bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Mesorectal Excision vs. Transanal Endoscopic Microsurgery Followed by Radiotherapy for T2N0M0 Distal Rectal Cancer: A Multicenter Randomized Trial
Authors: Tang Junwei , Zhang Yue , Zhang Dongsheng , Zhang Chuan , Jin Kangpeng , Ji Dongjian , Peng Wen , Feng Yifei , Sun Yueming
Published: February 2022

Introduction

Transanal endoscopic microsurgery (TEM) is an organ-preserving treatment alternative for patients with early rectal cancer. However, TEM alone is associated with greater risk of local recurrence and inferior survival in comparison with total meso-rectal excision (TME). As an important adjuvant therapy, radiotherapy can effectively reduce the local recurrence rate of rectal cancer. This study aimed to investigate whether TEM followed by radiotherapy can be a valid alternative to TME in T2N0M0 distal rectal cancer treatment.

Methods

We plan to recruit 168 participants meeting established inclusion criteria. Following informed consent, participants will randomly receive treatment protocols of TEM followed by radiotherapy (a total dose of 45–50.4 Gy given in 25–28 factions) or TME. Depending on post-operative pathology, the participants will receive either long-term follow-up or further treatment. The primary endpoint of this trial is 3-year local recurrence rate. The secondary end points include 3-year disease-free survival rate, 3-year overall survival rate, 3-year mortality rate, post-operative quality of life, post-operative safety index, intraoperative evaluation index and post-operative short-term evaluation index.

Discussion

This trial is the first prospective randomized trial to investigate the rectum preserving treatment by using transanal local excision followed by radiotherapy.

Clinical trial registration

The trial was prospectively registered at ClinicalTrials.gov NCT04098471 on September 20, 2019.
Factors Impacting Chinese and European Vertical Fight Efficiency
Authors: Rosenow Judith , Chen Gong , Fricke Hartmut , Wang Yanjun
Published: February 2022

Increasing complexity due to a constantly growing number of target functions turns air traffic trajectory optimization into a multidimensional and nonlinear task that in turn necessitates a focus on the case-sensitive most important criteria. The criteria vary by continent and involve operational, economic, environmental, political, and social concerns. Furthermore, the requirements may alter for a single flight along its journey since air traffic is a transcontinental, segment-wise differently affected transportation mode. Tracked flight data allow for the observation and evaluation of large numbers of flights, as well as the extraction of criteria relevant to flight efficiency and to derive optimization strategies to improve it. In this study, flight track data of China and Europe were compared toward flight efficiency. We found major disparities in both continents’ routing structures. Historical ADS-B data considered to be reference trajectories were assessed for flight efficiency while putting a dedicated focus on the vertical profile. Criteria to optimize vertical flight efficiency (VFE) were derived. Based on the findings, suggestions for improvement towards trajectories with minimum fuel are formulated. Different optimization strategies were tested to identify important input variables and, if possible, to determine differences between operation in China and in Europe. On average and in both regions, the influence of weather (e.g., wind speed and wind direction) exceeds the influence of aerodynamics (aircraft type, mass), as the weather-optimized vertical profile more often results in minimum fuel consumption than the aerodynamically optimized trajectory. Atmospheric conditions, network requirements, aircraft types and flight planning procedures are similar in China and Europe and only have a minor impact on flight efficiency during the cruise phase. In a multi-criteria trajectory optimization of the extracted reference trajectories considering the weather, operational constraints and prohibited areas, we found that in China, on average, just under 13% fuel could be saved through optimal vertical and horizontal routing. In Europe, the figure is a good 10%. Furthermore, we calculated a fuel-saving potential of 8% in China and 3% in Europe through vertical adjustments of the trajectory alone. The resultant reference trajectories will be used for further analysis to increase the efficiency of continental air traffic flows.
A High Plant Density and the Split Application of Chemical Fertilizer Increased the Grain and Protein Content of Cowpea (Vigna unguiculata) in Burkina Faso, West Africa
Authors: Ishikawa Haruki , Batieno Benoît Joseph , Fatokun Christian , Boukar Ousmane
Published: February 2022

In West Africa, cowpea (Vigna unguiculata) is an important source of protein for many people. To meet the protein demands, the cowpea yields per unit area and its seed protein content must be increased. We evaluated the effects of the planting density and topdressing (fertilisation) timing on the cowpea yield and its protein content. High density (HD: 40 × 40 cm) and super high density (SHD: 40 × 20 cm) plantings were the most efficient approaches for enhancing cowpea yields. Across different regions in Burkina Faso, under such approaches, the yield significantly increased by as much as 214.5%, with an average value of 88.9%. Fertilisation was not required to achieve the significant increases in cowpea production following dense planting. Although the yield increased, the seed weight per plant decreased with the increase in planting density. Applying topdressing when the plants started flowering increased the seed protein content significantly by up to 24.4%. Simple and robust technologies, such as high-density planting and topdressing, can be rapidly disseminated for increased cowpea yields and protein content improvement for Burkina Faso and for other countries.
The Heart of the Killer Whale: Description of a Plastinated Specimen and Review of the Available Literature
Authors: Latorre Rafael , Graïc Jean-Marie , Raverty Stephen A. , Soria Federico , Cozzi Bruno , López-Albors Octavio
Published: February 2022

