bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathological, molecular and prognostic characteristics of cancer of unknown primary in China: An analysis of 1420 cases
Authors: Qi Peng , Sun Yifeng , Liu Xin , Wu Sheng , Wo Yixin , Xu Qinghua , Wang Qifeng , Hu Xichun , Zhou Xiaoyan
Published: July 2022

Background

Cancer of unknown primary (CUP) is defined the presence of metastatic disease without an identified primary site. An unidentifiable primary site of cancer creates significant challenges for treatment selection. We aimed to describe the clinicopathological, molecular, and prognostic characteristics of Chinese CUP patients.

Methods

Patients with oncologist‐confirmed CUP were identified at Fudan University Shanghai Cancer Center from 2019 to 2020. Information on patient characteristics, tumor presentation, treatment, and outcome were retrospectively collected from the inpatient database and pathological consultation database for descriptive analysis. A multivariable logistic regression model was established to identify factors associated with patient prognosis.

Results

A total of 1420 CUP patients were enrolled in this study. The baseline characteristics of the entire cohort included the following: median age (59 years old), female sex (45.8%), adenocarcinoma (47.7%), and poorly differentiated or undifferentiated tumors (92.1%). For the inpatient cohort, the most common sites where cancer spread included the lymph nodes (41.8%), bone (22.0%), liver (20.1%), and peritoneum/retroperitoneum (16.0%). A total of 77.4% and 58.2% of patients were treated with local therapy and systemic therapy, respectively. Four prognostic factors, including liver metastasis, peritoneal/retroperitoneal metastasis, number of metastatic sites (N ≥ 2), and systemic treatment, were independently associated with overall survival. Additionally, 24.8% (79/318) of patients received molecular testing, including PD‐L1, human papillomavirus, genetic variation, and 90‐gene expression tests for diagnosis or therapy selection.

Conclusion

Cancer of unknown primary remains a difficult cancer to diagnose and manage. Our findings improve our understanding of Chinese CUP patient characteristics, leading to improved care and outcomes for CUP patients.
Detection of methylated BCAT1 and IKZF1 after curative‐intent treatment as a prognostic indicator for colorectal cancer recurrence
Authors: Pedersen Susanne K. , Symonds Erin L. , Roy Amitesh C. , Cornthwaite Kathryn J. , LaPointe Lawrence C. , Young Graeme P.
Published: July 2022

Background

The risk of recurrence after completion of curative‐intent treatment of colorectal cancer (CRC) is hard to predict. Post‐treatment assaying for circulating tumor DNA (ctDNA) is an encouraging approach for stratifying patients for therapy, but the prognostic value of this approach is less explored. This study aimed to determine if detection of methylated BCAT1 and IKZF1 following completion of initial treatment identified patients with a poorer recurrence‐free survival (RFS).

Methods

142 CRC stage I‐III cases with at least 2 years of follow up (unless recurrence was evident sooner) and a methylated BCAT1/IKZF1 test result between 2 weeks and 12 months after completion of initial treatment were eligible for study inclusion. The association between BCAT1/IKZF1 and RFS was assessed by the log‐rank (Mantel‐Cox) method. Cox proportional hazard regression analysis was used for multivariable survival analysis.

Results

Thirty‐three (23.2%) had recurrence at a median 1.6y (interquartile range: 0.8–2.4). Methylated BCAT1/IKZF1 was detected in 19 of the 142 patients (13.4%) and was associated with a significant risk of recurrence (hazard ratio [HR] 5.7, 95%CI: 1.9–17.3, p = 0.002). Three‐year RFS for patients with or without detectable methylated BCAT1/IKZF1 was 56.5% and 83.3%, respectively. Multivariable analysis showed that detection of methylated BCAT1/IKZF1 (HR = 2.6, p = 0.049) and site of the primary tumor (HR = 4.2, p = 0.002) were the only significant prognostic indicators of poor RFS.

Conclusions

BCAT1/IKZF1 methylation testing after curative‐intent treatment is an independent prognostic indicator for RFS and identifies a subgroup at high risk. Personalized surveillance is warranted for patients with these ctDNA biomarkers detectable after curative‐intent treatment.
Patterns and prognosis of regional recurrence in nasopharyngeal carcinoma after intensity‐modulated radiotherapy
Authors: Xiao Xiao‐Tang , Wu Yi‐Shan , Chen Yu‐Pei , Liu Xu , Guo Rui , Tang Ling‐Long , Ma Jun , Li Wen‐Fei
Published: July 2022

Objective

We analyzed the patterns of lymph node (LN) failure and prognosis in patients with regional recurrent nasopharyngeal carcinoma (rNPC) alone after primary intensity‐modulated radiotherapy (IMRT).

