bluuebunny/crossref_metadata_2025 huggingface dataset:
Toripalimab in combination with Anlotinib for unresectable hepatocellular carcinoma after SBRT: A prospective, single-arm, single-center clinical study
Authors: Chen Yongbiao , Hong Hanyin , Fang Wenzheng , Zhang Xia , Luo Huachun , Chen Zhijian , Yu Jianda , Fan Weiqiang , Chi Xiaobin , Peng Yonghai
Published: March 2023

Objective

Exposing tumor antigens to the immune system is the key to ensuring the efficacy of immunotherapy. SBRT is the main way to reveal the specifical antigens of tumors which can enhance the immune response. We aimed to explore the clinical efficacy and safety of Toripalimab combined with Anlotinib for uHCC after SBRT.

Methods

This is a prospective, single-arm, explorative clinical study. uHCC patients with an ECOG PS score of 0–1, Child–Pugh class A or B, and BCLC stage B or C were included and treated with SBRT(8Gy*3) followed by 6-cycle combinational therapy with Toripalimab and Anlotinib. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of treatment-related adverse events (TRAEs). Continuous variables were presented as medians and ranges. Survivals were studied with the Kaplan-Meier method. Categorical data were expressed as n (percentage).

Results

Between June 2020 and October 2022, a total of 20 patients with intermediate-advanced uHCC were enrolled. All cases had multiple intrahepatic metastases, or macrovascular invasion, or both, among whom 5 cases with lymph node or distant metastases. Until September 2022, the median follow-up time was 7.2 months (range, 1.1-27.7 months). Median survival time could not be assessed at the moment, based on iRecist, median PFS was 7.4 months (range, 1.1-27.7 months), ORR 15.0%, and DCR 50.0%. 14 patients experienced treatment-related adverse events with an incidence of 70%. The overall survival rates at 18 months and 24 months were 61.1% and 50.9%, respectively. And the progression-free survival rates were 39.3% and 19.7%.

Conclusion

Exposure of specific antigens of HCC via SBRT may improve the efficacy of combinational therapy with Toripalimab and Anlotinib for uHCC with manageable adverse effects, which deserves further exploration.

Clinical trial registration

www.clinicaltrials.gov, identifier ChiCTR2000032533.
Elevated temperatures and longer durations improve the efficacy of oxaliplatin- and mitomycin C-based hyperthermic intraperitoneal chemotherapy in a confirmed rat model for peritoneal metastasis of colorectal cancer origin
Authors: Helderman Roxan F. C. P. A. , Bokan Bella , van Bochove Gregor G. W. , Rodermond Hans M. , Thijssen Elsy , Marchal Wouter , Torang Arezo , Löke Daan R. , Franken Nicolaas A. P. , Kok H. Petra , Tanis Pieter J. , Crezee Johannes , Oei Arlene L.
Published: March 2023

Introduction

In patients with limited peritoneal metastasis (PM) originating from colorectal cancer, cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment option. This combined treatment modality using HIPEC with mitomycin C (MMC) for 90 minutes proved to be superior to systemic chemotherapy alone, but no benefit of adding HIPEC to CRS alone was shown using oxaliplatin-based HIPEC during 30 minutes. We investigated the impact of treatment temperature and duration as relevant HIPEC parameters for these two chemotherapeutic agents in representative preclinical models. The temperature- and duration- dependent efficacy for both oxaliplatin and MMC was evaluated in an in vitro setting and in a representative animal model.

Methods

In 130 WAG/Rij rats, PM were established through i.p. injections of rat CC-531 colon carcinoma cells with a signature similar to the dominant treatment-resistant CMS4 type human colorectal PM. Tumor growth was monitored twice per week using ultrasound, and HIPEC was applied when most tumors were 4-6 mm. A semi-open four-inflow HIPEC setup was used to circulate oxaliplatin or MMC through the peritoneum for 30, 60 or 90 minutes with inflow temperatures of 38°C or 42°C to achieve temperatures in the peritoneum of 37°C or 41°C. Tumors, healthy tissue and blood were collected directly or 48 hours after treatment to assess the platinum uptake, level of apoptosis and proliferation and to determine the healthy tissue toxicity.

Results

In vitro results show a temperature- and duration- dependent efficacy for both oxaliplatin and MMC in both CC-531 cells and organoids. Temperature distribution throughout the peritoneum of the rats was stable with normothermic and hyperthermic average temperatures in the peritoneum ranging from 36.95-37.63°C and 40.51-41.37°C, respectively. Treatments resulted in minimal body weight decrease (<10%) and only 7/130 rats did not reach the endpoint of 48 hours after treatment.

Conclusions

Both elevated temperatures and longer treatment duration resulted in a higher platinum uptake, significantly increased apoptosis and lower proliferation in PM tumor lesions, without enhanced normal tissue toxicity. Our results demonstrated that oxaliplatin- and MMC-based HIPEC procedures are both temperature- and duration-dependent in an in vivo tumor model.
BRCA1-methylated triple negative breast cancers previously exposed to neoadjuvant chemotherapy form RAD51 foci and respond poorly to olaparib
Authors: Velazquez Carolina , Orhan Esin , Tabet Imene , Fenou Lise , Orsetti Béatrice , Adélaïde José , Guille Arnaud , Thézénas Simon , Crapez Evelyne , Colombo Pierre-Emmanuel , Chaffanet Max , Birnbaum Daniel , Sardet Claude , Jacot William , Theillet Charles
Published: March 2023

Background

About 15% of Triple-Negative-Breast-Cancer (TNBC) present silencing of the BRCA1 promoter methylation and are assumed to be Homologous Recombination Deficient (HRD). BRCA1-methylated (BRCA1-Me) TNBC could, thus, be eligible to treatment based on PARP-inhibitors or Platinum salts. However, their actual HRD status is discussed, as these tumors are suspected to develop resistance after chemotherapy exposure.