The killer whale (Orcinus orca, Linnaeus, 1958) is the largest extant delphinid. Despite its worldwide distribution in the wild and in dolphinariums, its anatomy remains relatively poorly described. In the present study, we describe the detailed morphology of a plastinated killer whale heart. The gross description of the arteries and veins reaching the organ and its coronary vessels are reported. Additional endoscopy and CT (computed tomography) scanning were performed to provide extensive measurements of its parts. In many aspects, the killer whale heart conformed to other delphinid heart descriptions, including position, relative size and shape and specific features such as extensive papillary muscles, trabecular endocardium and trabecula septomarginalis. These characteristics are representative of the delphinid family, suggesting that its functions and capacities are similar to that of other, smaller, dolphins and help understand the conditions in which these predators exert their remarkable physical performance necessary for their survival.
Practical Method for Freezing Buck Semen
Authors: Morrell Jane M. , Malaluang Pongpreecha , Ntallaris Theodoros , Johannisson Anders
Published: February 2022

Although several protocols for cryopreserving buck semen are described in the literature, they differ widely in factors such as season and method of semen collection, extender and sperm concentration. Therefore, choosing a protocol that is suitable for a particular on-farm situation can be problematic. In the present study, semen was collected by artificial vagina from seven bucks on a farm located approximately 90 minutes’ drive away from the laboratory, about 6 weeks before the start of the goat breeding season. The semen was immediately extended in warm semen extender containing soy lecithin and was placed in an insulated box with a cold pack for up to 4 h, during semen collection from the remaining bucks and subsequent transport to the laboratory. Following centrifugation at 4 °C and resuspension in the soy lecithin extender to a sperm concentration of 800 × 106 spermatozoa/mL, 0.25 mL plastic straws were filled and frozen in racks 4 cm above the surface of liquid nitrogen. This simple protocol resulted in an acceptable post-thaw quality for all seven bucks, with a mean post-thaw motility of 55 ± 21% and mean fragmented chromatin of 3.27 ± 1.39%. Normal sperm morphology was >90% in all ejaculates. The semen was sent to a gamete bank for long-term storage.
Effect of 15° Reverse Trendelenburg Position on Arterial Oxygen Tension during Isoflurane Anesthesia in Horses
Authors: Tucker Laura , Almeida Daniel , Wendt-Hornickle Erin , Baldo Caroline F. , Allweiler Sandra , Guedes Alonso G. P.
Published: February 2022

Lower than expected arterial oxygen tension (PaO2) continues to be an unresolved problem in equine anesthesia. The aim of this randomized, crossover, and prospective study using six adult horses is to determine if a 15° reverse Trendelenburg position (RTP) increases PaO2 during inhalation anesthesia. Under constant-dose isoflurane anesthesia, dorsally recumbent horses were positioned either horizontally (HP) or in a 15° RTP for 2 h. Lungs were mechanically ventilated (15 mL/kg, 6 breaths/min). Arterial carbon dioxide tension (PaCO2), PaO2, inspired oxygen fraction (FiO2), and end-tidal carbon dioxide tension (EtCO2) were determined every 30 min during anesthesia. Indices of dead-space ventilation (Vd/Vt), oxygenation (P–F ratio), and perfusion (F–shunt) were calculated. Dobutamine and phenylephrine were used to support mean arterial pressure (MAP). Data are presented as median and range. In one horse, which was deemed an outlier due to its thoracic dimensions and body conformation, indices of oxygenation worsened in RTP compared to HP (median PaO2 438 vs. 568 mmHg; P–F ratio 454 vs. 586 mmHg, and F–shunt 13.0 vs. 5.7 mmHg). This horse was excluded from calculations. In the remaining five horses they were significantly better with RTP compared to HP. Results in remaining five horses showed that PaO2 (502, 467–575 vs. 437, 395–445 mmHg), P-F ratio (518, 484–598 vs. 455, 407–458 mmHg), and F-shunt (10.1, 4.2–11.7 vs. 14.2, 13.8–16.0 mmHg) were significantly different between RTP and HP (p = 0.03). Other variables were not significantly different. In conclusion, the 15° RTP resulted in better oxygenation than HP in dorsally recumbent, isoflurane-anesthetized horses, although worsening of oxygenation may occur in individual horses. A study detailing the cardiovascular consequences of RTP is necessary before it can be recommended for clinical practice.
Association of Hard Ticks (Ixodidae) Infestation with Milk Production and Udder Health of Extensively Reared Dairy Goats
Authors: Vouraki Sotiria , Gelasakis Athanasios I. , Papanikolopoulou Vasiliki , Papadopoulos Elias , Arsenos Georgios
Published: February 2022

Extensively reared ruminants are seasonally exposed to ticks. Tick-related production losses and health issues have been well documented in cows and sheep but not in goats where relevant literature is scarce. The objective here was to investigate the association of hard tick infestation with milk production and udder health of dairy goats reared extensively. A cross-sectional study was carried out during May and June, in two dairy goat farms. The farms were located in Central and Northern Greece and were representative of typical extensive production systems. A total of 304 goats (n = 152 from each farm) were randomly selected. Each goat was examined for presence of hard ticks. Daily milk yield and quality characteristics were recorded. Udder health status was determined by milk somatic cell count (SCC) and total viable count (TVC). Tick infestation prevalence was 28.6%; it was associated with a significant (p < 0.001) increase in SCC and TVC (84.0% and 78.6%, respectively). The latter meant that infested goats were 3.7 times more prone to udder health problems (p < 0.001). There were not any significant effects (p > 0.05) on milk production. Overall, results suggest that control of tick infestation in extensively reared dairy goat herds is important for enhancing health and welfare status.
From In Vitro Data to In Vivo Interspecies Danger Communication: A Study of Chemosensing via the Mouse Grueneberg Ganglion
Authors: Lopes Ana Catarina , Brechbühl Julien , Ferreira Flavio , Amez-Droz Marjorie , Broillet Marie-Christine
Published: February 2022

