributable death. All isolates were sensitive to flucytosine and amphotericin B. The intermediate or resistance of C. tropicalis to fluconazole, itraconazole and voriconazole were 41.7, 50, and 41.7%, respectively.

Conclusion

Hematological disease patients with C. tropicalis bloodstream infections had a high mortality rate, and early antifungal therapy significantly reduced mortality. Candida tropicalis was highly resistant to azole drugs and sensitive to flucytosine and amphotericin B. According to our study, the preferred agent is amphotericin B and drug combinations should be considered for severe infections.
Silicate solubilizing and plant growth promoting bacteria interact with biogenic silica to impart heat stress tolerance in rice by modulating physiology and gene expression
Authors: Chaganti Chandrakala , Phule Amol Sarjerao , Chandran Latha P. , Sonth Bandeppa , Kavuru Venkat Prasad Babu , Govindannagari Rajani , Sundaram Raman Meenakshi
Published: July 2023

Heat stress caused due to increasing warming climate has become a severe threat to global food production including rice. Silicon plays a major role in improving growth and productivity of rice by aiding in alleviating heat stress in rice. Soil silicon is only sparingly available to the crops can be made available by silicate solubilizing and plant-growth-promoting bacteria that possess the capacity to solubilize insoluble silicates can increase the availability of soluble silicates in the soil. In addition, plant growth promoting bacteria are known to enhance the tolerance to abiotic stresses of plants, by affecting the biochemical and physiological characteristics of plants. The present study is intended to understand the role of beneficial bacteria viz. Rhizobium sp. IIRR N1 a silicate solublizer and Gluconacetobacter diazotrophicus, a plant growth promoting bacteria and their interaction with insoluble silicate sources on morpho-physiological and molecular attributes of rice (Oryza sativa L.) seedlings after exposure to heat stress in a controlled hydroponic system. Joint inoculation of silicates and both the bacteria increased silicon content in rice tissue, root and shoot biomass, significantly increased the antioxidant enzyme activities (viz. superoxidase dismutase, catalase and ascorbate peroxidase) compared to other treatments with sole application of either silicon or bacteria. The physiological traits (viz. chlorophyll content, relative water content) were also found to be significantly enhanced in presence of silicates and both the bacteria after exposure to heat stress conditions. Expression profiling of shoot and root tissues of rice seedlings revealed that seedlings grown in the presence of silicates and both the bacteria exhibited higher expression of heat shock proteins (HSPs viz., OsHsp90, OsHsp100 and 60 kDa chaperonin), hormone-related genes (OsIAA6) and silicon transporters (OsLsi1 and OsLsi2) as compared to seedlings treated with either silicates or with the bacteria alone. The results thus reveal the interactive effect of combined application of silicates along with bacteria Rhizobium sp. IIRR N1, G. diazotrophicus inoculation not only led to augmented silicon uptake by rice seedlings but also influenced the plant biomass and elicited higher expression of HSPs, hormone-related and silicon transporter genes leading to improved tolerance of seedling to heat stress.
The biological relevance of the FspTF transcription factor, homologous of Bqt4, in Fusarium sp. associated with the ambrosia beetle Xylosandrus morigerus
Authors: Carreras-Villaseñor Nohemí , Martínez-Rodríguez Luis A. , Ibarra-Laclette Enrique , Monribot-Villanueva Juan L. , Rodríguez-Haas Benjamín , Guerrero-Analco José A. , Sánchez-Rangel Diana
Published: July 2023

Transcription factors in phytopathogenic fungi are key players due to their gene expression regulation leading to fungal growth and pathogenicity. The KilA-N family encompasses transcription factors unique to fungi, and the Bqt4 subfamily is included in it and is poorly understood in filamentous fungi. In this study, we evaluated the role in growth and pathogenesis of the homologous of Bqt4, FspTF, in Fusarium sp. isolated from the ambrosia beetle Xylosandrus morigerus through the characterization of a CRISPR/Cas9 edited strain in Fsptf. The phenotypic analysis revealed that TF65-6, the edited strain, modified its mycelia growth and conidia production, exhibited affectation in mycelia and culture pigmentation, and in the response to certain stress conditions. In addition, the plant infection process was compromised. Untargeted metabolomic and transcriptomic analysis, clearly showed that FspTF may regulate secondary metabolism, transmembrane transport, virulence, and diverse metabolic pathways such as lipid metabolism, and signal transduction. These data highlight for the first time the biological relevance of an orthologue of Bqt4 in Fusarium sp. associated with an ambrosia beetle.
Myokines as mediators of exercise-induced cognitive changes in older adults: protocol for a comprehensive living systematic review and meta-analysis
Authors: Vints Wouter A. J. , Gökçe Evrim , Langeard Antoine , Pavlova Iuliia , Çevik Özge Selin , Ziaaldini Mohammad Mosaferi , Todri Jasemin , Lena Orges , Sakkas Giorgos K. , Jak Suzanne , Zorba (Zormpa) Ioanna , Karatzaferi Christina , Levin Oron , Masiulis Nerijus , Netz Yael
Published: July 2023