Methods

A total of 175 patients who were treated with IMRT between 2010 and 2015 and who experienced regional recurrence alone were included. Recurrent LNs were re‐located in the initial pretreatment imaging and IMRT plan and failures were classified as in‐field or out‐field based on target volume delineation. All patients underwent curative salvage treatment. Independent prognostic factors for overall survival (OS) were selected by multivariate Cox analysis.

Results

Level IIb (49.1%, 86/175) was the most frequent recurrence site, followed by level IIa (36%), level III (18.9%), level IVa (12%), the retropharyngeal region (8%), level Va (6.9%), and the parotid region (6.9%). A total of 264 recurrent LNs were recorded: 149 (56.4%) were classified as in‐field failure with a prescribed dose ≥66 Gy, 60 (22.7%) with 60 to <66 Gy, 32 (12.1%) with 50 to <60 Gy, and 23 (8.7%) as an out‐field failure, which mainly occurred in the parotid region and level Ib. After a median follow‐up of 52.8 months, the estimated 5‐year OS rate was 66.9%. Multivariate analysis showed that age, plasma Epstein–Barr virus DNA level, extranodal extension, lower neck involvement, and parotid LN recurrence were independent prognostic factors of OS.

Conclusions

In‐field failure represented the main pattern of regional recurrence and out‐field failure mainly occurred in the parotid gland and level Ib. Patients with regional rNPC alone had a good prognosis after salvage treatment.
Breast cancer brain metastasis: Current evidence and future directions
Authors: Sun Hongna , Xu Junnan , Dai Shuang , Ma Yiwen , Sun Tao
Published: July 2022

Breast cancer is the most common cancer in women and the second leading cause of cancer‐related deaths after lung cancer. Metastasis of the central nervous system is a terrible event for breast cancer patients, affecting their survival and quality of life. Compared with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative breast cancer patients, brain metastases are more likely to affect patients with triple‐negative breast cancer and human epidermal growth factor receptor 2‐positive breast cancer. The treatment of breast cancer has improved greatly in the last two decades. However, brain metastases from breast cancer remain the leading cause of morbidity and mortality. Patients with breast cancer brain metastasis have been in an inferior position due to the lack of clinical research in this field, and they are often explicitly excluded from almost all clinical trials. The occurrence and progression of brain metastases will result in severe cognitive impairment and adverse physical consequences, so we must have a good understanding of the molecular mechanisms of breast cancer brain metastasis. In this article, we have retrieved the latest literature of molecules and pathways associated with breast cancer brain metastasis, summarized common therapy strategies, and discussed the prospects and clinical implications of targeting the molecules involved.
U.S. Supreme Court limits emotional distress damages in Title IX and other cases
Authors: Lyerly Eric
Published: July 2022

A recent U.S. Supreme Court case is making waves in higher education law. Although the case didn't involve a student, faculty member, or university, the ruling could shape legal outcomes for higher education cases involving Title VI, Title IX, and the Rehabilitation Act.
Bile acid‐based advanced drug delivery systems, bilosomes and micelles as novel carriers for therapeutics
Authors: Nemati Mohadeseh , Fathi‐Azarbayjani Anahita , Al‐Salami Hani , Roshani Asl Elmira , Rasmi Yousef
Published: July 2022

Diabetes mellitus affects almost half a billion patients worldwide and results from either destruction of β‐cells responsible for insulin secretion or increased tissue resistance to insulin stimulation and the reduction of glycemic control. Novel drug delivery systems can improve treatment efficacy in diabetic patients. The low aqueous solubility of most oral antidiabetic drugs decreases drug bioavailability; therefore, there is a demand for the use of novel methods to overcome this issue. The application of bile acids mixed micelles and bilosomes can provide an enhancement in drug efficacy. Bile acids are amphiphilic steroidal molecules that contain a saturated tetracyclic hydrocarbon cyclopentanoperhydrophenanthrene ring, and consist of three 6‐membered rings and a 5‐membered ring, a short aliphatic side chain, and a tough steroid nucleus. This review offers a comprehensive and informative data focusing on the great potential of bile acid, their salts, and their derivatives for the development of new antidiabetic drug delivery system.
Endogenous Proteins Modulation in Live Cells with Small Molecules and Light
Authors: Zeng Kaixing , Han Lili , Chen Yiyun
Published: July 2022

