bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping Internal Knowledge Transfers in Multinational Corporations
Authors: Castro Rita , Moreira António Carrizo
Published: January 2023

Managing multiple knowledge transfers between headquarters and subsidiaries, among subsidiaries, and also within each of these units is crucial for multinational corporations’ (MNCs) survival. Therefore, this article aims to uncover the main factors influencing internal knowledge transfers in MNCs—including intra-unit knowledge transfers and transfers between units, namely, conventional, horizontal, and reverse knowledge transfers. To achieve this goal, a systematic literature review (SLR) was conducted to synthesize the content of 85 articles. From a set of 1439 papers, only 85 related to knowledge transfer and knowledge sharing were considered. Based on an inductive thematic approach, eight different research categories and 97 topics were identified. Four different internal knowledge transfers (intra knowledge transfer (IKT), horizontal knowledge transfer (HKT), conventional knowledge transfer (CKT), and reverse knowledge transfer (RKT)) are compared across eight thematic categories and 97 topics. According to the results obtained, the depth of the topics analyzed varies, as does the variety of categories, with RKT being more deeply analyzed than IKT. There is a clear dominance of vertical knowledge transfer (CKT + RHT) over HKT. The exercise of power (e.g., size, knowledge base) still dominates CKT and RKT in most of the studies analyzed, which are traditionally affected by the characteristics of MNCs, HQs and subsidiaries. The debate on HKT is affected by the classical perspectives of power-based relations (e.g., expatriates, size, knowledge base) among subsidiaries. Although important, intra-unit knowledge transfer is greatly influenced by characteristics.
Agrochemicals—The Pesticides Section
Authors: Athanassiou Christos G.
Published: January 2023

The journal Agrochemicals publishes research on the different types of agrochemicals, as depicted in this Editorial [...]
Oxyfluorfen and Linuron: Residual Effect of Pre-Emergence Herbicides in Three Tropical Soils
Authors: Paula Dilma F. de , Ferreira Guilherme A. de P. , Guimarães Tiago , Brochado Maura G. da S. , Hahn Leandro , Mendes Kassio F.
Published: January 2023

Knowledge about the residual effect of herbicides is important in order to increase agronomic efficacy and reduce environmental problems. Therefore, the objective of this study was to evaluate the residual effect of oxyfluorfen and linuron in three soils. Pots of 0.35 dm3 were filled with three Brazilian soils: Ultisol, Oxisol, and Inceptisol. Then, the herbicides were applied at different times at 0, 15, 30, 45, 60, 90, 120, 150, 180, and 200 days and the bioindicator species of linuron and oxyfluorfen were sown. Then, the injury was evaluated at 7, 14, and 21 days after emergence (DAE) to find the half-life of the herbicide residue level (RL50) and the dose of herbicide that provides a 50% reduction in dry matter (GR50). In the soil with oxyfluorfen application, the RL50 at 21 DAE was 59, 57, and 51 days and GR50 was 49, 47, and 31 days for Ultisol, Oxisol, and Inceptisol, respectively. Soils with linuron application had RL50 of 75, 92, and 149 days and GR50 of 52, 48, and 120 days for Ultisol, Oxisol, and Inceptisol, respectively. The higher organic matter and clay content of Ultisol compared to Oxisol and Inceptisol resulted in a lower residual effect of linuron. There was little difference between soil type and the residual effect of oxyfluorfen, which may be related to the physicochemical characteristics of the molecule.
Effect of the Addition of Humic Substances on Morphometric Analysis and Number of Goblet Cells in the Intestinal Mucosa of Broiler Chickens
Authors: López-García Yair Román , Gómez-Rosales Sergio , Angeles María de Lourdes , Jiménez-Severiano Héctor , Merino-Guzman Rubén , Téllez-Isaias Guillermo
Published: January 2023

The mechanisms of action of humic substances (HS) as growth promoters in poultry are unknown. In this study, the productive performance, histology, and number of goblet cells (GC) in the intestinal villi of broilers under steady-state digestive conditions and under abrupt changes in diet with the addition of HS was evaluated. Broilers housed individually were offered three treatments from 14–28 days: 1 = diet with white corn/soybean meal, without growth promoter antibiotics (nonGPA); 2 = with GPA (GPA); and 3 = with 0.3% HS. At day 28, two diets were suddenly introduced: (A) white corn/soybean meal plus dried distillers’ grains with solubles (DDGS); and (B) white/blue corn/soybean meal/DDGS, keeping the three original treatments. Diets A and B were also exchanged on day 37. FCR was lower with GPA and HS compared to nonGPA from 14–38 days (p < 0.05); at day 28, under steady-state digestive conditions, HS had a similar effect to GPA on the histology and GC number in the jejunum villi. The number of GC in the jejunum of HS-fed broilers on days 29 and 38, after diet changes, behaves similarly to that of AGP-fed broilers (p > 0.05). HS appears to strengthen the mucosal protection of the epithelium of the intestine.
Effects of High-Intensity Laser Therapy (HILT) on Skin Surface Temperature and Vein Diameter in Healthy Racehorses with Clipped and Non-Clipped Coat
Authors: Zielińska Paulina , Soroko-Dubrovina Maria , Śniegucka Karolina , Dudek Krzysztof , Čebulj-Kadunc Nina
Published: January 2023