Methods

We interrogated the sensitivity to olaparib vs. carboplatin of 8 TNBC Patient-Derived Xenografts (PDX) models. Four PDX corresponded to BRCA1-Me, of which 3 were previously exposed to NeoAdjuvant-Chemotherapy (NACT). The remaining PDX models corresponded to two BRCA1-mutated (BRCA1-Mut) and two BRCA1-wild type PDX that were respectively included as positive and negative controls. The HRD status of our PDX models was assessed using both genomic signatures and the functional BRCA1 and RAD51 nuclear foci formation assay. To assess HR restoration associated with olaparib resistance, we studied pairs of BRCA1 deficient cell lines and their resistant subclones.

Results

The 3 BRCA1-Me PDX that had been exposed to NACT responded poorly to olaparib, likewise BRCA1-WT PDX. Contrastingly, 3 treatment-naïve BRCA1-deficient PDX (1 BRCA1-Me and 2 BRCA1-mutated) responded to olaparib. Noticeably, the three olaparib-responsive PDX scored negative for BRCA1- and RAD51-foci, whereas all non-responsive PDX models, including the 3 NACT-exposed BRCA1-Me PDX, scored positive for RAD51-foci. This suggested HRD in olaparib responsive PDX, while non-responsive models were HR proficient. These results were consistent with observations in cell lines showing a significant increase of RAD51-foci in olaparib-resistant subclones compared with sensitive parental cells, suggesting HR restoration in these models.

Conclusion

Our results thus support the notion that the actual HRD status of BRCA1-Me TNBC, especially if previously exposed to chemotherapy, may be questioned and should be verified using the BRCA1- and RAD51-foci assay.
Prognostic value and multifaceted roles of tetraspanin CD9 in cancer
Authors: Ondruššek Róbert , Kvokačková Barbora , Kryštofová Karolína , Brychtová Světlana , Souček Karel , Bouchal Jan
Published: March 2023

CD9 is a crucial regulator of cell adhesion in the immune system and plays important physiological roles in hematopoiesis, blood coagulation or viral and bacterial infections. It is involved in the transendothelial migration of leukocytes which might also be hijacked by cancer cells during their invasion and metastasis. CD9 is found at the cell surface and the membrane of exosomes affecting cancer progression and therapy resistance. High expression of CD9 is mostly associated with good patients outcome, with a few exceptions. Discordant findings have been reported for breast, ovarian, melanoma, pancreatic and esophageal cancer, which might be related to using different antibodies or inherent cancer heterogeneity. According to in vitro and in vivo studies, tetraspanin CD9 is not clearly associated with either tumor suppression or promotion. Further mechanistic experiments will elucidate the role of CD9 in particular cancer types and specific conditions.
Human gut, breast, and oral microbiome in breast cancer: A systematic review and meta-analysis
Authors: Thu May Soe , Chotirosniramit Korn , Nopsopon Tanawin , Hirankarn Nattiya , Pongpirul Krit
Published: March 2023

Introduction

Dysbiosis characterises breast cancer through direct or indirect interference in a variety of biological pathways; therefore, specific microbial patterns and diversity may be a biomarker for the diagnosis and prognosis of breast cancer. However, there is still much to determine about the complex interplay of the gut microbiome and breast cancer.

Objective

This study aims to evaluate microbial alteration in breast cancer patients compared with control subjects, to explore intestine microbial modification from a range of different breast cancer treatments, and to identify the impact of microbiome patterns on the same treatment-receiving breast cancer patients.

Methods

A literature search was conducted using electronic databases such as PubMed, Embase, and the CENTRAL databases up to April 2021. The search was limited to adult women with breast cancer and the English language. The results were synthesised qualitatively and quantitatively using random-effects meta-analysis.

Results

A total of 33 articles from 32 studies were included in the review, representing 19 case-control, eight cohorts, and five nonrandomised intervention researches. The gut and breast bacterial species were elevated in the cases of breast tumours, a significant increase in Methylobacterium radiotolerans (p = 0.015), in compared with healthy breast tissue. Meta-analysis of different α-diversity indexes such as Shannon index (p = 0.0005), observed species (p = 0.006), and faint’s phylogenetic diversity (p < 0.00001) revealed the low intestinal microbial diversity in patients with breast cancer. The microbiota abundance pattern was identified in different sample types, detection methods, menopausal status, nationality, obesity, sleep quality, and several interventions using qualitative analysis.