Background

The world’s population is aging, but life expectancy has risen more than healthy life expectancy (HALE). With respect to brain and cognition, the prevalence of neurodegenerative disorders increases with age, affecting health and quality of life, and imposing significant healthcare costs. Although the effects of physical exercise on cognition in advanced age have been widely explored, in-depth fundamental knowledge of the underlying mechanisms of the exercise-induced cognitive improvements is lacking. Recent research suggests that myokines, factors released into the blood circulation by contracting skeletal muscle, may play a role in mediating the beneficial effect of exercise on cognition. Our goal in this ongoing (living) review is to continuously map the rapidly accumulating knowledge on pathways between acute or chronic exercise-induced myokines and cognitive domains enhanced by exercise.

Method

Randomized controlled studies will be systematically collected at baseline and every 6 months for at least 5 years. Literature search will be performed online in PubMed, EMBASE, PsycINFO, Web of Science, SportDiscus, LILACS, IBECS, CINAHL, SCOPUS, ICTRP, and ClinicalTrials.gov. Risk of bias will be assessed using the Revised Cochrane Risk of Bias tool (ROB 2). A random effects meta-analysis with mediation analysis using meta-analytic structural equation modeling (MASEM) will be performed. The primary research question is to what extent exercise-induced myokines serve as mediators of cognitive function. Secondarily, the pooled effect size of specific exercise characteristics (e.g., mode of exercise) or specific older adults’ populations (e.g., cognitively impaired) on the relationship between exercise, myokines, and cognition will be assessed. The review protocol was registered in PROSPERO (CRD42023416996).

Discussion

Understanding the triad relationship between exercise, myokines and cognition will expand the knowledge on multiple integrated network systems communicating between skeletal muscles and other organs such as the brain, thus mediating the beneficial effects of exercise on health and performance. It may also have practical implications, e.g., if a certain myokine is found to be a mediator between exercise and cognition, the optimal exercise characteristics for inducing this myokine can be prescribed. The living review is expected to improve our state of knowledge and refine exercise regimes for enhancing cognitive functioning in diverse older adults’ populations.

Registration

Systematic review and meta-analysis protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on the 24th of April 2023 (registration number CRD42023416996).
Active fault-tolerant anti-input saturation control of a cross-domain robot based on a human decision search algorithm and RBFNN
Authors: Wang Ke , Liu Yong , Huang Chengwei
Published: July 2023

This article presents a cross-domain robot (CDR) that experiences drive efficiency degradation when operating on water surfaces, similar to drive faults. Moreover, the CDR mathematical model has uncertain parameters and non-negligible water resistance. To solve these problems, a radial basis function neural network (RBFNN)-based active fault-tolerant control (AFTC) algorithm is proposed for the robot both on land and water surfaces. The proposed algorithm consists of a fast non-singular terminal sliding mode controller (NTSMC) and an RBFNN. The RBFNN is used to estimate the impact of drive faults, water resistance, and model parameter uncertainty on the robot and the output value compensates the controller. Additionally, an anti-input saturation control algorithm is designed to prevent driver saturation. To optimize the controller parameters, a human decision search algorithm (HDSA) is proposed, which mimics the decision-making process of a crowd. Simulation results demonstrate the effectiveness of the proposed control methods.
Occurrence and severity of myasthenic crisis in an unselected Turkish cohort of patients with myasthenia gravis
Authors: Ozyurt Kose Selen , Nazli Ezgi , Tutkavul Kemal , Gilhus Nils Erik
Published: July 2023