The aim of this study was to investigate the differences in the effects of high-intensity laser therapy (HILT) on skin surface temperature and vein diameter in the carpal joint region in racehorses with clipped and non-clipped treatment areas. The study included 20 Thoroughbreds split into two equal groups: clipped coat and non-clipped coat. Horses underwent thermographic examination to detect changes in skin surface temperature at the medial surface of the carpal joint, followed by ultrasonographic examination to assess changes in the diameter of the medial palmar vein before and after HILT. The increase in skin surface temperature after HILT was significantly lower in the group with clipped coat than in the non-clipped group. The group with clipped coat showed a greater increase in vessel diameter. There was a significantly weak negative correlation between the changes in average skin surface temperature and vein diameter in both groups. In conclusion, an efficient photothermal effect can be achieved in skin with a non-clipped coat and clipping the treatment area increases photobiostimulation of the tissue, while reducing the photothermal effect. Further research is needed to specify the parameters for the treatment of skin with clipped and non-clipped coat in order to perform effective laser therapy.
The Evanescent Bouquet of Individual Bear Fingerprint
Authors: Mazzatenta Andrea , Fiorito Serena , Guadagnini Roberto , Genovese Salvatore , Valentini Alberto , Bonadiman Federica , Guadagnini Sofia , Epifano Francesco , Mollica Adriano
Published: January 2023

The evanescent and invisible communication carried by chemical signals, pheromones, or signature mixtures or, as we prefer, the pheromonal individual fingerprint, between members of the same species is poorly studied in mammals, mainly because of the lack of identification of the molecules. The difference between pheromones and the pheromonal individual fingerprint is that the former generate stereotyped innate responses while the latter requires learning, i.e., different receivers can learn different signature mixtures from the same individual. Furthermore, pheromones are usually produced by a particular gland, while the pheromonal individual fingerprint is the entire bouquet produced by the entire secreting gland of the body. In the present study, we aim to investigate the pheromonal individual fingerprint of brown bears in northern Italy. We collected the entire putative pheromone bouquet from all production sites in free-ranging bears and analyzed the entire crude extract to profile the individual fingerprint according to species-, sex- and subjective-specific characteristics. We were able to putatively characterize the brown bears’ pheromonal individual fingerprints and compare them with the partial pheromone identifications published by other studies. This work is a step forward in the study of the complexity of chemical communication, particularly in a solitary endangered species.
Tend and Befriend in Horses: Partner Preferences, Lateralization, and Contextualization of Allogrooming in Two Socially Stable Herds of Quarter Horse Mares
Authors: Kieson Emily , Goma Amira A. , Radi Medhat
Published: January 2023

Studies show that horses express favoritism through shared proximity and time and demonstrate unique affiliative behaviors such as allogrooming (mutual scratching) with favorite conspecifics. Allogrooming also occurs more frequently during stress and has been observed to occur more frequently in domestic herds than feral. The role of partner preference, lateralization, and duration of allogrooming as measures of social bonding has remained unclear. The present study looked at two socially stable herds of mares (n = 85, n = 115) to determine the frequency, duration, visual field of view and partner preference during allogrooming in both pasture settings (low stress) and confined settings (higher stress). One hundred and fifty-three videos for both herds were coded for allogrooming behaviors with 6.86 h recorded in confined conditions and 31.9 h in pasture settings. Six allogrooming sessions were observed in the pasture setting with an average duration of 163.11 s. In confined settings, a total of 118 allogrooming sessions were observed with an average duration of 40.98 s. Significant (p < 0.01) differences were found between settings for duration (s), number of allogrooming pairs, and frequency of allogrooming (per min) for each herd. All observed allogrooming sessions involved pairs of favored conspecifics (one partner per horse). The current study suggests that horses may have friendships that can be observed through the demonstration of specific affiliative behaviors during times of stress with more frequent, but shorter affiliative interactions with preferred partners during times of stress. This context suggests that horses adhere to the “tend and befriend” principles of friendship in animals.
A New AS-PCR Method to Detect CSN201 Allele, Genotyping at Ca-Sensitive Caseins Loci and Milk Traits Association Studies in Autochthonous Lazio Goats
Authors: Cosenza Gianfranco , Albarella Sara , D’Anza Emanuele , Iannuzzi Alessandra , Selvaggi Maria , Pugliano Mariagiulia , Galli Tiziana , Saralli Giorgio , Ciotola Francesca , Peretti Vincenzo
Published: January 2023

Calcium-sensitive caseins are the main protein component of milk. In the goat, they are encoded by three genes (CSN1S1, CSN2, and CSN1S2) located on chromosome 6. A high number of alleles has been discovered for these genes in the goat species, responsible for changes in the milk’s qualitative and quantitative characteristics. This study aimed to develop an Allele-Specific PCR (AS-PCR), which allowed us to unequivocally detect goat carriers of the CSN201 allele. Subsequently, the calcium-sensitive casein loci genotype was investigated in three native goat breeds of the Lazio Region (Bianca Monticellana, Capestrina, and Ciociara Grigia). No individuals were carriers of the CSN1S101, CSN1S1E, CSN201, CSN1S2D, and CSN1S20 alleles, while a high frequency of the alleles CSN1S1F and CSN1S1A*,B* was observed. Association analyses between the different genotypes at the CSN1S1 locus and some milk traits, namely the fat and protein yielded and the fat, protein, solids-not-fat, and casein percentages without an effect on the milk yield, were observed.
Airway Smooth Muscle Regulated by Oxidative Stress in COPD
Authors: Kume Hiroaki , Yamada Ryuki , Sato Yuki , Togawa Ryuichi
Published: January 2023