Conclusions

This systematic review elucidates the complex network of the microbiome, breast cancer, and therapeutic options, with the objective of providing a link for stronger research studies and towards personalised medicine to improve their quality of life.
Nociception in fruit fly larvae
Authors: Boivin Jean-Christophe , Zhu Jiayi , Ohyama Tomoko
Published: March 2023

Nociception, the process of encoding and processing noxious or painful stimuli, allows animals to detect and avoid or escape from potentially life-threatening stimuli. Here, we provide a brief overview of recent technical developments and studies that have advanced our understanding of the Drosophila larval nociceptive circuit and demonstrated its potential as a model system to elucidate the mechanistic basis of nociception. The nervous system of a Drosophila larva contains roughly 15,000 neurons, which allows for reconstructing the connectivity among them directly by transmission electron microscopy. In addition, the availability of genetic tools for manipulating the activity of individual neurons and recent advances in computational and high-throughput behavior analysis methods have facilitated the identification of a neural circuit underlying a characteristic nocifensive behavior. We also discuss how neuromodulators may play a key role in modulating the nociceptive circuit and behavioral output. A detailed understanding of the structure and function of Drosophila larval nociceptive neural circuit could provide insights into the organization and operation of pain circuits in mammals and generate new knowledge to advance the development of treatment options for pain in humans.
Adaptations of the Walking Corsi Test (WalCT) for 2- and 3-year-old preterm and term-born toddlers: A preliminary study
Authors: Martín-Pozuelo Nuria , Robles-García Verónica , Piccardi Laura , Quintela del Rio Alejandro , Cudeiro Javier , De las Cuevas-Terán Isabel
Published: March 2023

Introduction

Topographical memory is crucial for navigation and environmental representation. The Walking Corsi Test (WalCT) has been used to evaluate topographical memory in children from 4 years upward. The present study aims to determine whether adapted versions of the WalCT- by simplifying instructions and increasing motivation- can be adopted to test topographical memory in 2- and 3-year-old toddlers born at term and preterm. Assessing this skill in such young children is important in light of recent studies that have shown how spatial cognition underlies the development of skills in other cognitive domains as well. Methods: For this purpose, 47 toddlers (27.39 ± 4.34 months, 38.3% females), 20 born at term and 27 preterm, performed two aimed-designed versions of WalCT.

Results

The results showed better performance of the term groups with increasing age and for both versions. On the other hand, performance was better in 2-year-old term toddlers vs. preterm. When rising motivation, 2-year-old preterm toddlers improve their performance but differences between both groups were still significant. The preterm group showed lower performance related to lower levels of attention.

Discussion

This study provides preliminary data on the suitability of the adapted versions of WalCT in early ages and prematurity conditions.
Case report: Progressive skin rash and lymphadenopathy associated with lamotrigine−valproic acid combination in a bipolar adolescent
Authors: Duan Yingxu , Qiu Fangxinrui , Zhou Jingyuan , Liu Shiyu , Zhao Die , Qiu Changjian
Published: March 2023

Background: Lamotrigine may cause severe skin reactions. There is a known interaction between lamotrigine and valproic acid with an increase in lamotrigine levels and lamotrigine toxicity risk. Few cases of severe rash and systemic reactions in bipolar patients using lamotrigine and valproate have been reported. Here, we report a rare case of severe skin rash and lymphadenopathy associated with lamotrigine−valproic acid combination.

Case presentation: An 18-year-old female adolescent with bipolar disorder type I was treated with lamotrigine, magnesium valproate, and perospirone for 12 days. After the last dose of lamotrigine, she abruptly developed generalized rash and swollen lymph nodes, which continued to progress over the next 3 days. This finally subsided after stopping valproate and with glucocorticoid treatment.

Conclusion: This case suggests that lamotrigine−valproic acid combination may cause not only rash but also lymphadenopathy. Even though the aforementioned reactions appear after the last dose of lamotrigine, it cannot be ruled out as suspicious. We recommend caution during titration of lamotrigine and valproate and early withdrawal of both when signs of hypersensitivity appear.
Modified 5-aminolevulinic acid photodynamic therapy suppresses cutaneous squamous cell carcinoma through blocking Akt/mTOR-mediated autophagic flux
Authors: Zeng Qingyu , Liu Jia , Yan Yu , Zhang Guolong , Wang Periru , Zhang Haiyan , Liu Xiaojing , Zhang Linglin , Wang Xiuli
Published: March 2023

Background: We previously found that modified 5-aminolevulinic acid photodynamic therapy (M-PDT) is painless and effective in cutaneous squamous cell carcinoma (cSCC) treatment, however, the regulatory mechanism of M-PDT in cSCC is still unclear.

Objective: To clarify the effect and relevant regulatory mechanism of M-PDT in cSCC.

Methods: The cSCC apoptosis was examined by flow cytometry, TUNEL staining and Cleaved-caspase-3 immunofluorescence, respectively. The autophagy-related characterization was detected by monodansylcadaverine (MDC) staining, transmission electron microscopy (TEM), GFP-LC3B autophagic vacuoles localization and mRFP-EGFP tandem fluorescence-tagged LC3B construct, respectively. The expression of autophagy-related proteins and Akt/mTOR signaling molecules were examined by Western blot. ROS generation was measured by DCFH-DA probe.

Results: We found that M-PDT induced cSCC apoptosis in a dose-dependent manner, and this result was related to autophagic flux blockage. The phenomenon is confirmed by the results that M-PDT could induce autophagosomes accumulation and upregulate LC3-II and p62 expression. M-PDT elevated co-localization of RFP and GFP tandem-tagged LC3B puncta in cSCC cell, reflecting autophagic flux blockage, and this was confirmed by transmission electron microscopy. Furthermore, we noticed that M-PDT induced accumulated autophagosomes-dependent apoptosis via targeting ROS-mediated Akt/mTOR signaling. Suppression of Akt potentiated M-PDT-induced upregulation of LC3-II and p62 levels, whereas Akt activation and ROS inhibition rendered resistance to these events. In addition, we observed that lysosomal dysfunction was involved in M-PDT-triggered accumulated autophagosomes-dependent cSCC apoptosis.