Myasthenia gravis (MG) is a disorder of the neuromuscular junction that can deteriorate into myasthenic crisis, involving weakness of bulbar and respiratory muscles. In this study, we describe the clinical manifestations of myasthenic crisis, identify risk factors, and examine treatments and outcomes. All 95 patients with generalized MG treated at our center during the last 10 years were included in this retrospective study. We collected data from the patients' records, including clinical follow-ups, muscle antibodies, thymic status, and treatments. The characteristics of patients who did and did not experience myasthenic crisis were compared. Features of all myasthenic crises were also assessed. Twelve patients (13%) developed myasthenic crisis during the observation period. Men were more often affected at older ages. Seven patients experienced multiple myasthenic crises. Thymoma increased the risk of a crisis, whereas thymic hyperplasia decreased the risk. Myasthenic crises were more common in the summer months. No patients died during a myasthenic crisis. Risk factors for myasthenic crisis were thymoma, older age, MuSK antibodies, and previous crises. Individualized and active immunosuppressive treatment and optimal intensive care during crises provide a good outcome for patients with generalized MG.
Construction and validation of a nomogram of risk factors for new-onset atrial fibrillation in advanced lung cancer patients after non-surgical therapy
Authors: Chen Jindong , Cao Shuhui , Jin Yu , Rong Wenwen , Wang Hao , Xi Siqi , Gan Tian , He Ben , Zhong Hua , Zhao Liang
Published: July 2023

Objective

Risk factors of new-onset atrial fibrillation (NOAF) in advanced lung cancer patients are not well defined. We aim to construct and validate a nomogram model between NOAF and advanced lung cancer.

Methods

We retrospectively enrolled 19484 patients with Stage III-IV lung cancer undergoing first-line antitumor therapy in Shanghai Chest Hospital between January 2016 and December 2020 (15837 in training set, and 3647 in testing set). Patients with pre-existing AF, valvular heart disease, cardiomyopathy were excluded. Logistic regression analysis and propensity score matching (PSM) were performed to identify predictors of NOAF, and nomogram model was constructed and validated.

Results

A total of 1089 patients were included in this study (807 in the training set, and 282 in the testing set). Multivariate logistic regression analysis showed that age, c-reactive protein, centric pulmonary carcinoma, and pericardial effusion were independent risk factors, the last two of which were important independent risk factors as confirmed by PSM analysis. Nomogram included independent risk factors of age, c-reactive protein, centric pulmonary carcinoma, and pericardial effusion. The AUC was 0.716 (95% CI 0.661–0.770) and further evaluation of this model showed that the C-index was 0.716, while the bias-corrected C-index after internal validation was 0.748 in the training set. The calibration curves presented good concordance between the predicted and actual outcomes.

Conclusion

Centric pulmonary carcinoma and pericardial effusion were important independent risk factors for NOAF besides common ones in advanced lung cancer patients. Furthermore, the new nomogram model contributed to the prediction of NOAF.
Diverging prognostic effects of CD155 and CD73 expressions in locally advanced triple-negative breast cancer
Authors: Cabioglu Neslihan , Bayram Aysel , Emiroglu Selman , Onder Semen , Karatay Huseyin , Oner Gizem , Tukenmez Mustafa , Muslumanoglu Mahmut , Igci Abdullah , Aydiner Adnan , Saip Pinar , Yavuz Ekrem , Ozmen Vahit
Published: July 2023

Background

Immune checkpoint inhibition, combined with novel biomarkers, may provide alternative pathways for treating chemotherapy-resistant triple-negative breast cancer (TNBC). This study investigates the expression of new immune checkpoint receptors, including CD155 and CD73, which play a role in T and natural killer (NK) cell activities, in patients with residual TNBC after neoadjuvant chemotherapy (NAC).

Methods

The expression of biomarkers was immunohistochemically examined by staining archival tissue from surgical specimens (n = 53) using specific monoclonal antibodies for PD-L1, CD155, and CD73.

Results

Of those, 59.2% (29/49) were found to be positive (>1%) for PD-L1 on the tumour and tumour-infiltrating lymphocytes (TILs), while CD155 (30/53, 56.6%) and CD73 (24/53, 45.3%) were detected on tumours. Tumour expressions of CD155 and CD73 significantly correlated with PD-L1 expression on the tumour (p = 0.004 for CD155, p = 0.001 for CD73). Patients with CD155 positivity ≥10% were more likely to have a poor chemotherapy response, as evidenced by higher MDACC Residual Cancer Burden Index scores and Class II/III than those without CD155 expression (100% vs 82.6%, p = 0.03). At a median follow-up time of 80 months (range, 24–239), patients with high CD73 expression showed improved 10-year disease-free survival (DFS) and disease-specific survival (DSS) rates compared to those with low CD73 expression. In contrast, patients with CD155 (≥10%) expression exhibited a decreasing trend in 10-year DFS and DSS compared to cases with lower expression, although statistical significance was not reached. However, patients with coexpression of CD155 (≥10%) and low CD73 were significantly more likely to have decreased 10-year DFS and DSS rates compared to others (p = 0.005).