Since COPD is a heterogeneous disease, a specific anti-inflammatory therapy for this disease has not been established yet. Oxidative stress is recognized as a major predisposing factor to COPD related inflammatory responses, resulting in pathological features of small airway fibrosis and emphysema. However, little is known about effects of oxidative stress on airway smooth muscle. Cigarette smoke increases intracellular Ca2+ concentration and enhances response to muscarinic agonists in human airway smooth muscle. Cigarette smoke also enhances proliferation of these cells with altered mitochondrial protein. Hydrogen peroxide and 8-isoprostans are increased in the exhaled breath condensate in COPD. These endogenous oxidants cause contraction of tracheal smooth muscle with Ca2+ dynamics through Ca2+ channels and with Ca2+ sensitization through Rho-kinase. TNF-α and growth factors potentiate proliferation of these cells by synthesis of ROS. Oxidative stress can alter the function of airway smooth muscle through Ca2+ signaling. These phenotype changes are associated with manifestations (dyspnea, wheezing) and pathophysiology (airflow limitation, airway remodeling, airway hyperresponsiveness). Therefore, airway smooth muscle is a therapeutic target against COPD; oxidative stress should be included in treatable traits for COPD to advance precision medicine. Research into Ca2+ signaling related to ROS may contribute to the development of a novel agent for COPD.
Early Warning Signals of Dry-Wet Transition Based on the Critical Slowing Down Theory: An Application in the Two-Lake Region of China
Authors: Wu Hao , Yan Pengcheng , Hou Wei , Wang Jinsong , Zuo Dongdong
Published: January 2023

In recent years, the dry-wet transition (DWT), which often leads to regional floods and droughts, has become increasingly frequent in the Poyang Lake basin and the Dongting Lake basin (hereinafter referred to as the two-lake region). This study aims to investigate the early warning signals (EWSs) for DWT events. Firstly, based on the standardized precipitation index (SPI) at 161 meteorological stations in the two-lake region from 1961 to 2020, the two-lake region is divided into four sub-regions by the Rotational Empirical Orthogonal Function (REOF) analysis method. Then, the occurrence time of the DWT events in each sub-region is determined by the moving t-test (MTT) technique. Finally, by using two indicators (variance and the auto-correlation coefficient) to describe the critical slowing down (CSD) phenomenon, the EWSs denoting the DWT events in all sub-regions are investigated. The results reveal that there was a significant dry-to-wet (wet-to-dry) event around 1993 (2003) in the two-lake region during the last 60 years. The phenomenon of CSD, where the auto-correlation coefficient and variance increases are found in all sub-regions around 10 years before the DWT, suggests that it can be taken as an EWS for the DWT events. This study confirms the effectiveness of applying the slowing down theory in investigating the EWSs for abrupt changes in the two-lake region, aiming to provide a theoretical basis for effective prevention and mitigation against disasters in this region. Moreover, it is expected to be well-applied to the middle and lower reaches of the Yangtze River.
Fixed Point Theorems for Generalized Classes of Operators
Authors: Ionescu Cristiana
Published: January 2023

In this work, we consider weakly generalized operators, which extend the Geraghty mappings that are studied with regard to the existence and uniqueness of their fixed points, in the setting offered by strong b-metric spaces. Classic results are obtained as corollaries. An example is provided to support these outcomes.
Regulation of EWSR1-FLI1 Function by Post-Transcriptional and Post-Translational Modifications
Authors: Yu Le , Davis Ian J. , Liu Pengda
Published: January 2023

Ewing sarcoma is the second most common bone tumor in childhood and adolescence. Currently, first-line therapy includes multidrug chemotherapy with surgery and/or radiation. Although most patients initially respond to chemotherapy, recurrent tumors become treatment refractory. Pathologically, Ewing sarcoma consists of small round basophilic cells with prominent nuclei marked by expression of surface protein CD99. Genetically, Ewing sarcoma is driven by a fusion oncoprotein that results from one of a small number of chromosomal translocations composed of a FET gene and a gene encoding an ETS family transcription factor, with ~85% of tumors expressing the EWSR1::FLI1 fusion. EWSR1::FLI1 regulates transcription, splicing, genome instability and other cellular functions. Although a tumor-specific target, EWSR1::FLI1-targeted therapy has yet to be developed, largely due to insufficient understanding of EWSR1::FLI1 upstream and downstream signaling, and the challenges in targeting transcription factors with small molecules. In this review, we summarize the contemporary molecular understanding of Ewing sarcoma, and the post-transcriptional and post-translational regulatory mechanisms that control EWSR1::FLI1 function.
New Frontiers in Colorectal Cancer Treatment Combining Nanotechnology with Photo- and Radiotherapy
Authors: Freitas Sara C. , Sanderson Daniel , Caspani Sofia , Magalhães Ricardo , Cortés-Llanos Belén , Granja Andreia , Reis Salette , Belo João Horta , Azevedo José , Gómez-Gaviro Maria Victoria , Sousa Célia Tavares de
Published: January 2023