Protein modulation by light illumination enables the investigation of biological function in high spatiotemporal precision. Compared to genetic methods, the small molecule approach is uniquely suited for modulating endogenous proteins. Endogenous protein modulation in live cells with small molecules and light has recently advanced on three distinctive frontiers: i) the infrared‐light‐induced or localized decaging of small molecules by photolysis, ii) the visible‐light‐induced photocatalytic releasing of small molecules, and iii) the small‐molecule‐ligand‐directed caging for photomodulation of proteins. Together, these methods provide powerful chemical biology tool kits for spatiotemporal modulation of endogenous proteins with potential therapeutic applications. This Concept article aims to inspire organic chemists and chemical biologists to delve into this burgeoning endogenous protein modulation field for new biological discoveries.
siRNA‐based nanotherapeutics as emerging modalities for immune‐mediated diseases: A preliminary review
Authors: Sargazi Saman , Arshad Rabia , Ghamari Reza , Rahdar Abbas , Bakhshi Ali , Karkan Sonia Fathi , Ajalli Narges , Bilal Muhammad , Díez‐Pascual Ana M.
Published: July 2022

Immune‐mediated diseases (IMDs) are chronic conditions that have an immune‐mediated etiology. Clinically, these diseases appear to be unrelated, but pathogenic pathways have been shown to connect them. While inflammation is a common occurrence in the body, it may either stimulate a favorable immune response to protect against harmful signals or cause illness by damaging cells and tissues. Nanomedicine has tremendous promise for regulating inflammation and treating IMIDs. Various nanoparticles coated with nanotherapeutics have been recently fabricated for effective targeted delivery to inflammatory tissues. RNA interference (RNAi) offers a tremendous genetic approach, particularly if traditional treatments are ineffective against IMDs. In cells, several signaling pathways can be suppressed by using RNAi, which blocks the expression of particular messenger RNAs. Using this molecular approach, the undesirable effects of anti‐inflammatory medications can be reduced. Still, there are many problems with using short‐interfering RNAs (siRNAs) to treat IMDs, including poor localization of the siRNAs in target tissues, unstable gene expression, and quick removal from the blood. Nanotherapeutics have been widely used in designing siRNA‐based carriers because of the restricted therapy options for IMIDs. In this review, we have discussed recent trends in the fabrication of siRNA nanodelivery systems, including lipid‐based siRNA nanocarriers, liposomes, and cationic lipids, stable nucleic acid‐lipid particles, polymeric‐based siRNA nanocarriers, polyethylenimine (PEI)‐based nanosystems, chitosan‐based nanoformulations, inorganic material‐based siRNA nanocarriers, and hybrid‐based delivery systems. We have also introduced novel siRNA‐based nanocarriers to control IMIDs, such as pulmonary inflammation, psoriasis, inflammatory bowel disease, ulcerative colitis, rheumatoid arthritis, etc. This study will pave the way for new avenues of research into the diagnosis and treatment of IMDs.
tert‐Butylhydroquinone‐induced formation of high‐molecular‐weight p62: A novel mechanism in the activation of Nrf2‐Keap1
Authors: Chen Yunfang , Cao Hua , He Wan , Zhang Xi , Xu Ruilian
Published: July 2022

The respiratory system is always exposed to air and is most vulnerable to attack by environmental free radicals. The nuclear factor E2‐related factor 2–Kelch‐like ECH‐associated protein 1–antioxidant response element (Nrf2‐Keap1‐ARE) pathway and p62 are both involved in the oxidative stress response. However, the interplay between these two systems remains largely unknown. This study shows that treatment of L2 cells with tert‐Butylhydroquinone (tBHQ) generates a high‐molecular‐weight (HMW) form of p62, leading to activation of the Nrf2‐Keap1‐ARE pathway. The levels of HMW‐p62 increased as the tBHQ concentration increased, with concomitant decreases seen in the classical form of p62. Moreover, small interfering RNA targeting p62 increases Keap1 protein levels and inactivates the Nrf2‐Keap1‐ARE pathway. These results demonstrate that the Nrf2‐Keap1 pathway is partially regulated by p62. tBHQ‐induced HMW‐p62 production may be a novel mechanism in the activation of the Nrf2‐Keap1‐ARE pathway.
Recognizing Design Issues in Process Industry for Safer Design
Authors: Zakaria Zafirah , Mahmud Hafizah , Kidam Kamarizan
Published: July 2022