Conclusion

These results demonstrate high expression of CD73 and CD155 in patients with residual tumours following NAC. CD155 expression was associated with a poor response to NAC and poor prognosis in this chemotherapy-resistant TNBC cohort, supporting the use of additional immune checkpoint receptor inhibitor therapy. Interestingly, the interaction between CD155 and CD73 at lower levels resulted in a worse outcome than either marker alone, which calls for further investigation in future studies.
Partial preservation of the normal thyroid gland based on tumor diameter may be possible in small medullary thyroid carcinoma: a two-center 15-year retrospective study
Authors: Fu Guiming , Li Xiaoyi , Guo Fengli , Ruan Xianhui , Zhang Wei , Zhang Weijing , Zhang Yaping , Chen Yibo , Li Chunhua , Chen Jin , Zheng Xiangqian , Wang Zhaohui , Gao Ming
Published: July 2023

Background

At present, there are some controversies in the formulation of surgical protocol for small medullary thyroid carcinoma(s-MTC). We wanted to explore the feasibility of normal thyroid gland retention in small medullary thyroid carcinoma based on different tumor diameters and its prognostic impact on the tumor.

Methods

The data of patients with stage T1 MTC treated at Tianjin Cancer Hospital and Sichuan Cancer Hospital from 2006 to 2021 were analyzed. The tumor diameters of 0.5 cm and 1.0 cm were used as dividing points. The outcomes were tumor recurrence, metastasis, or patient death. Survival was estimated by the Kapan–Meier curve.

Results

A total of 121 T1 s-MTC patients were included, including 55 with total thyroidectomy (TT) and 66 with subthyroidectomy (Sub-TT). There were eleven cases of tumor recurrence and metastasis, and four patients died. When the tumor diameter was 1.0 cm as the cut-off point, tumor diameter (p = 0.010), TT (p = 0.028), unilateral and bilateral type (p = 0.009), and TNM staging (p = 0.007) had significant effects on progression-free survival (PFS). The tumor diameter, unilateral and bilateral type, and TT were risk factors for the prognosis of T1 MTC (p < 0.05).

Conclusion

The tumor diameter of 1.0 cm can be used as a cut-off point for stage T1 MTC. Alt-hough there was no significant difference in overall survival (OS) between T1a and T1b in patients, tumor diameter significantly influenced PFS. TT is not necessary for patients with sporadic MTC with T1a.
Development of a novel humanized mouse model to study bronchopulmonary dysplasia
Authors: Birkett Rob , Newar Janu , Sharma Abhineet M. , Lin Erika , Blank Lillian , Swaminathan Suchitra , Misharin Alexander , Mestan Karen K.
Published: July 2023

Rationale

The role of circulating fetal monocytes in bronchopulmonary dysplasia is not known. We utilized a humanized mouse model that supports human progenitor cell engraftment (MISTRG) to test the hypothesis that prenatal monocyte programming alters early lung development and response to hyperoxia.

Methods

Cord blood-derived monocytes from 10 human infants were adoptively transferred into newborn MISTRG mice at p0 (1 × 106 cells/mouse, intrahepatic injection) followed by normoxia versus hyperoxia (85% oxygen × 14 days). Lungs were harvested at p14 for alveolar histology (alveolar count, perimeter and area) and vascular parameters (vWF staining for microvessel density, Fulton's index). Human CD45 staining was conducted to compare presence of hematopoietic cells. Murine lung parameters were compared among placebo and monocyte-injected groups. The individual profiles of the 10 patients were further considered, including gestational age (GA; n = 2 term, n = 3 moderate/late preterm, and n = 5 very preterm infants) and preeclampsia (n = 4 patients). To explore the monocyte microenvironment of these patients, 30 cytokines/chemokines were measured in corresponding human plasma by multiplex immunoassay.

Results

Across the majority of patients and corresponding mice, MISTRG alveolarization was simplified and microvessel density was decreased following hyperoxia. Hyperoxia-induced changes were seen in both placebo (PBS) and monocyte-injected mice. Under normoxic conditions, alveolar development was altered modestly by monocytes as compared with placebo (P < 0.05). Monocyte injection was associated with increased microvessel density at P14 as compared with placebo (26.7 ± 0.73 vs. 18.8 ± 1.7 vessels per lung field; P < 0.001). Pooled analysis of patients revealed that injection of monocytes from births complicated by lower GA and preeclampsia was associated with changes in alveolarization and vascularization under normoxic conditions. These differences were modified by hyperoxia. CD45+ cell count was positively correlated with plasma monocyte chemoattractant protein-1 (P < 0.001) and macrophage inflammatory protein-1β (P < 0.01). Immunohistochemical staining for human CD206 and mouse F4/80 confirmed absence of macrophages in MISTRG lungs at P14.