Colorectal cancer is the third most common cancer worldwide. Despite recent advances in the treatment of this pathology, which include a personalized approach using radio- and chemotherapies in combination with advanced surgical techniques, it is imperative to enhance the performance of these treatments and decrease their detrimental side effects on patients’ health. Nanomedicine is likely the pathway towards solving this challenge by enhancing both the therapeutic and diagnostic capabilities. In particular, plasmonic nanoparticles show remarkable potential due to their dual therapeutic functionalities as photothermal therapy agents and as radiosensitizers in radiotherapy. Their dual functionality, high biocompatibility, easy functionalization, and targeting capabilities make them potential agents for inducing efficient cancer cell death with minimal side effects. This review aims to identify the main challenges in the diagnosis and treatment of colorectal cancer. The heterogeneous nature of this cancer is also discussed from a single-cell point of view. The most relevant works in photo- and radiotherapy using nanotechnology-based therapies for colorectal cancer are addressed, ranging from in vitro studies (2D and 3D cell cultures) to in vivo studies and clinical trials. Although the results using nanoparticles as a photo- and radiosensitizers in photo- and radiotherapy are promising, preliminary studies showed that the possibility of combining both therapies must be explored to improve the treatment efficiency.
Roles of IL-7R Induced by Interactions between Cancer Cells and Macrophages in the Progression of Esophageal Squamous Cell Carcinoma
Authors: Kitamura Yu , Koma Yu-ichiro , Tanigawa Kohei , Tsukamoto Shuichi , Azumi Yuki , Miyako Shoji , Urakami Satoshi , Kodama Takayuki , Nishio Mari , Shigeoka Manabu , Kakeji Yoshihiro , Yokozaki Hiroshi
Published: January 2023

High infiltration of tumor-associated macrophages (TAMs), which contribute to the progression of several cancer types, is correlated with poor prognosis of esophageal squamous cell carcinoma (ESCC). In addition to the previously reported increase in migration and invasion, ESCC cells co-cultured directly with macrophages exhibited enhanced survival and growth. Furthermore, interleukin-related molecules are associated with ESCC; however, the precise mechanism underlying this association is unclear. Therefore, we explored the role of interleukin-related molecules in ESCC progression. A cDNA microarray analysis of monocultured and co-cultured ESCC cells revealed that the interleukin 7 receptor (IL-7R) was upregulated in ESCC cells co-cultured with macrophages. Overexpression of IL-7R promoted the survival and growth of ESCC cells by activating the Akt and Erk1/2 signaling pathways. The IL-7/IL-7R axis also contributed to the promotion of ESCC cell migration via the Akt and Erk1/2 signaling pathways. Furthermore, immunohistochemistry showed that ESCC patients with high IL-7R expression in cancer nests exhibited a trend toward poor prognosis in terms of disease-free survival, and showed significant correlation with increased numbers of infiltrating macrophages and cancer-associated fibroblasts. Therefore, IL-7R, which is upregulated when directly co-cultured with macrophages, may contribute to ESCC progression by promoting the development of various malignant phenotypes in cancer cells.
A Phase II, Open-Label Clinical Trial of Intranasal Ketamine for Depression in Patients with Cancer Receiving Palliative Care (INKeD-PC Study)
Authors: Rosenblat Joshua D. , deVries Froukje E. , Doyle Zoe , McIntyre Roger S. , Rodin Gary , Zimmermann Camilla , Mak Ernie , Hannon Breffni , Schulz-Quach Christian , Kindy Aida Al , Patel Zeal , Li Madeline
Published: January 2023

Antidepressants require several weeks for the onset of action, a lag time that may exceed life expectancy in palliative care. Ketamine has demonstrated rapid antidepressant effects, but has been minimally studied in cancer and palliative care populations. Herein, the objective was to determine the feasibility, safety, tolerability and preliminary efficacy of intranasal racemic ketamine for major depressive disorder (MDD) in patients with advanced cancer. We conducted a single-arm, open-label phase II trial at the Princess Margaret Cancer Centre in Toronto, ON, Canada. Participants with advanced cancer with moderate to severe MDD received three flexible doses of intranasal (IN) ketamine (50–150 mg) over a one-week period. The primary efficacy outcome was an antidepressant response and remission rates as determined by the Montgomery–Åsberg Depression Rating Scale (MADRS) from baseline to the Day 8 primary endpoint. Twenty participants were enrolled in the trial, receiving at least one dose of IN ketamine, with fifteen participants receiving all three doses. The Day 8 antidepressant response (MADRS decreased by >50%) and remission (MADRS < 10 on Day 8) rates were high at 70% and 45%, respectively. Mean MADRS scores decreased significantly from baseline (mean MADRS of 31, standard deviation 7.6) to Day 8 (11 +/− 7.4) with an overall decrease of 20 points (p < 0.001). Antidepressant effects were partially sustained in the second week in the absence of additional ketamine doses, with a Day 14 mean MADRS score of 14 +/− 9.9. Common adverse effects included fatigue, dissociation, nausea, dysgeusia and headaches; almost all adverse effects were mild and transient, resolving within 2 h of each ketamine dose with one dropout related to adverse effects (negative dissociative episode). Given these promising findings, larger, controlled trials are merited.
Role of Clock Genes and Circadian Rhythm in Renal Cell Carcinoma: Recent Evidence and Therapeutic Consequences
Authors: Santoni Matteo , Molina-Cerrillo Javier , Santoni Giorgio , Lam Elaine T. , Massari Francesco , Mollica Veronica , Mazzaschi Giulia , Rapoport Bernardo L. , Grande Enrique , Buti Sebastiano
Published: January 2023