In this study, accident cause analysis was used to generate a number of design failure elements (DFEs) that highlight the general classification of design errors. Then, a database of cases, suggesting design changes from unsafe to safe design, was compiled from journals, accident corrective action, and patents to identify the chemical industry design issues (DIs). The DIs were then classed under DFEs and into five main equipment categories, namely, reaction, separation, heat transfer, storage, and pipe and piping system. The database analysis reveals that the layout accounts for 17.4 % of DFEs, followed by equipment error (17.29 %) and reaction and reactive condition (16.86 %). For the equipment category, the reaction equipment had the highest DI which was related to the DFE of reaction and the reactive condition.
Temperature Difference‐Based Fouling Detection in the Heat Exchanger of Gas‐Solid Fluidized Beds
Authors: Choi Jae Won , Shin Seokhee , Park Soo Youp , Youn Pil-Sang , Yu Seungho , Kim Daewook , Choi Jeong-Hoo , Kim Ki Chul
Published: July 2022

Despite the harmfulness of absorbent fouling, its fundamental understanding is limited. The fouling behaviors in fluidized beds charged by CO2 absorbent particles were therefore examined under various physical conditions to identify key parameters that can assist in the direct detection of absorbent fouling. The results demonstrate that the absorbent fouling conditions cooperatively rely on multiple parameters: the cooling water temperature, the riser temperature, and the air velocity, with a minimal impact of the particle type. The physical parameters were found to be vitally correlated with another crucial factor: the relative humidity, implying that modulation of the relative humidity would be essential to prevent absorbent fouling in fluidized beds.
Was passiert beim Zusammenstoß zweier Schwarzer Löcher?
Authors: Tkebuchava Giorgi
Published: July 2022

Um diese Fragestellung zu beantworten, muss man sich zunächst mit den physikalischen Grundlagen vertraut machen: Wir beginnen mit Einsteins Relativitätstheorie, befassen uns dann mit den Eigenschaften Schwarzer Löcher, bevor wir zum Zweikörpersystem kommen. Wir betrachten die Kollision zweier Schwarzer Löcher und analysieren, welche physikalischen Größen sich dabei verändern.
Social structures, social change and the metric/nonmetric distinction
Authors: Guy Jean‐Sébastien
Published: July 2022

This paper examines how the concepts of social structure and social change are interpreted in sociological theory today. Social structures are commonly defined in opposition with agency and accordingly as constraints on action. Concomitantly, social change is understood as emancipation or the removal of such constraint through the exercise of agency (and for it). Against this common understanding, the paper develops an alternative approach so as first to articulate a more sophisticated model of social change, one that does not boil to an over‐dramatic opposition between constraint and release from constraint, and second to distinguish between different types of social structures, metric and nonmetric, thereby making room for a variety of social changes depending on how structures interact with other structures.
Ifosfamide‐induced acute kidney injury in a patient with leiomyosarcoma: A case report
Authors: Boskabadi Javad , Yousefi‐Mazhin Ehsan , Salehifar Ebrahim
Published: July 2022

Background

Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma that is derived from smooth muscles. Ifosfamide is in use for advanced metastatic LMS.

Case

A‐44‐years old woman with a chief complaint of pain in the epigastric area, itching, coughing, nausea, and vomiting was referred to the emergency department. Her medical history was LMS. She had taken Ifosfamide and mesna in her last chemotherapy. Seventy percent of her liver and her left kidney were removed 4 years ago to prevent the progress of the disease. Because of the increase in the level of creatinine and urea in the initial laboratory report, a Shaldon catheter was inserted for the patient, and she was under emergency dialysis for 3 h. In addition, during the six‐day hospitalization period, dialysis was done two times. Finally, the patient was discharged with improved clinical tests accompanied by a twice‐weekly dialysis order.