Conclusion: Our data demonstrates that M-PDT inhibits cSCC through blocking Akt/mTOR-mediated autophagic flux.
Sales trends of psychotropic drugs in the COVID-19 pandemic: A national database study in Brazil
Authors: Del Fiol Fernando de Sá , Bergamaschi Cristiane de Cássia , Lopes Luciane Cruz , Silva Marcus Tolentino , Barberato-Filho Silvio
Published: March 2023

Background: The social restrictions among coronavirus disease 2019 (COVID-19) pandemic have posed a thoughtful risk to mental health and have implications in the use of drugs, including antidepressants, anxiolytics and other psychotropics.

Objective: This study analyzed the sales data of the psychotropics prescribed in Brazil, in order to verify the change in consumption trends of these drugs during the COVID-19 pandemic.

Methods: This interrupted time-series analyzed psychotropic sales data, between January 2014 and July 2021, using the National System of Controlled Products Management from The Brazilian Health Regulatory Agency. The monthly mean DDDs per 1,000 inhabitants per day of psychotropic drugs was evaluated by analysis of variance (ANOVA) followed by Dunnett Multiple Comparisons Test. The changes in monthly trends in the use of the psychotropic studied were evaluated by Joinpoint regression.

Results: During the period studied, clonazepam, alprazolam, zolpidem and escitalopram were the most sold psychotropic drugs in Brazil. According to Joinpoint regression, an upward trend was observed in sales during the pandemic of pregabalin, escitalopram, lithium, desvenlafaxine, citalopram, buproprion and amitriptyline. An increase in psychotropic consumption was noted throughout the pandemic period, with the maximum consumption (2.61 DDDs) occurring in April 2021, with a downward trend in consumption that accompanied the drop in the number of deaths.

Conclusions: The increase in sales, mainly of antidepressants during the COVID-19 pandemic, draws attention to issues related to the mental health of the Brazilian population and on the need for greater monitoring in the dispensing of these drugs.
Potent anti-inflammatory responses: Role of hydrogen in IL-1α dominated early phase systemic inflammation
Authors: Wei Youzhen , Wang Kun , Zhang Yafang , Duan Yi , Tian Yan , Yin Hongling , Fu Xuelian , Ma Zuan , Zhou Jianjun , Yu Min , Ni Qingbin , Tang Wenjie
Published: March 2023

Introduction: It has been proven that hydrogen has obvious anti-inflammatory effects in animal experiments and clinical practice. However, the early dynamic process of the inflammatory response caused by lipopolysaccharide (LPS) and the anti-inflammatory effect of hydrogen has not been definitively reported.

Methods: Inflammation in male C57/BL6J mice or RAW264.7 cells was induced with LPS, for which hydrogen was immediately administered until samples were taken. Pathological changes in lung tissue were assessed using hematoxylin and eosin (HE) staining. Levels of inflammatory factors in serum were determined using liquid protein chip. The mRNA levels of chemotactic factors in lung tissues, leukocytes, and peritoneal macrophages were measured by qRT-PCR. The expression levels of IL-1α and HIF-1α were measured by immunocytochemistry.

Results: Hydrogen alleviated LPS-induced inflammatory infiltration in the lung tissues of mice. Among the 23 inflammatory factors screened, LPS-induced upregulation of IL-1α etc. was significantly inhibited by hydrogen within 1 hour. The mRNA expression of MCP-1, MIP-1α, G-CSF, and RANTES was inhibited obviously by hydrogen at 0.5 and 1 h in mouse peritoneal macrophages. In addition, hydrogen significantly blocked LPS or H2O2-induced upregulation of HIF-1α, and IL-1α in 0.5 h in RAW264.7 cells.

Discussion: The results suggested that hydrogen is potentially inhibitive against inflammation by inhibiting HIF-1α and IL-1α release at early occurrence. The target of the inhibitive LPS-induced-inflammatory action of hydrogen is chemokines in macrophages in the peritoneal cavity. This study provides direct experimental evidence for quickly controlling inflammation with the translational application of a hydrogen-assisted protocol.
Discrimination between human normal renal tissue and renal cell carcinoma by dielectric properties using in-vitro BIA
Authors: Wang Hang , Shi Xuetao , Cao Xinsheng , Dong Xiuzhen , Yang Lin
Published: March 2023