Circadian rhythm regulates cellular differentiation and physiology and shapes the immune response. Altered expression of clock genes might lead to the onset of common malignant cancers, including Renal Cell Carcinoma (RCC). Data from Cancer Genome Atlas (TCGA) indicate that clock genes PER1-3, CRY2, CLOCK, NR1D2 and RORα are overexpressed in RCC tissues and correlate with patients’ prognosis. The expression of clock genes could finely tune transcription factor activity in RCC and is associated with the extent of immune cell infiltration. The clock system interacts with hypoxia-induced factor-1α (HIF-1α) and regulates the circadian oscillation of mammalian target of rapamycin (mTOR) activity thereby conditioning the antitumor effect of mTOR inhibitors. The stimulation of natural killer (NK) cell activity exerted by the administration of interferon-α, a cornerstone of the first era of immunotherapy for RCC, relevantly varies according to circadian dosing time. Recent evidence demonstrated that time-of-day infusion directly affects the efficacy of immune checkpoint inhibitors in cancer patients. Compounds targeting the circadian clock have been identified and their role in the era of immunotherapy deserves to be further investigated. In this review, we aimed at addressing the impact of clock genes on the natural history of kidney cancer and their potential therapeutic implications.
VATS versus Open Lobectomy following Induction Therapy for Stage III NSCLC: A Propensity Score-Matched Analysis
Authors: Hireche Kheira , Lounes Youcef , Bacri Christophe , Solovei Laurence , Marty-Ané Charles , Canaud Ludovic , Alric Pierre
Published: January 2023

Objectives: This study aims to evaluate the perioperative and oncologic outcomes of thoracoscopic lobectomy for advanced stage III NSCLC. Methods: We retrospectively reviewed 205 consecutive patients who underwent VATS or open lobectomy for clinical stage III lung cancer between January 2013 and December 2020. The perioperative and oncologic outcomes of the two approaches were compared. Long-term survival was assessed using the Kaplan–Meier estimator. Propensity score-matched (PSM) comparisons were used to obtain a well-balanced cohort of patients undergoing VATS and open lobectomy. Results: VATS lobectomy was performed in 77 (37.6%) patients and open lobectomy in 128 (62.4%) patients. Twelve patients (15.6%) converted from VATS to the open approach. PSM resulted in 64 cases in each group, which were well matched according to twelve potential prognostic factors, including tumor size, histology, and pTNM stage. Between the VATS and the open group, there were no significant differences in unmatched and matched analyses, respectively, of the overall postoperative complications (p = 0.138 vs. p = 0.109), chest tube duration (p = 0.311 vs. p = 0.106), or 30-day mortality (p = 1 vs. p = 1). However, VATS was associated with shorter hospital stays (p < 0.0001). The five-year overall survival (OS) and five-year Recurrence-free survival (RFS) were comparable between the VATS and the open groups. There was no significant difference in the recurrence pattern between the two groups in both the unmatched and matched analyses. Conclusion: For the advanced stage III NSCLC, VATS lobectomy achieved equivalent postoperative and oncologic outcomes when compared with open lobectomy without increasing the risk of procedure-related locoregional recurrence.
The Contribution of Germline Pathogenic Variants in Breast Cancer Genes to Contralateral Breast Cancer Risk in BRCA1/BRCA2/PALB2-Negative Women
Authors: Larionov Alexey , Fewings Eleanor , Redman James , Goldgraben Mae , Clark Graeme , Boice John , Concannon Patrick , Bernstein Jonine , Conti David V. ,   the WECARE Study Collaborative Group, Tischkowitz Marc
Published: January 2023

Background: Contralateral breast cancer (CBC) is associated with younger age at first diagnosis, family history and pathogenic germline variants (PGVs) in genes such as BRCA1, BRCA2 and PALB2. However, data regarding genetic factors predisposing to CBC among younger women who are BRCA1/2/PALB2-negative remain limited. Methods: In this nested case-control study, participants negative for BRCA1/2/PALB2 PGVs were selected from the WECARE Study. The burden of PGVs in established breast cancer risk genes was compared in 357 cases with CBC and 366 matched controls with unilateral breast cancer (UBC). The samples were sequenced in two phases. Whole exome sequencing was used in Group 1, 162 CBC and 172 UBC (mean age at diagnosis: 42 years). A targeted panel of genes was used in Group 2, 195 CBC and 194 UBC (mean age at diagnosis: 50 years). Comparisons of PGVs burdens between CBC and UBC were made in these groups, and additional stratified sub-analysis was performed within each group according to the age at diagnosis and the time from first breast cancer (BC). Results: The PGVs burden in Group 1 was significantly higher in CBC than in UBC (p = 0.002, OR = 2.5, 95CI: 1.2–5.6), driven mainly by variants in CHEK2 and ATM. The proportions of PGVs carriers in CBC and UBC in this group were 14.8% and 5.8%, respectively. There was no significant difference in PGVs burden between CBC and UBC in Group 2 (p = 0.4, OR = 1.4, 95CI: 0.7–2.8), with proportions of carriers being 8.7% and 8.2%, respectively. There was a significant association of PGVs in CBC with younger age. Metanalysis combining both groups confirmed the significant association between the burden of PGVs and the risk of CBC (p = 0.006) with the significance driven by the younger cases (Group 1). Conclusion: In younger BRCA1/BRCA2/PALB2-negative women, the aggregated burden of PGVs in breast cancer risk genes was associated with the increased risk of CBC and was inversely proportional to the age at onset.
Laparoscopic Repeat Liver Resection—Selecting the Best Approach for Repeat Liver Resection
Authors: Morise Zenichi , Katsuno Hidetoshi , Kikuchi Kenji , Endo Tomoyoshi , Matsuo Kazuhiro , Asano Yukio , Horiguchi Akihiko
Published: January 2023