Conclusions

Despite the inherent absence of macrophages in early stages of lung development, immunodeficient MISTRG mice revealed changes in alveolar and microvascular development induced by human monocytes. MISTRG mice exposed to neonatal hyperoxia may serve as a novel model to study isolated effects of human monocytes on alveolar and pulmonary vascular development.
Efficacy and safety of bevacizumab in patients with malignant melanoma: a systematic review and PRISMA-compliant meta-analysis of randomized controlled trials and non-comparative clinical studies
Authors: Han Xiao , Ge Pu , Liu Siyu , Yang Dandan , Zhang Jinzi , Wang Xinpei , Liang Weiting
Published: July 2023

Background: Malignant melanoma is a highly aggressive cancer that spreads and metastasizes quickly. In recent years, the antiangiogenic drug bevacizumab has been trialed to treat malignant melanoma. We conducted the first meta-analysis to examine the efficacy and safety of bevacizumab combined with other drugs in malignant melanoma.

Methods: We searched for randomized controlled trials (RCTs) and non-comparative clinical studies of bevacizumab combined with chemotherapy, targeted medicine, and interferon to treat malignant melanoma in PubMed, Embase, the Cochrane Library, and Web of Science. Meta-analysis of RCT was performed using Review Manager (version 5.4), and non-comparative meta-analysis was performed using R (version 4.0.3). The primary outcome was the objective response rate. Depending on the heterogeneity of the included studies, the pooled outcomes and 95% CI were calculated using either random-effects or fixed-effect models. Subgroup outcomes were calculated with possible relevant variables. Sensitivity analyses were carried out by excluding each study from the highly heterogeneous pooled results in turn. Funnel plot and Begg’s test were used to test the included studies' potential publication bias. The level of significance was set at p < 0.05.

Results: This meta-analysis included 20 trials: five RCTs and 15 non-comparative clinical studies with a total of 23 bevacizumab intervention arms. In 14 treatment arms, bevacizumab was combined with chemotherapy drugs such as fotemustine, dacarbazine, carboplatin/paclitaxel, and temozolomide. In six treatment arms, bevacizumab was combined with targeted medicines such as imatinib, everolimus, sorafenib, erlotinib, and temsirolimus. There were also six treatment arms that used bevacizumab in combination with interferon. The pooled objective response rate was 15.8% (95% CI, 11.4%–20.2%). Bevacizumab plus carboplatin/paclitaxel significantly increased the overall survival compared to carboplatin/paclitaxel (HR = 0.64, 95% CI, 0.49-0.85, p < 0.01). Fatigue, nausea, leukopenia, thrombocytopenia, and neutropenia were the most common adverse events. The pooled incidence of hypertension of all bevacizumab arms in malignant melanoma was 32.4% (95% CI, 24.5%–40.3%).

Conclusion: This study showed that bevacizumab combined with chemotherapy might be effective and well-tolerated in patients with stage III or IV unresectable malignant melanoma.

Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=304625], identifier [CRD42022304625].
Effect of anlotinib combined with ticeorgio for recurrent nasopharyngeal carcinoma: a case report
Authors: Mao Jiwei , Ye Wanli , Wu Dongping , Liu Jianjiang , Li Ting , Ma Weili , Zhou Yang
Published: July 2023

For patients with locally unresectable recurrent nasopharyngeal carcinoma who relapsed after 2 years of radiotherapy, re-radiotherapy is also the preferred treatment. However, for patients relapsed within 2 years, the use of re-radiotherapy would be greatly limited by its adverse effects. Consequently, finding a new strategy to prolong the time of re-radiotherapy for locally recurrent nasopharyngeal carcinoma is very necessary to reduce the related side effects and improve the curative effect. Anlotinib is an orally available small molecule multi-target tyrosine kinase inhibitor that primarily inhibits VEGFR2/3, FGFR1–4, PDGFR α/β, c-Kit, and Ret. However, whether recurrent nasopharyngeal carcinoma patients can be treated with anlotinib combined with ticeorgio (also called S-1) remains unknown. Herein, we report a nasopharyngeal carcinoma patient with local recurrence after radical radiotherapy who benefited from combination treatment of anlotinib with ticeorgio.
A novel nussbaum functions based adaptive event-triggered asymptotic tracking control of stochastic nonlinear systems with strong interconnections
Authors: Gao Yahui , Liu Chaoda , Guo Zhihua , Niu Ben , Zhang Baoyi
Published: July 2023