Renal cell carcinoma (RCC) poses a serious threat to human health, which urgently requires a method that can quickly distinguish between human normal renal tissue (NRT) and RCC for the purpose of accurate detection in clinical practice. The significant difference in cell morphology between NRT and RCC tissue underlies the great potential of the bioelectrical impedance analysis (BIA) to distinguish two types of human tissues. The study aims to achieve such discrimination through comparison of their dielectric properties within the frequency range from 10 Hz to 100 MHz. The dielectric properties of 69 cases of human normal and cancer renal tissue were measured 15 min after tissue isolation in a strictly controlled environment (37°C, 90% humidity). In addition to the impedance parameters (resistivity, conductivity and relative permittivity), the characteristic parameters extracted from the Cole curve were also compared between NRT and RCC. Furthermore, a novel index, distinguishing coefficient (DC), was used to obtain the optimal frequency for discrimination between NRT and RCC. In terms of impedance parameters, the RCC conductivity at low frequencies (<1 kHz) was about 1.4 times as large as that of NRT, and its relative permittivity was also significantly higher (p < 0.05). In terms of characteristic parameters, two characteristic frequencies (14.1 ± 1.1 kHz and 1.16 ± 0.13 MHz) were found for NRT while only one for RCC (0.60 ± 0.05 MHz). A significant difference of low-frequency resistance (R0) between RCC and NRT was also observed (p < 0.05). As for the new index DC, relative permittivity DCs below 100 Hz and at around 14 kHz were both greater than 1. These findings further confirm the feasibility of discrimination between RCC and NRT and also provide data in favor of further clinical study of BIA to detect the surgical margins.
Stress induced proinflammatory adaptations: Plausible mechanisms for the link between stress and cardiovascular disease
Authors: Slusher Aaron L. , Acevedo Edmund O.
Published: March 2023

Initiating from Hans Selye’s conceptualization of stress physiology, to our present understanding of allostatic load as the cumulative burden of chronic psychological stress and life events, investigators have sought to identify the physiological mechanisms that link stress to health and disease. Of particular interest has been the link between psychological stress and cardiovascular disease (CVD), the number one cause of death in the United States. In this regard, attention has been directed toward alterations in the immune system in response to stress that lead to increased levels of systemic inflammation as a potential pathway by which stress contributes to the development of CVD. More specifically, psychological stress is an independent risk factor for CVD, and as such, mechanisms that explain the connection of stress hormones to systemic inflammation have been examined to gain a greater understanding of the etiology of CVD. Research on proinflammatory cellular mechanisms that are activated in response to psychological stress demonstrates that the ensuing low-grade inflammation mediates pathways that contribute to the development of CVD. Interestingly, physical activity, along with its direct benefits to cardiovascular health, has been shown to buffer against the harmful consequences of psychological stress by “toughening” the SAM system, HPA axis, and immune system as “cross-stressor adaptations” that maintain allostasis and prevent allostatic load. Thus, physical activity training reduces psychological stress induced proinflammation and attenuates the activation of mechanisms associated with the development of cardiovascular disease. Finally, COVID-19 associated psychological stress and its associated health risks has provided another model for examining the stress-health relationship.
Spaceflight alters reaction time and duration judgment of astronauts
Authors: Kuldavletova Olga , Navarro Morales Deborah C. , Quarck Gaëlle , Denise Pierre , Clément Gilles
Published: March 2023

We report a study on astronauts aimed at characterizing duration judgment before, during, and after long-duration stays on board the International Space Station. Ten astronauts and a control group of 15 healthy (non-astronaut) participants performed a duration reproduction task and a duration production task using a visual target duration ranging from 2 to 38 s. Participants also performed a reaction time test for assessing attention. Compared to control participants and preflight responses, the astronauts’ reaction time increased during spaceflight. Also, during spaceflight, time intervals were under-produced while counting aloud and under-reproduced when there was a concurrent reading task. We hypothesize that time perception during spaceflight is altered by two mechanisms: (a) an acceleration of the internal clock through the changes in vestibular inputs in microgravity, and (b) difficulties in attention and working memory when a concurrent reading task is present. Prolonged isolation in confined areas, weightlessness, stress related to workload, and high-performance expectations could account for these cognitive impairments.
Microtopography mediates the climate–growth relationship and growth resilience to drought of Pinus tabulaeformis plantation in the hilly site
Authors: Zhao Hongming , Wu Jiabing , Wang Anzhi , Guan Dexin , Liu Yage
Published: March 2023

Understanding the factors affecting the growth of plantation forests can reduce the loss of economic and ecological values caused by plantation forest subhealth. Plantation forests are widely distributed in hilly areas with microtopographic features. Microtopography influences climatic factors associated with plant growth, during not only general time but also extreme events like droughts. However, little research has been conducted on the effects of microtopography on the plantation forest growth. In this paper, we selected Pinus tabulaeformis planted in a hilly site, and studied the effect of microtopography on the climate–growth relationship and drought response of a typical plantation in Northeast China using dendroecological methods. We found: 1) Between hill positions, temperature caused a climatic growth difference. Compared to the hilltop, the correlation of annual growth on the hillside with monthly temperature was more negative in July–August and less positive in January–April. 2) Between aspects, precipitation intensities caused a climatic growth difference. Compared to the sunny slope, the correlation of annual growth on the shady slope with monthly total precipitation below 10 mm/day was less positive (May–June) or more negative (March–April and July), while that with monthly total precipitation above 10 mm/day was more positive in most months.3) Drought response varied significantly based on hill position and aspect. There was no significant difference in resistance between hill positions, while recovery and resilience on the hilltop were greater than those on the hillside.Resistance, recovery, and resilience were all lower on the sunny slope than those on the shady slope. Overall, microtopography exists the effects on the growth of plantation forests, both in terms of climate-growth relationships in general climate and in response to drought when extreme events. Meanwhile, the climatic factors that caused the difference in growth of plantation forests between hill positions and aspects differed. The difference in growth between hill positions was caused by temperature, while that between aspects was caused by precipitation intensity. Drought response difference reflected the legacy effect of drought on plantation growth, which could lead to subsequent changes in climate-growth relationships. These findings demonstrate that strengthening the research of forest trees on microtopography is necessary for accurate carbon sink assessment and precise forest management.
CRISPR-Cas9-mediated knockout of CYP79D1 and CYP79D2 in cassava attenuates toxic cyanogen production
Authors: Gomez Michael A. , Berkoff Kodiak C. , Gill Baljeet K. , Iavarone Anthony T. , Lieberman Samantha E. , Ma Jessica M. , Schultink Alex , Karavolias Nicholas G. , Wyman Stacia K. , Chauhan Raj Deepika , Taylor Nigel J. , Staskawicz Brian J. , Cho Myeong-Je , Rokhsar Daniel S. , Lyons Jessica B.
Published: March 2023