Recurrence of liver cancers after liver resection (LR), such as recurrences of hepatocellular carcinoma and colorectal liver metastases, is often treated with repeat LR (RLR) as the only curative treatment. However, RLR is associated with an increased risk of complications. The indications for the currently emerging laparoscopic LR and its advantages and disadvantages for repeat treatment are still under discussion. Our multi-institutional propensity-score matched analyses of laparoscopic vs. open RLRs for hepatocellular carcinoma showed the feasibility of laparoscopic RLR with comparable short- and long-term outcomes. Small blood loss and low morbidity was observed in selected patients treated using laparoscopic RLR in which total adhesiolysis can be dodged, with speculations that laparoscopic minor repeated LR can minimize functional deterioration of the liver. However, there are several disadvantages, such as easily occurring disorientation and difficulty in repeated wide-range dissection of Glissonian pedicles. Recently emerging small anatomical resection, indocyanine green fluorescence-guided surgery, and robot-assisted surgery are promising tools for the further development of laparoscopic RLR. This review discusses how laparoscopic RLR, as a powerful unique local therapy causing less damage to the residual liver and surrounding structures, could contribute to the outcomes of repeated treatments for cancers and its future perspectives.
Feasibility of Using Wearables for Home Monitoring during Radiotherapy for Head and Neck Cancer—Results from the OncoWatch 1.0 Study
Authors: Holländer-Mieritz Cecilie , Steen-Olsen Emma Balch , Kristensen Claus Andrup , Johansen Christoffer , Vogelius Ivan Richter , Pappot Helle
Published: January 2023

Background: Consumer wearables allow objective health data monitoring, e.g., of physical activity and heart rate, which might change over a cancer treatment course. Patients with head and neck cancer (HNC) receiving radiotherapy (RT) with curative intent typically experience side effects such as pain, decreased appetite, and dehydration, which may lead to hospitalizations. Therefore, health data monitoring could be important to understand a patient’s condition outside the hospital. The OncoWatch 1.0 study investigated the feasibility of using smartwatches for patients with HNC receiving RT. Methods: This study was a prospective, single-cohort feasibility study. The inclusion criteria were patients ≥ 18 years of age who planned to receive curatively intended radiotherapy for HNC. Consenting patients were asked to wear a smartwatch during RT and until two weeks after the end of RT. The primary endpoint was adherence. The secondary endpoints were data acquisition and variations in heart rate and physical activity. Results: Ten patients were included, with a median age of 62 years and eight males. The adherence rate for wearing the watch >12 h/d over the study period was 31%. The data acquisition rate was 61%. Conclusions: Although the primary endpoint was not reached, new knowledge has been established, including the secure data setup and key points that need to be addressed in future studies.
Tight Junction Protein Signaling and Cancer Biology
Authors: Nehme Zeina , Roehlen Natascha , Dhawan Punita , Baumert Thomas F.
Published: January 2023

Tight junctions (TJs) are intercellular protein complexes that preserve tissue homeostasis and integrity through the control of paracellular permeability and cell polarity. Recent findings have revealed the functional role of TJ proteins outside TJs and beyond their classical cellular functions as selective gatekeepers. This is illustrated by the dysregulation in TJ protein expression levels in response to external and intracellular stimuli, notably during tumorigenesis. A large body of knowledge has uncovered the well-established functional role of TJ proteins in cancer pathogenesis. Mechanistically, TJ proteins act as bidirectional signaling hubs that connect the extracellular compartment to the intracellular compartment. By modulating key signaling pathways, TJ proteins are crucial players in the regulation of cell proliferation, migration, and differentiation, all of which being essential cancer hallmarks crucial for tumor growth and metastasis. TJ proteins also promote the acquisition of stem cell phenotypes in cancer cells. These findings highlight their contribution to carcinogenesis and therapeutic resistance. Moreover, recent preclinical and clinical studies have used TJ proteins as therapeutic targets or prognostic markers. This review summarizes the functional role of TJ proteins in cancer biology and their impact for novel strategies to prevent and treat cancer.
The Effects of Combined Exposure to Simulated Microgravity, Ionizing Radiation, and Cortisol on the In Vitro Wound Healing Process
Authors: Radstake Wilhelmina E. , Gautam Kiran , Miranda Silvana , Vermeesen Randy , Tabury Kevin , Rehnberg Emil , Buset Jasmine , Janssen Ann , Leysen Liselotte , Neefs Mieke , Verslegers Mieke , Claesen Jürgen , van Goethem Marc-Jan , Weber Uli , Fournier Claudia , Parisi Alessio , Brandenburg Sytze , Durante Marco , Baselet Bjorn , Baatout Sarah
Published: January 2023