In this work, the issue of event-triggered-based asymptotic tracking adaptive control of stochastic nonlinear systems in pure-feedback form with strong interconnections is considered. First, a new decentralized control scheme is developed by introducing the new types of Nussbaum functions, which enables the output of each subsystem to asymptotically track the desired reference signal. Second, the nonaffine structures and the unknown control gains existing in the nonlinear systems are a part of the considered system model, which makes it more complicated to design the decentralized controllers. Therefore, the complexity caused by the nonaffine structures is faciliated by mean value theorem and the unknown control gains are handled by a novel Nussbaum function in our proposed design scheme. Meanwhile, the unknown nonlinearities of the system are approximated by using intelligent control technology. Furthermore, an event-triggered method is introduced in the design process to save communication resources effectively. It is shown that all signals of the closed-loop systems are bounded in probability and the tracking errors asymptotically converge to zero in probability. Finally, the simulation results illustrate the effectivity of the presented scheme.
Identification and functional analysis of αB-crystallins in Pteromalus puparum
Authors: Lao Shuxing , Xiong Shijiao , Fang Qi , Ye Gongyin
Published: July 2023

Heat shock proteins, including αB-crystallins (CRYAB), are pivotal in cellular defense mechanisms and stress response. This study presents a comprehensive investigation of heat shock proteins (HSPs), with a specific focus on the CRYAB family, within the genome of Pteromalus puparum. The analysis encompasses the identification of these proteins, exploration of their phylogenetic relationships, examination of conserved domains, and evaluation of their response to high temperature conditions. A total of 46 HSPs were identified in the P. puparum genome, and the differential expression of mRNA at 35°C and 25°C drew attention to five genes belonging to the CRYAB family, namely, PpCRYAB-1 to PpCRYAB-5. The conservation level of CRYAB family genes across different species was observed to be relatively modest. Through genome-wide screening of 22 species representing six insect orders, a total of 235 CRYAB proteins were identified, with P. puparum harboring eight CRYAB proteins, indicative of a moderate abundance compared to other species. Intriguingly, evolutionary analysis highlighted PpCRYAB-4 with potentially intricate differentiation in comparison to other members of the CRYAB family. Furthermore, RNA interference (RNAi) results demonstrated significant regulatory effects on adult lifespan under heat stress at 35°C for PpCRYAB-4 and PpCRYAB-5. These findings lay a groundwork for future investigations into stress resistance mechanisms in parasitic wasps, providing fresh insights for the study of insect resilience amidst the backdrop of global climate change.
Integration of physiology in a curriculum on human structure: a snapshot of the cardiovascular block
Authors: Bassey Rosemary B. , Hill Robert V. , Rennie William P.
Published: July 2023

With the gradual shift from discipline-based to competency-based medical education, the integrated curriculum has become a popular model for connecting basic science and clinical content in undergraduate medical education. Despite its popularity, there are concerns that important physiological concepts are not adequately addressed. We describe the spiral integration of physiology content in the 5-week Cardiovascular block of our Homeostasis course at the Zucker School of Medicine. We also describe our approach to incorporating physiology into an integrated, constructed response, short-answer assessment format. Our approach to spiral integration consists of rotating lab stations that highlight the distinction between normal and abnormal states, linked with appropriate clinical interventions. Physiology is at the core of integration in any curriculum and the basis of all applied fields of medicine, hence our approach is that teaching structural relationships would not be valuable without consideration of its functions, which can then be utilized in discussion of clinical presentations, imaging, and relevant pathologies. Likewise, our integrated assessments require the students to compose their answers to the questions from scratch, which creates a shift in mode of students’ preparation from rote memorizations to more cognitive processing that enhances critical thinking.
Seasonal variation in soil algal community structure in different forest plantations in subtropic China
Authors: Wei Liman , Zhao Qiong , Chen Xiangyu , Sun Qingye , Zhang Xiang , Chen Yongjing
Published: July 2023

Algae exert great impact on soil formation and biogeochemical cycling. However, there is no full understanding of the response of soil algal community structure to the seasonal fluctuations in temperature and moisture and changes of soil physicochemical properties across different forests. Here, based on 23S rRNA gene sequencing, we analyzed soil algal community structure in four different forest plantations in two seasons and examined soil physiochemical properties. The results showed the significantly seasonal variation in soil algal community structure, with the higher overall diversity in summer than in winter. In addition, there existed significant correlations between soil algae (species composition, relative abundance, diversity index) and physicochemical properties (pH, total phosphorus, organic matter and nitrate nitrogen), suggesting that edaphic characteristics are also largely responsible for the variation in soil algal community. Nevertheless, the seasonal variation in algal community structure was greater than the variation across different forest plantations. This suggest temperature and moisture are more important than soil physicochemical properties in determining soil algal community structure. The findings of the present study enhance our understanding of the algal communities in forest ecosystems and are of great significance for the management and protection of algal ecosystem.
From endodormancy to ecodormancy: the transcriptional landscape of apple floral buds
Authors: Sapkota Sangeeta , Salem Mohamed , Jahed Khalil R. , Artlip Timothy S. , Sherif Sherif M.
Published: July 2023