Cassava (Manihot esculenta) is a starchy root crop that supports over a billion people in tropical and subtropical regions of the world. This staple, however, produces the neurotoxin cyanide and requires processing for safe consumption. Excessive consumption of insufficiently processed cassava, in combination with protein-poor diets, can have neurodegenerative impacts. This problem is further exacerbated by drought conditions which increase this toxin in the plant. To reduce cyanide levels in cassava, we used CRISPR-mediated mutagenesis to disrupt the cytochrome P450 genes CYP79D1 and CYP79D2 whose protein products catalyze the first step in cyanogenic glucoside biosynthesis. Knockout of both genes eliminated cyanide in leaves and storage roots of cassava accession 60444; the West African, farmer-preferred cultivar TME 419; and the improved variety TMS 91/02324. Although knockout of CYP79D2 alone resulted in significant reduction of cyanide, mutagenesis of CYP79D1 did not, indicating these paralogs have diverged in their function. The congruence of results across accessions indicates that our approach could readily be extended to other preferred or improved cultivars. This work demonstrates cassava genome editing for enhanced food safety and reduced processing burden, against the backdrop of a changing climate.
Physiological and molecular mechanism of ginger (Zingiber officinale Roscoe) seedling response to salt stress
Authors: Liu Miaohong , Lv Yao , Cao Bili , Chen Zijing , Xu Kun
Published: March 2023

We used ‘Shannong No.1’ experimental material to simulate higher salt concentration in ginger and analyzed the physiological responses of different parts of ginger seedlings under salt stress. The results showed that salt stress led to a significant decrease in fresh and dry weight of ginger, lipid membrane peroxidation, increased sodium ion content and enhanced activity of antioxidant enzymes. Compared with the control, the overall plant dry weight of ginger under salt stress decreased by about 60%, and the MDA content in roots, stems, leaves, and rhizomes increased by 372.27%, 184.88%, 291.5%, and 171.13%, respectively, and the APX content increased by 188.85%, 165.56%, 195.38%, and 40.08%, respectively. After analysis of the physiological indicators, it was found that the roots and leaves of ginger were the most significantly changed parts. We analyzed the transcriptional differences between ginger roots and leaves by RNA-seq and found that they jointly initiated MAPK signaling pathways in response to salt stress. By combining physiological and molecular indicators, we elucidated the response of different tissues and parts of ginger to salt stress during the seedling stage.
Association of maize (Zea mays L.) senescence with water and nitrogen utilization under different drip irrigation systems
Authors: Wu Yang , Yao Fanyun , Wang Yongjun , Ma Lin , Li Xiangnan
Published: March 2023

Introduction

Drip irrigation is an efficient water-saving system used to improve crop production worldwide. However, we still lack a comprehensive understanding of maize plant senescence and its association with yield, soil water, and nitrogen (N) utilization under this system.

Methods

A 3-year field experiment in the northeast plains of China was used to assess four drip irrigation systems: (1) drip irrigation under plastic film mulch (PI); (2) drip irrigation under biodegradable film mulch (BI); (3) drip irrigation incorporating straw returning (SI); and (4) drip irrigation with the tape buried at a shallow soil depth (OI), and furrow irrigation (FI) was used as the control. The plant senescence characteristic based on the dynamic process of green leaf area (GLA) and live root length density (LRLD) during the reproductive stage, and its correlation with leaf N components, water use efficiency (WUE), and N use efficiency (NUE) was investigated.

Results

PI followed by BI achieved the highest integral GLA and LRLD, grain filling rate, and leaf and root senescence rate after silking. Greater yield, WUE, and NUE were positively associated with higher N translocation efficiency of leaf protein responding for photosynthesis, respiration, and structure under PI and BI; whereas, no significant differences were found in yield, WUE, and NUE between PI and BI. SI effectively promoted LRLD in the deeper 20- to 100-cm soil layers, prolonged the GLA and LRLD persistent durations, and reduced the leaf and root senescence rates. The remobilization of non-protein storage N was stimulated by SI, FI, and OI, which made up for the relative inadequacy of leaf N.

Discussion

Instead of persistent GLA and LRLD durations and high translocation efficiency of non-protein storage N, fast and large protein N translocation from leaves to grains under PI and BI was found to facilitate maize yield, WUE, and NUE in the sole cropping semi-arid region, and BI was recommend considering that it can reduce plastic pollution.
Identification of major QTLs for yield-related traits with improved genetic map in wheat
Authors: Ma Feifei , Xu Yunfeng , Wang Ruifang , Tong Yiping , Zhang Aimin , Liu Dongcheng , An Diaoguo
Published: March 2023

Introduction

Identification of stable major quantitative trait loci (QTLs) for yield-related traits is important for yield potential improvement in wheat breeding.