In the wild, mice have developed survival strategies to detect volatile cues that warn them of potential danger. Specific olfactory neurons found in the Grueneberg ganglion olfactory subsystem can detect alarm pheromones emitted by stressed conspecifics, as well as kairomones involuntarily released by their predators. These volatile chemical cues allow intra- and interspecies communication of danger, respectively. Alarm pheromones, kairomones and bitter taste ligands share a common chemical motif containing sulfur or nitrogen. Interestingly, three specific bitter taste receptors (TAS2Rs) have been found in the Grueneberg ganglion neurons that are implicated in danger signalling pathways. We have recently developed a TAS2R–expressing heterologous system that mimics the Grueneberg ganglion neuron responses after kairomone stimulation. Here, we demonstrated by in vitro, ex vivo and in vivo experiments that the biological secretions from the raccoon (Procyon lotor) and the skunk (Mephitis mephitis) were acting as potent sources of kairomones. They activated the Grueneberg ganglion neurons and induced fear-related behaviours in mice. Identification of new sources of semiochemicals is a first step towards an understanding of the interspecies danger communication that takes place in the Grueneberg ganglion.
Impact of Early Season Temperatures in a Climate-Changed Atmosphere for Michigan: A Cool-Climate Viticultural Region
Authors: Schultze Steven R. , Sabbatini Paolo
Published: February 2022

This study assesses the impacts of observed (2001–2012) and projected climate change on early season heat accumulation for grape production (viticulture) in a cool-climate region of the world (Michigan, USA). Observational data were generated from a weather station located in the center of one of the most important appellations located in the SW part of the state. Climate change projections retrieved from a high spatiotemporal weather model using atmospheric conditions simulated for the end of the 21st Century. All the temperature variables considered demonstrated significant warming trends especially during the months of March, April and May. Temperature differences, increases in heat accumulation, and changes to potential frost events would necessitate new approaches to vineyard management. In fact, it is likely that vine budburst will occur earlier and early season frost develop as a new challenge. However, our study results are comparable with other viticulture regions of the world, with a warming trend of at least 3 to 5 °C in the months leading up to the growing season by the end of the 21st Century. Therefore, effective climate change adaptations will be important to the grape and wine industry in this region. Management strategies are needed to minimize climate risks while taking advantage of new opportunities related to improved climatic conditions for growing more late-ripening European Vitis vinifera grape varieties, relevant for producing higher quality wines.
Impact of Partial Volume Correction on [18F]GE-180 PET Quantification in Subcortical Brain Regions of Patients with Corticobasal Syndrome
Authors: Schuster Sebastian , Beyer Leonie , Palleis Carla , Harris Stefanie , Schmitt Julia , Weidinger Endy , Prix Catharina , Bötzel Kai , Danek Adrian , Rauchmann Boris-Stephan , Stöcklein Sophia , Lindner Simon , Unterrainer Marcus , Albert Nathalie L. , Mittlmeier Lena M. , Wetzel Christian , Rupprecht Rainer , Rominger Axel , Bartenstein Peter , Perneczky Robert , Levin Johannes , Höglinger Günter U. , Brendel Matthias , Dekorsy Franziska J.
Published: February 2022

Corticobasal syndrome (CBS) is a rare neurodegenerative condition characterized by four-repeat tau aggregation in the cortical and subcortical brain regions and accompanied by severe atrophy. The aim of this study was to evaluate partial volume effect correction (PVEC) in patients with CBS compared to a control cohort imaged with the 18-kDa translocator protein (TSPO) positron emission tomography (PET) tracer [18F]GE-180. Eighteen patients with CBS and 12 age- and sex-matched healthy controls underwent [18F]GE-180 PET. The cortical and subcortical regions were delineated by deep nuclei parcellation (DNP) of a 3D-T1 MRI. Region-specific subcortical volumes and standardized uptake values and ratios (SUV and SUVr) were extracted before and after region-based voxel-wise PVEC. Regional volumes were compared between patients with CBS and controls. The % group differences and effect sizes (CBS vs. controls) of uncorrected and PVE-corrected SUVr data were compared. Single-region positivity in patients with CBS was assessed by a >2 SD threshold vs. controls and compared between uncorrected and PVE-corrected data. Smaller regional volumes were detected in patients with CBS compared to controls in the right ventral striatum (p = 0.041), the left putamen (p = 0.005), the right putamen (p = 0.038) and the left pallidum (p = 0.015). After applying PVEC, the % group differences were distinctly higher, but the effect sizes of TSPO uptake were only slightly stronger due to the higher variance after PVEC. The single-region positivity of TSPO PET increased in patients with CBS after PVEC (100 vs. 83 regions). PVEC in the cortical and subcortical regions is valuable for TSPO imaging of patients with CBS, leading to the improved detection of elevated [18F]GE-180 uptake, although the effect sizes in the comparison against the controls did not improve strongly.
Cancer-Associated Fibroblasts and Tumor Cells in Pancreatic Cancer Microenvironment and Metastasis: Paracrine Regulators, Reciprocation and Exosomes
Authors: Sunami Yoshiaki , Häußler Johanna , Zourelidis Anais , Kleeff Jörg
Published: February 2022