Human spaceflight is associated with several health-related issues as a result of long-term exposure to microgravity, ionizing radiation, and higher levels of psychological stress. Frequent reported skin problems in space include rashes, itches, and a delayed wound healing. Access to space is restricted by financial and logistical issues; as a consequence, experimental sample sizes are often small, which limits the generalization of the results. Earth-based simulation models can be used to investigate cellular responses as a result of exposure to certain spaceflight stressors. Here, we describe the development of an in vitro model of the simulated spaceflight environment, which we used to investigate the combined effect of simulated microgravity using the random positioning machine (RPM), ionizing radiation, and stress hormones on the wound-healing capacity of human dermal fibroblasts. Fibroblasts were exposed to cortisol, after which they were irradiated with different radiation qualities (including X-rays, protons, carbon ions, and iron ions) followed by exposure to simulated microgravity using a random positioning machine (RPM). Data related to the inflammatory, proliferation, and remodeling phase of wound healing has been collected. Results show that spaceflight stressors can interfere with the wound healing process at any phase. Moreover, several interactions between the different spaceflight stressors were found. This highlights the complexity that needs to be taken into account when studying the effect of spaceflight stressors on certain biological processes and for the aim of countermeasures development.
Public Health Impact and Health System Preparedness within a Changing Climate in Bangladesh: A Scoping Review
Authors: Nahian Mahin Al
Published: January 2023

Bangladesh, one of the most disaster-prone countries in the world is also severely exposed to climate change (CC) impacts with a multitude of health complexities. Health adaptation to CC is thus a serious issue in Bangladesh, but not explored properly from a health system and policy environment perspective. In order to address this gap and provide a holistic picture of the overall scenario, this scoping review explores CC impacts on the population health in Bangladesh and discusses the policy environment and health system preparedness against such climatic challenges. A total of 28 articles were reviewed following Arksey and O’Malley’s scoping review framework. A “5-point scale” was devised to assess CC integration in the health sector Operational Plans (OPs). Though the country made significant progress in different health indicators, poverty and income inequality have kept marginal communities out of many health provisions. There are four major stakeholders in the health system. The government sector is handicapped by poor governance, bureaucratic processes, and staff shortages; and primarily focuses on the public sector only. National Health Policy (NHP) governs the health system through 29 sectoral OPs, that put CC as a major cross-cutting issue. About 25% of the OPs have fully integrated CC and other OPs have significant CC co-benefits. In Bangladesh CC was linked to increased morbidity and mortality, diarrhea, cholera, skin problems, respiratory infections, malaria, dengue, kala azar, pre-eclampsia, and hypertension. Significant research gaps exist on child health, migrant health, and mental health. Integration of research evidence into policy, planning and program design is largely absent. However, prioritizing health for the National Adaptation Plan is an essential step towards establishing a climate-resilient health system.
Deciphering the Mechanism of Wogonin, a Natural Flavonoid, on the Proliferation of Pulmonary Arterial Smooth Muscle Cells by Integrating Network Pharmacology and In Vitro Validation
Authors: Cui Lidan , Zeng Zuomei , Wang Xinyue , Yuan Tianyi , Wang Can , Liu Dianlong , Guo Jian , Chen Yucai
Published: January 2023

Wogonin is one of the main active components of Scutellaria baicalensis, which has anti-inflammatory, anti-angiogenesis, and anti-fibrosis effects. Nevertheless, the effect of wogonin on pulmonary hypertension (PH) still lacks systematic research. This study aims to elucidate the potential mechanism of wogonin against PH through network pharmacology and further verify it through biological experiments in pulmonary arterial smooth muscle cells (PASMCs). The potential targets and pathways of wogonin against PH were predicted and analyzed by network pharmacology methods and molecular docking technology. Subsequently, the proliferation of PASMCs was induced by platelet-derived growth factor-BB (PDGF-BB). Cell viability and migration ability were examined. The method of Western blot was adopted to analyze the changes in related signaling pathways. Forty potential targets related to the effect of wogonin against PH were obtained. Based on the protein–protein interaction (PPI) network, gene-ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment, and molecular docking, it was shown that the effect of wogonin against PH is closely related to the proliferation of PASMCs and the hypoxia-inducible factor-1α (HIF-1α) pathway. A variety of results from biological experiments verified that wogonin can effectively inhibit the proliferation, migration, and phenotypic transformation of PDGF-BB-mediated PASMCs. In addition, the anti-proliferation effect of wogonin may be achieved by regulating HIF-1/ NADPH oxidase 4 (NOX4) pathway.
Cytochalasin B-Induced Membrane Vesicles from TRAIL-Overexpressing Mesenchymal Stem Cells Induce Extrinsic Pathway of Apoptosis in Breast Cancer Mouse Model
Authors: Chulpanova Daria S. , Pukhalskaia Tamara V. , Gilazieva Zarema E. , Filina Yuliya V. , Mansurova Milana N. , Rizvanov Albert A. , Solovyeva Valeriya V.
Published: January 2023