Methods

In the present study, we genotyped a recombinant inbred line (RIL) population using the Wheat 660K SNP array and constructed a high-density genetic map. The genetic map showed high collinearity with the wheat genome assembly. Fourteen yield-related traits were evaluated in six environments for QTL analysis.

Results and Discussion

A total of 12 environmentally stable QTLs were identified in at least three environments, explaining up to 34.7% of the phenotypic variation. Of these, QTkw-1B.2 for thousand kernel weight (TKW), QPh-2D.1 (QSl-2D.2/QScn-2D.1) for plant height (PH), spike length (SL) and spikelet compactness (SCN), QPh-4B.1 for PH, and QTss-7A.3 for total spikelet number per spike (TSS) were detected in at least five environments. A set of Kompetitive Allele Specific PCR (KASP) markers were converted based on the above QTLs and used to genotype a diversity panel comprising of 190 wheat accessions across four growing seasons. QPh-2D.1 (QSl-2D.2/QScn-2D.1), QPh-4B.1 and QTss-7A.3 were successfully validated. Compared with previous studies, QTkw-1B.2 and QPh-4B.1 should be novel QTLs. These results provided a solid foundation for further positional cloning and marker-assisted selection of the targeted QTLs in wheat breeding programs.
Constant hydraulic supply and ABA dynamics facilitate the trade-offs in water and carbon
Authors: Abdalla Mohanned , Schweiger Andreas H. , Berauer Bernd J. , McAdam Scott A. M. , Ahmed Mutez Ali
Published: March 2023

Carbon-water trade-offs in plants are adjusted through stomatal regulation. Stomatal opening enables carbon uptake and plant growth, whereas plants circumvent drought by closing stomata. The specific effects of leaf position and age on stomatal behavior remain largely unknown, especially under edaphic and atmospheric drought. Here, we compared stomatal conductance (gs) across the canopy of tomato during soil drying. We measured gas exchange, foliage ABA level and soil-plant hydraulics under increasing vapor pressure deficit (VPD). Our results indicate a strong effect of canopy position on stomatal behavior, especially under hydrated soil conditions and relatively low VPD. In wet soil (soil water potential > -50 kPa), upper canopy leaves had the highest gs (0.727 ± 0.154 mol m-2 s-1) and assimilation rate (A; 23.4 ± 3.9 µmol m-2 s-1) compared to the leaves at a medium height of the canopy (gs: 0.159 ± 0.060 mol m2 s-1; A: 15.9 ± 3.8 µmol m-2 s-1). Under increasing VPD (from 1.8 to 2.6 kPa), gs, A and transpiration were initially impacted by leaf position rather than leaf age. However, under high VPD (2.6 kPa), age effect outweighed position effect. The soil-leaf hydraulic conductance was similar in all leaves. Foliage ABA levels increased with rising VPD in mature leaves at medium height (217.56 ± 85 ng g-1 FW) compared to upper canopy leaves (85.36 ± 34 ng g-1 FW). Under soil drought (< -50 kPa), stomata closed in all leaves resulting in no differences in gs across the canopy. We conclude that constant hydraulic supply and ABA dynamics facilitate preferential stomatal behavior and carbon-water trade-offs across the canopy. These findings are fundamental in understanding variations within the canopy, which helps in engineering future crops, especially in the face of climate change.
The home language environment and early language ability in rural Southwestern China
Authors: Zhang Xinwu , Ma Yue , Feng Tianli , Zhang Vincent , Wu Xiaoyang , Li Matthew , Li Queenie , Thani Zahra , Pappas Lucy , Dill Sarah-Eve , Rozelle Scott
Published: March 2023

Using premier Language Environment Analysis technology to measure and analyze the home language environment, this observational study aims to describe the home language environment and child language ability, drawing on empirical data from 77 households with children aged 18–24 months from rural China. The results show large variation in measures of the home language environment and early language ability, similar to other rural Chinese samples. Results also demonstrate significant correlations between child age and the home language environment, maternal employment and the home language environment, father’s educational attainment and the home language environment, adult–child conversations and early language ability, and child vocalizations and early language ability.
Monitoring system of implementation of the Promoting Mental Health at Schools (PROMEHS) program
Authors: Martinsone Baiba , Stokenberga Ieva , Grazzani Ilaria
Published: March 2023

Effective school-based mental health programs are a research field with growing interest and great social value. At the stage of development and initial testing of the program, as well as during dissemination, and adaptation in other cultures, it is important that the implementation is carried out in the way that was originally intended. Fidelity or adherence is the most often used concept relating to the extent to which the implemented intervention corresponds to the originally intended program. Therefore, monitoring of the implementation is an essential element necessary to integrate into contemporary evidence-based program. The current paper describes the monitoring system developed for the Promoting Mental Health at Schools (PROMEHS) project. The monitoring was done on both the structural and procedural aspects of the program’s implementation, involving the evaluation of five core aspects: fidelity, dosage, quality, responsiveness, and adaptation. This methods article aims to describe the development of the monitoring system and to analyze the strengths of the qualitative-quantitative multi-informant approach in the monitoring of the intervention’s implementation. In the future, this would support further research on effectiveness of the PROMEHS program.
Development and validation of the caregiver needs and resources assessment
Authors: Li Kin-Kit , Leung Cyrus L. K. , Yeung Dannii , Chiu Marcus Y. L. , Chong Alice M. L. , Lam Beck C. Y. , Chung Edwin K. H. , Lo T. Wing
Published: March 2023

Introduction

Existing caregiver assessment tools were long criticized for focusing on the needs and burden while neglecting the importance of the resources. The current study aimed to develop a multidimensional and time-effective assessment tool that measures both needs and resources of non-paid family caregivers of older adults for screening and service-matching purposes.