Pancreatic cancer is currently the fourth leading cause of cancer deaths in the United States, and the overall 5 year survival rate is still only around 10%. Pancreatic cancer exhibits a remarkable resistance to established therapeutic options such as chemotherapy and radiotherapy, in part due to the dense stromal tumor microenvironment, where cancer-associated fibroblasts are the major stromal cell type. Cancer-associated fibroblasts further play a key role in cancer progression, invasion, and metastasis. Cancer-associated fibroblasts communicate with tumor cells, not only through paracrine as well as paracrine-reciprocal signaling regulators but also by way of exosomes. In the current manuscript, we discuss intercellular mediators between cancer-associated fibroblasts and pancreatic cancer cells in a paracrine as well as paracrine-reciprocal manner. Further recent findings on exosomes in pancreatic cancer and metastasis are summarized.
Roles of Protein Disulfide Isomerase in Breast Cancer
Authors: Yang Suhui , Jackson Chanel , Karapetyan Eduard , Dutta Pranabananda , Kermah Dulcie , Wu Yong , Wu Yanyuan , Schloss John , Vadgama Jaydutt V.
Published: February 2022

Protein disulfide isomerase (PDI) is the endoplasmic reticulum (ER)’s most abundant and essential enzyme and serves as the primary catalyst for protein folding. Due to its apparent role in supporting the rapid proliferation of cancer cells, the selective blockade of PDI results in apoptosis through sustained activation of UPR pathways. The functions of PDI, especially in cancers, have been extensively studied over a decade, and recent research has explored the use of PDI inhibitors in the treatment of cancers but with focus areas of other cancers, such as brain or ovarian cancer. In this review, we discuss the roles of PDI members in breast cancer and PDI inhibitors used in breast cancer research. Additionally, a few PDI members may be suggested as potential molecular targets for highly metastatic breast cancers, such as TNBC, that require more attention in future research.
A 40-Year Cohort Study of Evolving Hypothalamic Dysfunction in Infants and Young Children (<3 years) with Optic Pathway Gliomas
Authors: Picariello Stefania , Cerbone Manuela , D’Arco Felice , Gan Hoong-Wei , O’Hare Patricia , Aquilina Kristian , Opocher Enrico , Hargrave Darren , Spoudeas Helen A.
Published: February 2022

Despite high survival, paediatric optic pathway hypothalamic gliomas are associated with significant morbidity and late mortality. Those youngest at presentation have the worst outcomes. We aimed to assess presenting disease, tumour location, and treatment factors implicated in the evolution of neuroendocrine, metabolic, and neurobehavioural morbidity in 90 infants/children diagnosed before their third birthday and followed-up for 9.5 years (range 0.5–25.0). A total of 52 (57.8%) patients experienced endo-metabolic dysfunction (EMD), the large majority (46) of whom had hypothalamic involvement (H+) and lower endocrine event-free survival (EEFS) rates. EMD was greatly increased by a diencephalic syndrome presentation (85.2% vs. 46%, p = 0.001)), H+ (OR 6.1 95% CI 1.7–21.7, p 0.005), radiotherapy (OR 16.2, 95% CI 1.7–158.6, p = 0.017) and surgery (OR 4.8 95% CI 1.3–17.2, p = 0.015), all associated with anterior pituitary disorders. Obesity occurred in 25% of cases and was clustered with the endocrinopathies. Neurobehavioural deficits occurred in over half (52) of the cohort and were associated with H+ (OR 2.5 95% C.I. 1.1–5.9, p = 0.043) and radiotherapy (OR 23.1 C.I. 2.9–182, p = 0.003). Very young children with OPHG carry a high risk of endo-metabolic and neurobehavioural comorbidities which deserve better understanding and timely/parallel support from diagnosis to improve outcomes. These evolve in complex, hierarchical patterns over time whose aetiology appears predominantly determined by injury from the hypothalamic tumour location alongside adjuvant treatment strategies.
Pulsed Microwave Liver Ablation: An Additional Tool to Treat Hepatocellular Carcinoma
Authors: Zanus Giacomo , Tagliente Giovanni , Rossi Serena , Bonis Alessandro , Zambon Mattia , Scopelliti Michele , Brizzolari Marco , Grossi Ugo , Romano Maurizio , Finotti Michele
Published: February 2022

This study aimed to analyze the outcomes of HCC patients treated with a novel technique—pulsed microwave ablation (MWA)—in terms of safety, local tumor progression (LTP), intrahepatic recurrence (IHR), and overall survival (OS). A total of 126 pulsed microwave procedures have been performed in our center. We included patients with mono- or multifocal HCC (BCLC 0 to D). The LTP at 12 months was 9.9%, with an IHR rate of 27.8% at one year. Survival was 92.0% at 12 months with 29.4% experiencing post-operative complications (28.6% Clavien–Dindo 1–2, 0.8% Clavien–Dindo 3–4). Stratifying patients by BCLC, we achieved BCLC 0, A, B, C, and D survival rates of 100%, 93.2%, 93.3%, 50%, and 100%, respectively, at one year, which was generally superior to or in line with the expected survival rates among patients who are started on standard treatment. The pulsed MWA technique is safe and effective. The technique can be proposed not only in patients with BCLC A staging but also in the highly selected cases of BCLC B, C, and D, confirming the importance of the concept of stage migration. This procedure, especially if performed with a minimally invasive technique (laparoscopic or percutaneous), is repeatable with a short postoperative hospital stay.
Is There a Role for [18F]FDG PET-CT in Staging MALT Lymphoma?
Authors: Cohen Dan , Perry Chava , Hazut-Krauthammer Shir , Kesler Mikhail , Herishanu Yair , Luttwak Efrat , Even-Sapir Einat , Avivi Irit
Published: February 2022