This study endeavors to explore the transcriptomic profiles of two apple cultivars, namely, ‘Honeycrisp’ and ‘Cripps Pink,’ which represent late and early-blooming cultivars, respectively. Using RNA-sequencing technology, we analyzed floral bud samples collected at five distinct time intervals during both endodormancy and ecodormancy. To evaluate the transcriptomic profiles of the 30 sequenced samples, we conducted principal component analysis (PCA). PC1 explained 43% of the variance, separating endodormancy and ecodormancy periods, while PC2 explained 16% of the variance, separating the two cultivars. The number of differentially expressed genes (DEGs) increased with endodormancy progression and remained elevated during ecodormancy. The majority of DEGs were unique to a particular time point, with only a few overlapping among or between the time points. This highlights the temporal specificity of gene expression during the dormancy transition and emphasizes the importance of sampling at multiple time points to capture the complete transcriptomic dynamics of this intricate process. We identified a total of 4204 upregulated and 7817 downregulated DEGs in the comparison of endodormancy and ecodormancy, regardless of cultivar, and 2135 upregulated and 2413 downregulated DEGs in the comparison of ‘Honeycrisp’ versus ‘Cripps Pink,’ regardless of dormancy stage. Furthermore, we conducted a co-expression network analysis to gain insight into the coordinated gene expression profiles across different time points, dormancy stages, and cultivars. This analysis revealed the most significant module (ME 14), correlated with 1000 GDH and consisting of 1162 genes. The expression of the genes within this module was lower in ‘Honeycrisp’ than in ‘Cripps Pink.’ The top 20 DEGs identified in ME 14 were primarily related to jasmonic acid biosynthesis and signaling, lipid metabolism, oxidation-reduction, and transmembrane transport activity. This suggests a plausible role for these pathways in governing bud dormancy and flowering time in apple.
High light-induced changes in whole-cell proteomic profile and its correlation with the organization of thylakoid super-complex in cyclic electron transport mutants of Chlamydomonas reinhardtii
Authors: Yadav Ranay Mohan , Marriboina Sureshbabu , Zamal Mohammad Yusuf , Pandey Jayendra , Subramanyam Rajagopal
Published: July 2023

Light and nutrients are essential components of photosynthesis. Activating the signaling cascades is critical in starting adaptive processes in response to high light. In this study, we have used wild-type (WT), cyclic electron transport (CET) mutants like Proton Gradient Regulation (PGR) (PGRL1), and PGR5 to elucidate the actual role in regulation and assembly of photosynthetic pigment–protein complexes under high light. Here, we have correlated the biophysical, biochemical, and proteomic approaches to understand the targeted proteins and the organization of thylakoid pigment–protein complexes in the photoacclimation. The proteomic analysis showed that 320 proteins were significantly affected under high light compared to the control and are mainly involved in the photosynthetic electron transport chain, protein synthesis, metabolic process, glycolysis, and proteins involved in cytoskeleton assembly. Additionally, we observed that the cytochrome (Cyt) b6 expression is increased in the pgr5 mutant to regulate proton motive force and ATPase across the thylakoid membrane. The increased Cyt b6 function in pgr5 could be due to the compromised function of chloroplast (cp) ATP synthase subunits for energy generation and photoprotection under high light. Moreover, our proteome data show that the photosystem subunit II (PSBS) protein isoforms (PSBS1 and PSBS2) expressed more than the Light-Harvesting Complex Stress-Related (LHCSR) protein in pgr5 compared to WT and pgrl1 under high light. The immunoblot data shows the photosystem II proteins D1 and D2 accumulated more in pgrl1 and pgr5 than WT under high light. In high light, CP43 and CP47 showed a reduced amount in pgr5 under high light due to changes in chlorophyll and carotenoid content around the PSII protein, which coordinates as a cofactor for efficient energy transfer from the light-harvesting antenna to the photosystem core. BN-PAGE and circular dichroism studies indicate changes in macromolecular assembly and thylakoid super-complexes destacking in pgrl1 and pgr5 due to changes in the pigment–protein complexes under high light. Based on this study, we emphasize that this is an excellent aid in understanding the role of CET mutants in thylakoid protein abundances and super-complex organization under high light.
The asymmetric photosynthetic characteristics of the isobilateral sorghum leaves under the illumination of the diffuse light
Authors: Wang Xiaolin , Wu Tao , Asim Muhammad , Ling Aifen , Sun Yanguo , Shi Yi , Yan Huifeng
Published: July 2023