Methods

Items of the Caregiver Needs and Resources Assessment (CNRA) were developed from extensive literature reviews and focus group interviews of family caregivers and social workers in the field. In addition, we collected 317 valid responses from family caregivers of older adults from local non-government organizations in examining the psychometric properties of the CNRA.

Results

The results revealed a 12-factor structure that fitted nicely into the conceptual frame of needs and resources domains. Need factors were positively associated with mental health symptoms, while resource factors were positively associated with peace in mind, meaning-making, and personal gain measures. The 36-item CNRA revealed good internal reliability and convergent validity.

Discussion

The CNRA has the potential to be used as a compact yet balanced assessment tool for understanding both the needs and resources of caregivers for human service professionals.
Empowering leadership during the COVID-19 outbreak: Implications for work satisfaction and effectiveness in organizational teams
Authors: Cremers Erik Eduard , Curşeu Petru Lucian
Published: March 2023

The COVID-19 pandemic generated unprecedented challenges for social and organizational life. We set out to explore how empowering leadership and leadership support were affected as a result of the team-based organization starting to implement flexible and remote work practices after the outbreak of the COVID-19 pandemic. We collected data in a cross-lagged design and used the two-condition MEMORE mediation procedure to analyze data on work satisfaction and team effectiveness obtained just before and immediately after the COVID-19 outbreak in 34 organizational teams. Our results show that the COVID-19 outbreak did not significantly impact perceptions of empowering leadership or perceived leadership support. However, teams that experienced changes in empowering leadership also reported proportional changes in work satisfaction and effectiveness. Finally, we show that the association between empowering leadership and leadership support, on the one hand, and work satisfaction in teams, on the other hand, is moderated by team size, such that the strength of the association is higher in small rather than large organizational teams. We conclude by arguing that the team-based organization absorbed well the impact and disruptions associated with the COVID-19 outbreak. We also stress the role of empowering leadership as a driver of work satisfaction and the effectiveness of organizational teams.
Consumers' body image expressions: Reflection of a Snow White or an Evil Queen
Authors: Wagner Ralf , Singh Swati
Published: March 2023

Introduction

The aim of this paper is to explore how minimal-self impacts the body image, projecting it as a reflection of one's approach toward their health and mental well-being.

Methods

The study takes qualitative data from two countries India and Germany and draws on a qualitative study of 20 individuals who are involved in some kind of physical activity for a long time. This paper examines the body image perspectives from Grimms Brothers fairytale characters showcasing fit and healthy perspectives on Snow White side and projected and superfluous perspectives on Evil Queen side. The study also provides a model deciphering the rationale for both the reflections.

Results

The body image projection from Snow White perspectives (success & dedication, self-esteem, bodybuilding, and cosmetic surgery) relates to positive reflection of oneself with focus on fitness, discipline, and mental rejuvenation in life. Notably, Evil Queen perspectives (unrealistic makeover, dark side of social media, gain an edge over others, and mental benchmarking with fair skin) reveal these facets as motivators to equip their body as means of physical non-verbal communication assets.

Conclusion

Analysis shows that there is no clear white or black view of health and fitness projection via body image but it's a gray line that gives wholesome fitness either a holistic mental peace or a competitive or success-oriented approach.
Cognitive–behavioral factors in tinnitus-related insomnia
Authors: Barry Gemma , Marks Elizabeth
Published: March 2023

Background

A significant proportion of individuals with distressing tinnitus also report insomnia. Limited, but emerging, evidence suggests that tinnitus-related insomnia cannot be explained only by the presence of tinnitus and that sleep-related cognitive–behavioral processes may play a key role in exacerbating tinnitus-related insomnia.

Objectives

This study aimed to assess whether sleep-related cognitions and behaviors believed to maintain insomnia disorder are present in individuals with tinnitus-related insomnia.

Methods

This between-groups study recruited 180 participants online for four groups: tinnitus-related insomnia (N = 49), insomnia disorder without tinnitus (N = 34), tinnitus sufferers who are good sleepers (N = 38), and controls (N = 59). They completed questionnaires assessing insomnia severity, sleep-related cognitions and behaviors, sleep quality, anxiety, and depression. People with tinnitus completed a measure of tinnitus severity and rated the loudness of their tinnitus on a subjective measure.

Results

Linear regression demonstrated that group significantly predicted sleep related thoughts and behaviors, and sleep quality. Pairwise comparisons showed that the tinnitus-related insomnia group had significantly greater insomnia-related thoughts and behaviors and significantly worse sleep quality than tinnitus-good sleepers. No differences were seen between the tinnitus-related insomnia and the insomnia groups. The tinnitus-related insomnia group had significantly higher depression, anxiety, and tinnitus distress than tinnitus-good sleepers.

Conclusion

Findings suggest that tinnitus-related insomnia may be maintained by cognitive–behavioral processes similar to those found in insomnia disorder. Such processes are more important than tinnitus severity when understanding sleep disturbance. People with tinnitus-related insomnia may benefit from treatments such as cognitive–behavioral therapy for insomnia.