The role of 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography—computed tomography (PET-CT) in assessing mucosa-associated lymphoid tissue (MALT) lymphoma is debatable. We retrospectively explored the role of [18F]FDG PET-CT in staging and predicting progression-free-survival (PFS) of patients with newly-diagnosed MALT lymphoma. Sixty-six studies were included. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were documented in the “hottest” extranodal and nodal lesions. Extranodal lesions and accompanying nodal disease were detected on PET in 38/66 (57.6%) and 13/66 (19.7%) studies, respectively. Detection rate of extranodal lesions differed significantly between those located in tissues with high/heterogeneous (e.g., stomach) vs low/homogenous (e.g., subcutaneous-tissue, lung) physiologic [18F]FDG-uptake (40.4% vs. 100%, p < 0.01). Nodal lesions had significantly lower SUVmax, MTV and TLG compared with extrandodal lesions in the same patients. Detection and [18F]FDG-avidity of extranodal lesions were higher in patients with advanced, bulky disease and concomitant marrow/nodal involvement. Increased SUVmax of extranodal lesions predicted shorter PFS (HR 1.10, 95% CI 1.01–1.19, p = 0.02). Higher SUVmax and TLG showed trends towards shorter PFS in patients with localized disease. In conclusion, detection rate of extranodal MALT lymphoma lesions located in tissues with low/homogeneous physiologic [18F]FDG-uptake is excellent on [18F]FDG PET-CT. When detected, SUVmax of extranodal lesions may predict PFS.
Expression of Immunomodulatory Checkpoint Molecules in Drug-Resistant Neuroblastoma: An Exploratory Study
Authors: Skertich Nicholas J. , Chu Fei , Tarhoni Imad A. M. , Szajek Stephen , Borgia Jeffrey A. , Madonna Mary Beth
Published: February 2022

Neuroblastoma is a common childhood cancer with poor prognosis when at its advanced stage. Checkpoint molecule inhibition is successful in treating multiple advanced adult cancers. We investigated PD-L1 and other checkpoint molecule expression to determine their roles in drug resistance and usefulness as targets for drug therapy. We developed three doxorubicin-resistant (DoxR) cell lines from parental cell lines. Matrigel in vitro invasion assays were used to compare invasiveness. Western blot assays were used to compare PD-L1 expression. Immuno-oncology checkpoint protein panels were used to compare concentrations of 17 checkpoint molecules both cellular and soluble. PD-L1 and 12 other checkpoint molecules were present in all cell lysates of each cell line without significantly different levels. Three were solubilized in the media of each cell line. PD-L1 is expressed in all DoxR and parental neuroblastoma cells and may be a potential target for drug therapy although its role in drug resistance remains unclear. Benchmarking checkpoint molecules provides the basis for future studies identifying targets for directed therapy and biomarkers for cancer detection or prognosis.
Conventional Therapies Do Not Prolong the Prognosis of Hepatocellular Carcinoma Patients with Extrahepatic Metastases under Receiving of Tyrosine Kinase Inhibitors
Authors: Maeda Hiroshi , Miura Kouichi , Morimoto Naoki , Watanabe Shunji , Tsukui Mamiko , Takaoka Yoshinari , Nomoto Hiroaki , Goka Rie , Sato Naoto , Morishima Kazue , Sakuma Yasunaru , Sata Naohiro , Fukushima Noriyoshi , Isoda Norio , Yamamoto Hironori
Published: February 2022

Background: Conventional therapies, including chemoembolization and radiation therapy, have been expected to prolong the prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases, which remains poor. However, little information is available on the efficacy of conventional therapies for such patients under tyrosine kinase inhibitor (TKI) treatment. Methods: We retrospectively investigated 127 HCC patients with extrahepatic metastases, who were divided into the non-TKI (conventional therapies) and TKI groups and further subdivided into the TKI alone and TKI plus conventional therapies groups. Conventional therapies included transcatheter arterial chemoembolization, cisplatin-based chemotherapy, radiation, surgery, and UFT, an oral chemotherapeutic agent. Results: The median of the overall survival (OS) of the 127 patients with extrahepatic metastases was 7.0 months. Meanwhile, the median OS of the TKI and non-TKI groups was 12.1 and 4.1 months, respectively. Imitating TKI after diagnosing metastases promoted a favorable increase in OS. Among the TKI group, the median OS in the TKI alone group was 8.9 months. TKI plus conventional therapies promoted no improvement in OS after adjusting for the patients’ background data. Conclusion: TKI promoted a better OS in HCC patients with extrahepatic metastases compared to conventional therapies. However, TKI plus conventional therapies promoted no improvement in the prognosis of such patients.
Advancing Treatment of Bone Metastases through Novel Translational Approaches Targeting the Bone Microenvironment
Authors: Sethakorn Nan , Heninger Erika , Sánchez-de-Diego Cristina , Ding Adeline B. , Yada Ravi Chandra , Kerr Sheena C. , Kosoff David , Beebe David J. , Lang Joshua M.
Published: February 2022

Bone metastases represent a lethal condition that frequently occurs in solid tumors such as prostate, breast, lung, and renal cell carcinomas, and increase the risk of skeletal-related events (SREs) including pain, pathologic fractures, and spinal cord compression. This unique metastatic niche consists of a multicellular complex that cancer cells co-opt to engender bone remodeling, immune suppression, and stromal-mediated therapeutic resistance. This review comprehensively discusses clinical challenges of bone metastases, novel preclinical models of the bone and bone marrow microenviroment, and crucial signaling pathways active in bone homeostasis and metastatic niche. These studies establish the context to summarize the current state of investigational agents targeting BM, and approaches to improve BM-targeting therapies. Finally, we discuss opportunities to advance research in bone and bone marrow microenvironments by increasing complexity of humanized preclinical models and fostering interdisciplinary collaborations to translational research in this challenging metastatic niche.
The Role of Macroautophagy and Chaperone-Mediated Autophagy in the Pathogenesis and Management of Hepatocellular Carcinoma
Authors: Karampa Anastasia D. , Goussia Anna C. , Glantzounis Georgios K. , Mastoridou Eleftheria M. , Anastasopoulos Nikolaos-Andreas T. , Charchanti Antonia V.
Published: February 2022