Conclusion

Ifosfamide is metabolized into chloroacetaldehyde, which can cause acute kidney injury. Recovery from acute kidney injury may not always be perfect and can lead to some degree of chronic kidney disease. Opposite to hemorrhagic cystitis, mesna is not effective in preventing ifosfamide's nephrotoxicity and N‐acetylcysteine may be effective in the prevention of this nephrotoxicity.
A novel trust recommendation model in online social networks using soft computing methods
Authors: Sirisala NageswaraRao , Yarava Anitha , Reddy Y. C. A. Padmanabha , Poola Veeresh
Published: July 2022

Social network (OSN) is an emerging platform through which people can connect with their friends, relatives, and other like‐minded people. On the other hand, users' personal information might be misused because of other users' biased and malicious behavior. Establishing a trusted environment in social networks is one of the current research problems. Some of the research papers proposed to trust computational methods, but still, there is a lack of methods to handle biased recommendations and loss of trust accuracy towards the target user. In this article, to address these open issues, “a novel trust recommendation model in online social networks using soft computing methods (TRMSC)” is proposed for the Twitter social networks. Here direct and indirect trust is computed for known and unknown users, respectively. The direct trust of a user is computed using clustering methods based on his social activities (posts, retweets received, mentions received, listed count, and follower count) with other users. In the computation of indirect trust, the impact of biased recommendations is suppressed using the Dempster Shafer theory(DST) method, and loss of trust is minimized using trust transitive matrices. The performance of the proposed method is analyzed theoretically and experimentally. Time and space complexities are measured using asymptotic notations. In experimental results, TRMSC is evaluated for different network sizes and for target users at different distances (2 to 4‐hops), where it could perform better than existing methods.
An arbitrable multi‐replica data auditing scheme based on smart contracts
Authors: Tian Junfeng , Yang Qian
Published: July 2022

In order to improve the availability and persistence of data, lightweight cloud users want to store multiple‐replicas of the original file on the server with less local computing and storage overhead. Meanwhile, to ensure the integrity of the remote storage data, some schemes have been designed to allow public verification. However, most existing schemes only focus on malicious cloud service providers and ignore the possibility that dishonest users cheat for profit. This article implements an arbitrable data auditing scheme under multi‐replica storage. The scheme adopts a new arbitration mechanism under multi‐replica storage, makes use of the non‐tampering characteristics of smart contracts, carries out reliable verification through miners, and realizes the timely detection and punishment of any fraudulent entity. In addition, the scheme also designs a multi‐replica storage model based on the B* tree, realizes the batch verification of replica blocks, enables the fraud behavior of malicious users to be identified after data update, and improves the space utilization efficiency. The article also gives detailed security proof of the proposed scheme. The evaluation result shows our scheme not only realizes a more practical and fairer audit scheme but also has lower computational overhead than current state‐of‐the‐art multi‐replica arbitrable schemes.
CSFPA: An intelligent hybrid workflow scheduling algorithm based upon global and local optimization approach in cloud
Authors: Sharma Gaurav , Khurana Savita , Harnal Shilpi , Lone Showkat Ahmad
Published: July 2022

In cloud, the most prominent area is workflow scheduling due to its widespread application in different domains. It comes under the NP‐complete problem, henceforth researchers have suggested the nature‐inspired heuristics and metaheuristic algorithms but still, the results of these heuristics are not optimal. These algorithms are not competitive but complementary to each other, so in that case, hybridization may yield better results. Since then, researchers have started to combine different heuristics for better results. But in this process of hybridization, the two most important factors have not been considered yet, namely global and local optimization. The proposed work has considered the two most popular nature‐inspired workflow scheduling Cuckoo Search (CS) algorithm and Flower Pollination Algorithm (FPA) for hybridization. CS works best for global optimization, and FPA provides good results in the case of local optimization. The proposed work leveraged the benefits of both optimizations and proposed a novel hybrid algorithm entitled Cuckoo Search Flower Pollination Algorithm (CSFPA). The proposed hybrid algorithm uses multi‐objective functions to minimize cost and time and thus enhance the utilization of resources. The CSFPA algorithm has been compared with both single nature aspired algorithms and hybrid algorithm for performance evaluation.
High‐throughput Method for Novel Medium Development for Culture of Anaerobic Gut Bacteria
Authors: Wornell Kristina , Pardesi Bikiran , Lee Kevin , Boycheva Svetlana , Roberton Anthony M. , White W. Lindsey
Published: July 2022