The difference between photosynthesis on the two leaf sides (dorsoventral asymmetry) of photosynthesis is important for light-use patterns, but the asymmetry is environment dependent. Its role in photosynthetic regulation has been intensively studied, but little is known about the impacts of direct and diffuse light on the asymmetry. Because of the current changing fraction of diffuse light in sky radiation, this study investigated the dorsoventral asymmetry of photosynthetic traits under direct and diffuse light conditions in an important food and energy crop, Sorghum bicolor L. A unique method was used to investigate the specific gas exchange of each leaf surface. Anatomical and morphological traits were different between the two surfaces of sorghum leaves, which might result in photosynthetic asymmetry. The variations in photosynthetic rates and stomatal conductance were significant between the two surfaces in direct and diffuse light, but the degree of dorsoventral asymmetry decreased in diffuse light. The integrated PN and Gs of the adaxial illumination were significantly higher than that of abaxial illumination both in direct and diffuse light in sorghum leaves, but the ASI of the integrated PNwas 2.83 in direct light, while significantly dropped to 1.69 in diffuse light. Significant morphological differences between the two surfaces might cause photosynthetic asymmetry in the sorghum leaves. The variations of specific gas exchange were significant between direct and diffuse light, including in the incident and self-transmitted light. Compared with direct light, diffuse light reduced the stomatal sensitivity, with the degree of decline being greater in the adaxial surface, which caused weak dorsoventral asymmetry in photosynthesis. The specific photosynthetic characteristics in sorghum leaves varied obviously in direct and diffuse light, including in the incident and self-transmitted light, which contributed to the different overall gas exchange. Compared with direct light, the decline of stomatal sensitivity, which showed positive correlation with stomatal density, caused weakened dorsoventral asymmetry in photosynthesis in diffuse light. The findings provide new insights into dorsoventral asymmetry and the impact of diffuse light on photosynthesis in isobilateral leaves.
What do mathematics lessons look like? Analyses of primary students’ drawings
Authors: Rott Benjamin , Barton Laura , Hatisaru Vesife
Published: July 2023

The use of student drawings to assess their experiences and beliefs about teaching and learning of mathematics has become almost a regular research method – especially when working with young students who may not express themselves well, for example, in self-report questionnaires. These methods, nevertheless, need to be improved regarding their objectivity and validity. By building on the existing research, in this study, we focus on objectivity and validity issues in drawing-based methods. We use a drawing-based instrument: Draw A Mathematics Classroom (DAMC) and present 104 fourth-grade students to draw a picture of their regular mathematics lessons. We especially aim to develop and validate a data coding manual with low-inferent categories; that is, well-operationalizable categories that can be used with high interrater-reliability like the presence of teachers, the arrangement of student desks, and teacher-student interactions. The results reveal that almost half of the participating students perceive their lessons as teacher-centered. The results also confirm the reliability and validity of the methodological approach. For example, in pictures where the teacher is depicted larger than the students, the teacher is also depicted in the center, and students are pictured working alone. Classroom observations support students’ perceptions, and all these show that the manual used in this study is useful to getting insights into young students’ perceptions of their mathematics classroom.
Moving beyond the lab: investigating empathy through the Empirical 5E approach
Authors: Troncoso Alejandro , Soto Vicente , Gomila Antoni , Martínez-Pernía David
Published: July 2023

Empathy is a complex and multifaceted phenomenon that plays a crucial role in human social interactions. Recent developments in social neuroscience have provided valuable insights into the neural underpinnings and bodily mechanisms underlying empathy. This methodology often prioritizes precision, replicability, internal validity, and confound control. However, fully understanding the complexity of empathy seems unattainable by solely relying on artificial and controlled laboratory settings, while overlooking a comprehensive view of empathy through an ecological experimental approach. In this article, we propose articulating an integrative theoretical and methodological framework based on the 5E approach (the “E”s stand for embodied, embedded, enacted, emotional, and extended perspectives of empathy), highlighting the relevance of studying empathy as an active interaction between embodied agents, embedded in a shared real-world environment. In addition, we illustrate how a novel multimodal approach including mobile brain and body imaging (MoBi) combined with phenomenological methods, and the implementation of interactive paradigms in a natural context, are adequate procedures to study empathy from the 5E approach. In doing so, we present the Empirical 5E approach (E5E) as an integrative scientific framework to bridge brain/body and phenomenological attributes in an interbody interactive setting. Progressing toward an E5E approach can be crucial to understanding empathy in accordance with the complexity of how it is experienced in the real world.