Hepatocarcinogenesis is a long process with a complex pathophysiology. The current therapeutic options for HCC management, during the advanced stage, provide short-term survival ranging from 10–14 months. Autophagy acts as a double-edged sword during this process. Recently, two main autophagic pathways have emerged to play critical roles during hepatic oncogenesis, macroautophagy and chaperone-mediated autophagy. Mounting evidence suggests that upregulation of macroautophagy plays a crucial role during the early stages of carcinogenesis as a tumor suppressor mechanism; however, it has been also implicated in later stages promoting survival of cancer cells. Nonetheless, chaperone-mediated autophagy has been elucidated as a tumor-promoting mechanism contributing to cancer cell survival. Moreover, the autophagy pathway seems to have a complex role during the metastatic stage, while induction of autophagy has been implicated as a potential mechanism of chemoresistance of HCC cells. The present review provides an update on the role of autophagy pathways in the development of HCC and data on how the modulation of the autophagic pathway could contribute to the most effective management of HCC.
Heterochromatin Protein 1: A Multiplayer in Cancer Progression
Authors: Jeon Yu Hyun , Kim Go Woon , Kim So Yeon , Yi Sang Ah , Yoo Jung , Kim Ji Yoon , Lee Sang Wu , Kwon So Hee
Published: February 2022

Dysregulation of epigenetic mechanisms as well as genomic mutations contribute to the initiation and progression of cancer. In addition to histone code writers, including histone lysine methyltransferase (KMT), and histone code erasers, including histone lysine demethylase (KDM), histone code reader proteins such as HP1 are associated with abnormal chromatin regulation in human diseases. Heterochromatin protein 1 (HP1) recognizes histone H3 lysine 9 methylation and broadly affects chromatin biology, such as heterochromatin formation and maintenance, transcriptional regulation, DNA repair, chromatin remodeling, and chromosomal segregation. Molecular functions of HP1 proteins have been extensively studied, although their exact roles in diseases require further study. Here, we comprehensively review the studies that have revealed the altered expression of HP1 and its functions in tumorigenesis. In particular, the distinctive effects of each HP1 subtype, namely HP1α, HP1β, and HP1γ, have been thoroughly explored in various cancer types. We also highlight how HP1 can serve as a potential biomarker for cancer prognosis and therapeutic target for cancer patients.
BKV Related Hemorrhagic Cystitis—An Insight into Risk Factors and Later Complications—An Analysis on Behalf of Polish Adult Leukemia Group
Authors: Dybko Jarosław , Piekarska Agnieszka , Agrawal Siddarth , Makuch Sebastian , Urbaniak-Kujda Donata , Biernat Monika , Rybka Blanka , Dutka Magdalena , Sadowska-Klasa Alicja , Giebel Sebastian , Gil Lidia
Published: February 2022

BK virus reactivation increases the likelihood of hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplant (HCT). In this study, we aimed to identify predictive and risk factors associated with the increased occurrence of this condition following HCT. On a group of 124 patients aged ≤71 years old (median 40 years) who underwent HCT, we analyzed sex, age, time from diagnosis to transplantation, type of conditioning, donor’s relationship, age, and sex, the impact of immunosuppression with different drugs, and acute and chronic GVHD, BK viremia and viruria as potential factors increasing the risk of BK-related HC after HCT. HC occurred among 24 patients (24/124; 29.2%). A significant correlation was observed between HC incidences after HCT, BK viremia and viruria, and acute GVHD occurrence. Furthermore, the level of BKV DNA in serum at day +21 (>0.75 × 103) significantly impacted the patients’ survival time. According to our results, the likelihood ratio of BKV-DNA on day +21 in serum is 6.25, indicating that this diagnostic test has the potential to be utilized in a clinical setting. These findings may be used as a voice in the discussion on implementing an optimal preemptive treatment in BKV reactivation after allogeneic HCT.
Limited Metabolic Effect of the CREBRFR457Q Obesity Variant in Mice
Authors: Metcalfe Louise K. , Shepherd Peter R. , Smith Greg C. , Turner Nigel
Published: February 2022

The Arg457Gln missense variant in the CREBRF gene has previously been identified as driving excess body weight in Pacific/Oceanic populations. Intriguingly, Arg457Gln variant carriers also demonstrate paradoxical reductions in diabetes risk, indicating that the gene has a critical role in whole-body metabolism. To study the function of this variant in more detail, we generated mice on an FVB/N background with the Crebrf Arg458Gln variant knocked in to replace the endogenous Crebrf. The whole-body metabolic phenotype was characterized for male and female mice on a regular chow diet or an 8-week high-fat challenge. Regular assessment of body composition found that the Crebrf variant had no influence on total body weight or fat mass at any time point. Glucose tolerance tests demonstrated no obvious genotype effect on glucose homeostasis, with indirect calorimetry measures of whole-body energy expenditure likewise unaffected. Male chow-fed variant carriers displayed a trend towards increased lean mass and significantly reduced sensitivity to insulin administration. Overall, this novel mouse model showed only limited phenotypic effects associated with the Crebrf missense variant. The inability to recapitulate results of human association studies may invite reconsideration of the precise mechanistic link between CREBRF function and the risks of obesity and diabetes in variant allele carriers.
Proteomic Studies of Roots in Hypoxia-Sensitive and -Tolerant Tomato Accessions Reveal Candidate Proteins Associated with Stress Priming
Authors: Czernicka Małgorzata , Kęska Kinga , Planchon Sébastien , Kapusta Małgorzata , Popielarska-Konieczna Marzena , Wesołowski Wojciech , Szklarczyk Marek , Renaut Jenny
Published: February 2022