Tumor-necrosis-factor-associated apoptosis-inducing ligand (TRAIL) is one of the most promising therapeutic cytokines that selectively induce apoptosis in tumor cells. It is known that membrane vesicles (MVs) can carry the surface markers of parental cells. Therefore, MVs are of interest as a tool for cell-free cancer therapy. In this study, membrane vesicles were isolated from TRAIL-overexpressing mesenchymal stem cells using cytochalasin B treatment (CIMVs). To evaluate the antitumor effect of CIMVs-TRAIL in vivo, a breast cancer mouse model was produced. The animals were intratumorally injected with 50 µg of native CIMVs or CIMVs-TRAIL for 12 days with an interval of two days. Then, tumor growth rate, tumor necrotic area, the expression of the apoptosis-related genes CASP8, BCL-2, and BAX and the level of CASP8 protein were analyzed. A 1.8-fold increase in the CAS8 gene mRNA and a 1.7-fold increase in the CASP8 protein level were observed in the tumors injected with CIMVs-TRAIL. The expression of the anti-apoptotic BCL-2 gene in the CIMV-TRAIL group remained unchanged, while the mRNA level of the pro-apoptotic BAX gene was increased by 1.4 times, which indicated apoptosis activation in the tumor tissue. Thus, CIMVs-TRAIL were able to activate the extrinsic apoptosis pathway and induce tumor cell death in the breast cancer mouse model.
Cooperative Binding of SRSF3 to Structured 3’ss-α Exon RNA during α Exon Inclusion in the ZO-1 mRNA
Authors: Ruiz-Luis Tea Anastasia , Ortuño-Pineda Carlos , Galindo-Rosales José Manuel , Saucedo-Cárdenas Odila , Valdés Jesús
Published: January 2023

ZO-1α+ and ZO-1α− proteins are expressed in hermetic and leaky tight junctions, respectively. Two cis-acting distant exonic elements partly activate the 240 nucleotide-long α exon producing the ZO-1α+ isoform. However, the elements within and around the α exon and their respective factors involved in its splicing are unknown. To study the dynamic interaction between SRSF3 and its bioinformatically predicted target sites around the 3’ss upstream of the α exon during its activation, we performed EMSA, crosslinking, and in vivo splicing assays by ZO-1 minigene expression and siRNA-mediated silencing in transfected cells. Using V1 RNase, we probed the possible formation of a hairpin RNA structure between the intronic and proximal exonic SRSF3 binding sites. The hairpin sufficed for complex formations in the EMSA. The interaction of SRSF3 with the intronic site promoted the cooperative binding of SRSF3 to the exonic site. Finally, SRSF3 restored α exon activation in SRSF3 knockdown transfectants. Altogether, our results show that SRSF3–hairpin RNA interaction is crucial in the early recognition of 3’ss for α exon activation. It remains to be explored whether SRSF3 recruits or stabilizes the binding of other factors or brings separate splice sites into proximity.
Genome-Wide Identification and Analysis of the Heat-Shock Protein Gene in L. edodes and Expression Pattern Analysis under Heat Shock
Authors: Zhao Xu , Yin Kaiyong , Feng Rencai , Miao Renyun , Lin Junbin , Cao Luping , Ni Yanqing , Li Wensheng , Zhang Qin
Published: January 2023

Lentinula edodes (L. edodes), one of the most popular edible mushrooms in China, is adversely affected by high temperature. Heat shock proteins (HSPs) play a crucial role in regulating the defense responses against the abiotic stresses in L. edodes. Some HSPs in L. edodes have been described previously, but a genome-wide analysis of these proteins is still lacking. Here, the HSP genes across the entire genome of the L. edodes mushroom were identified. The 34 LeHSP genes were subsequently classified into six subfamilies according to their molecular weights and the phylogenetic analysis. Sequence analysis showed that LeHSP proteins from the same subfamily have conserved domains and one to five similar motifs. Except for Chr 5 and 9, 34 LeHSPs genes were distributed on the other eight chromosomes. Three pairs of paralogs were identified because of sequence alignment and were confirmed as arising from segmental duplication. In LeHSPs’ promoters, different numbers of heat shock elements (HSEs) were predicted. The expression profiles of LeHSPs in 18N44 and 18 suggested that the thermo-tolerance of strain 18N44 might be related to high levels of LeHSPs transcript in response to heat stress. The quantitative real-time PCR (qRT-PCR) analysis of the 16 LeHSP genes in strains Le015 and Le027 verified their stress-inducible expression patterns under heat stress. Therefore, these comprehensive findings provide useful in-depth information on the evolution and function of LeHSPs and lay a theoretical foundation in breeding thermotolerant L. edodes varieties.
Spatial Distribution of Citrus Pseudocercospora Leaf and Fruit Spot Disease and Shade Effect on Disease Intensity
Authors: Ndo E. G. D. , Akoutou Mvondo E. , Bella Manga F. , Bidzanga Nomo L. , Cilas C.
Published: January 2023

Adapting agricultural systems to face persistent environmental hazards is at the center of global concerns. In line with this, understanding and highlighting the structural characteristics of agroforestry systems could strengthen their resilience in terms of disease management. This study was conducted to evaluate the effect of shade on the intensity of citrus leaf and fruit spot disease caused by Pseudocercospora (PLFSD). Investigations to assess the effects of shade components on the incidence of PLFSD were carried out on 15-year-old tangerine trees in a cocoa-based agroforestry plot (Bokito) during four fruits seasons. Tangerines under the shade of large forest trees were compared to others located under full sunlight. A complementary experiment was conducted on young grapefruit plants in an orchard with mango and avocado groves in Foumbot. Three shading conditions, i.e., under avocado trees, under mango trees, and without shade, were explored. Data on shade and PLFSD incidence were collected and analyzed. Our findings show that PLFSD incidence was null on tangerine leaves from trees under shade compared to those under full sunlight. The same trends were observed in fruits under shade and under full sunlight. Disease incidence on grapefruit leaves was lower on trees under shade compared to those under full sunlight. In short, shade trees appear to constitute potential physical barriers to disease progression. This study also highlights disease spatial distribution as beyond 12 m of distance between neighboring trees, no spatial dependence of disease spread was observed. Management actions based on the distance between citrus trees and regulating shade are envisaged.