Tomato (Solanum lycopersicum L.) is a vegetable frequently exposed to hypoxia stress induced either by being submerged, flooded or provided with limited oxygen in hydroponic cultivation systems. The purpose of the study was to establish the metabolic mechanisms responsible for overcoming hypoxia in two tomato accessions with different tolerance to this stress, selected based on morphological and physiological parameters. For this purpose, 3-week-old plants (plants at the juvenile stage) of waterlogging-tolerant (WL-T), i.e., POL 7/15, and waterlogging-sensitive (WL-S), i.e., PZ 215, accessions were exposed to hypoxia stress (waterlogging) for 7 days, then the plants were allowed to recover for 14 days, after which another 7 days of hypoxia treatment was applied. Root samples were collected at the end of each time-point and 2D-DIGE with MALDI TOF/TOF, and expression analyses of gene and protein-encoded alcohol dehydrogenase (ADH2) and immunolabelling of ADH were conducted. After collating the obtained results, the different responses to hypoxia stress in the selected tomato accessions were observed. Both the WL-S and WL-T tomato accessions revealed a high amount of ADH2, which indicates an intensive alcohol fermentation pathway during the first exposure to hypoxia. In comparison to the tolerant one, the expression of the adh2 gene was about two times higher for the sensitive tomato. Immunohistochemical analysis confirmed the presence of ADH in the parenchyma cells of the cortex and vascular tissue. During the second hypoxia stress, the sensitive accession showed a decreased accumulation of ADH protein and similar expression of the adh2 gene in comparison to the tolerant accession. Additionally, the proteome showed a greater protein abundance of glyceraldehyde-3-phosphate dehydrogenase in primed WL-S tomato. This could suggest that the sensitive tomato overcomes the oxygen limitation and adapts by reducing alcohol fermentation, which is toxic to plants because of the production of ethanol, and by enhancing glycolysis. Proteins detected in abundance in the sensitive accession are proposed as crucial factors for hypoxia stress priming and their function in hypoxia tolerance is discussed.
Superhydrophobic Composite Coating with Excellent Mechanical Durability
Authors: Ke Cheng , Fang Yifan , Zhou Zheng , Wang Guohong , Liu Yongjia , Wu Wei , Xiao Lishuang , Zhang Mengzhuo , Hu Haibao , Liu Jianxi
Published: February 2022

Superhydrophobic surfaces have great potential for self-cleaning, anti-icing, and drag-reducing because of their water repellency property. However, their super-hydrophobicity is destroyed under mechanical abrasion due to the vulnerability of the delicate surface textures. Here, we demonstrate a strategy to create a robust superhydrophobic surface using MXene and fluoridated silica as functional fillers in epoxy resin. The fluoridated silica produces low surface energy, MXene serves as a wear-resistant phase and epoxy resin is the binding matrix. The composite coating demonstrates a self-cleaning effect to remove particles from the superhydrophobic surface by rolling water droplets. Moreover, the coating exhibits excellent mechanical durability by standing abrasion to maintain super-hydrophobicity. The superhydrophobic composite coating has the advantages of low cost and feasibility and has the potential for expandable industrial promotion.
Tribocorrosion Behavior of Laser Cladded Ti-Al-(C, N) Composite Coatings in Artificial Seawater
Authors: Feng Jinyu , Xiao Huaqiang
Published: February 2022

MAX phase containing Ti-Al-(C, N) composite coatings is promising in marine engineering due to the improved tribocorrosion performance of titanium alloys. Therefore, novel Ti-Al-(C, N) composite coatings were prepared in this study using laser cladding on TC4 substrate. Electrochemical performances of as-obtained composite coatings were then analyzed under static and dynamic conditions in an artificial seawater environment, and their tribocorrosion behaviors and corrosion–wear synergism mechanism were examined by a tribocorrosion test system. The results showed that the existence of self-lubricating phases Ti2AlC and Ti2AlN in composite coatings and the corrosion products with a certain lubrication effect generated during the friction process kept the average friction coefficient at a low level. With the increase of load, the mechanical failure of the passive film in the friction process was enhanced, the adsorption of corrosive medium on the surface of the passive film led to its active dissolution, and the wear volume increased from 1.45 × 10−2 to 3.24 × 10−2 mm3. The corrosion of composite coatings in artificial seawater was not extensive, and volume loss caused by tribocorrosion was mainly determined by wear behavior. In sumary, the coatings exhibited good bearing capacity in the marine environment, thereby showing broad prospects for marine equipment applications.
Influence of Precursor Density and Conversion Time on the Orientation of Vapor-Deposited ZIF-8
Authors: Kräuter Marianne , Cruz Alexander John , Stassin Timothée , Rodríguez-Hermida Sabina , Ameloot Rob , Resel Roland , Coclite Anna Maria
Published: February 2022

ZIF-8 was synthesized by subjecting ZnO thin films deposited via plasma-enhanced atomic layer deposition to a 2-methylimidazole vapor. The impact of the conversion time as well as the density and thickness of the ZnO precursor on the resulting ZIF-8 layers were investigated. Grazing Incidence X-ray diffraction reveals a preferred (100) or (111) orientation of the ZIF-8 crystals, depending on thickness and density of the precursor, and with a more prominent orientation at longer conversion times. The onset of crystallization occurs after 20 min of conversion for the less dense precursor, compared to 40 min for the denser one. The ZIF-8 thickness and roughness increase with conversion time. The final thickness of the ZIF-8 layer depends on the thickness and density of the precursor layer, and can be up to 15-fold higher than the precursor thickness.
Virtual Resection: A New Tool for Preparing for Nephron-Sparing Surgery in Wilms Tumor Patients
Authors: van der Zee Jasper M. , Fitski Matthijs , Simonis Frank F. J. , van de Ven Cornelis P. , Klijn Aart J. , Wijnen Marc H. W. A. , van der Steeg Alida F. W.
Published: February 2022

Nephron-sparing surgery (NSS) in Wilms tumor (WT) patients is a surgically challenging procedure used in highly selective cases only. Virtual resections can be used for preoperative planning of NSS to estimate the remnant renal volume (RRV) and to virtually mimic radical tumor resection. In this single-center evaluation study, virtual resection for NSS planning and the user experience were evaluated. Virtual resection was performed in nine WT patient cases by two pediatric surgeons and one pediatric urologist. Pre- and postoperative MRI scans were used for 3D visualization. The virtual RRV was acquired after performing virtual resection and a questionnaire was used to assess the ease of use. The actual RRV was derived from the postoperative 3D visualization and compared with the derived virtual RRV. Virtual resection resulted in virtual RRVs that matched nearly perfectly with the actual RRVs. According to the questionnaire, virtual resection appeared to be straightforward and was not considered to be difficult. This study demonstrated the potential of virtual resection as a new planning tool to estimate the RRV after NSS in WT patients. Future research should further evaluate the clinical relevance of virtual resection by relating it to surgical outcome.
Feasibility, Acceptability, and Clinical Significance of a Dyadic, Web-Based, Psychosocial and Physical Activity Self-Management Program (TEMPO) Tailored to the Needs of Men with Prostate Cancer and Their Caregivers: A Multi-Center Randomized Pilot Trial
Authors: Lambert Sylvie D. , Duncan Lindsay R. , Culos-Reed S. Nicole , Hallward Laura , Higano Celestia S. , Loban Ekaterina , Katz Anne , De Raad Manon , Ellis Janet , Korman Melissa B. , Sears Carly , Ibberson Cindy , Walker Lauren , Belzile Eric , Saha-Chaudhuri Paramita , McTaggart-Cowan Helen , Peacock Stuart
Published: February 2022

Background: Prostate cancer is the most common cancer diagnosis among men. Family caregivers (often female spouses) play a key role in ensuring patients’ needs are met, frequently assuming their role with no formal training, which can contribute to a high burden. The purpose of this study was to pilot TEMPO—the first dyadic, Tailored, wEb-based, psychosocial and physical activity self-Management PrOgram for men with prostate cancer and their caregivers. Methods: 49 men with prostate cancer and their caregivers were randomized to TEMPO or usual care. Baseline and follow-up questionnaires were completed to assess feasibility, acceptability, and clinical significance. A priori benchmarks for these outcomes were set. Thirteen exit interviews were conducted to further explore acceptability. Results: Feasibility benchmarks were met with the exception for recruitment with on average 6.1 dyads recruited/month (benchmark: 8 dyads/month). Benchmarks of acceptability focused on attrition (<25%) and system usability, which were met. Using the strict criteria for adherence of 100% of the module viewed and participants spending at least 15 min on the module, 45% of participants were adherent. The clinical significance on anxiety and quality of life was supported for caregivers, and mostly supported for the men with prostate cancer. Conclusion: This pilot trial was successful, with minor modifications needed prior to a large trial.
Phylogeography and Genetic Structure of Sand Dune Specialist Stilpnolepis centiflora (Asteraceae) in Northwest China Revealed by Molecular Data
Authors: Shi Xiaojun , Jiang Xiaolong , Zhang Hongxiang , Qiu Juan
Published: February 2022

Stilpnolepis centiflora is an endemic annual herb in the Asteraceae family found across five sand deserts in Northwest China. We aimed to investigate the genetic structure of S. centiflora and attempt to link species evolution with desert formation during the Pleistocene era. We used sequence data from nuclear and chloroplast genes to investigate genetic diversity among 28 populations. We analyzed sequence data using network analysis, spatial analysis of molecular variance (SAMOVA), and a Mantel test. We then used a molecular clock to place the genetic patterns in a temporal framework and tested for signals of expansion using neutrality tests and by determining mismatch distributions. Six distinct haplotypes and 31 ribotypes were identified. Significant chloroplast DNA population subdivision was detected (GST = 0.952; NST = 0.976), but only moderate nrDNA subdivision (GST = 0.360; NST = 0.579) was detected. SAMOVA revealed four diverging groups of related haplotypes, coinciding with the boundaries of deserts. Molecular dating suggests that the clades representing different deserts diverged from 1.2 to 0.20 Ma, concordant with the Kun-Huang Movement of Qinghai Tibet Plateau uplift and a glacial event (Naynayxungla) during the Middle–Late Pleistocene. The disjunction of S. centiflora among different deserts was correspondingly reflected in the examined genetic traits with consistent spatiotemporal evolution between species and deserts. Therefore, the evolutionary dynamics of S. centiflora appear to have been driven by geological movement and climate change. The patterns described here are potentially useful to conservation biologists and may serve as a model for other sand-obligate organisms found in the deserts of Northwest China.