Gut microbiota play important roles in the health of their host and detailed investigation of these organisms requires in vitro culture. Culturing strictly anaerobic bacteria can be a challenge as the gut environment they inhabit is nutritionally complex. Use of complex media containing nutritionally rich but undefined gut fluid reduces the accuracy of physiological and metabolomic studies. Here we present a high‐throughput protocol for comparing growth rates of fastidiously anaerobic bacteria on different media. These protocols can be used to develop a solid medium made up of commercially sourced ingredients, providing replicable growth conditions for previously uncultured anaerobic bacteria. As many fastidious bacteria grow poorly in a liquid broth, these protocols measure bacterial growth rate on solid media. These protocols speed up and simplify the growth rate measurement process by using a multiwell format and equations in place of physical McFarland standards to calculate approximate cell density. Bacterial strains belonging to the families Erysipelotrichaceae and Lachnospiraceae (phylum Firmicutes) isolated from the hindgut of Kyphosus sydneyanus were used to demonstrate the efficacy of these protocols. Bacterial growth rates were compared between a nutritionally rich medium with gut fluid versus a novel replicable medium with mannitol. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Preparation of solid YCFA growth medium

Basic Protocol 2: Collection of fish gut samples and plating to single isolates

Basic Protocol 3: Genetic identification of single isolates with colony PCR and 16S rRNA gene sequencing

Basic Protocol 4: Measurement of bacterial growth rates on solid media
Receptor Interactome Discovery with RDIMIS, a Membrane Protein Interaction Screen Using Recombinant Extracellular Vesicles
Authors: Sanchez Ariana D. , Peterson Sean M. , Reichelt Mike , Amador Christian M. , Martinez‐Martin Nadia , Cao Shengya
Published: July 2022

Membrane protein interactions are challenging to identify because of the unique biophysical characteristics of both transmembrane proteins and membrane environments. The Receptor Display in Membranes Interaction Screen (RDIMIS) platform overcomes these challenges by screening transmembrane and membrane‐proximal proteins in a membrane environment using recombinant extracellular vesicles (rEVs). The screen has been used to successfully identify interactions for difficult‐to‐study receptors in an unbiased manner. In this report, we detail how we generate rEVs, characterize the rEVs to ensure screen‐readiness, and perform the full interaction screening, with emphasis on the criteria necessary to obtain clear, interpretable results. We also include support protocols for generating a screening library and validating screening results, as well as an alternate protocol for RDIMIS enabling the profiling of naturally occurring extracellular vesicles. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Generating and isolating extracellular vesicles from cells

Basic Protocol 2: Characterizing recombinant extracellular vesicles

Support Protocol 1: Preparing the receptor screening library

Basic Protocol 3: Performing the Receptor Display in Membranes Interaction Screen (RDIMIS)

Support Protocol 2: Validating RDIMIS results using microscopy

Alternate Protocol: Detecting unlabeled endogenous vesicles
DNA barcoding, multilocus phylogeny, and morphometry reveal phenotypic plasticity in the Chinese freshwater mussel Lamprotula caveata (Bivalvia: Unionidae)
Authors: Wu Ruiwen , Liu Xiongjun , Guo Liang , Zhou Chunhua , Ouyang Shan , Wu Xiaoping
Published: July 2022

Accurate species identification is crucial for developing conservation strategies for freshwater mussels, one of the most imperiled faunas in the world. Traditionally, mussel species description primarily relied on conchological characters. However, shell morphology has great variability, which leads to the complexity of species delimitation. As endemic species to China, Lamprotula caveata was originally described by Heude (1877). Lamprotula quadrangulosus and Lamprotula contritus were considered for synonymization of L. caveata based on shell variants in the early 20th century, which has been long debated due to lack of rigorous molecular analysis. Moreover, great morphological variation caused doubt whether there are cryptic species. In this study, we used a combined phylogenetic and morphometric approach to verify the validity of the synonymization of L. caveata. The results of molecular species delimitation showed that two molecular operational taxonomic units (MOTUs) were identified in Lamprotula spp., including the L. leaii lineage and the complex lineage (L. quadrangulosa, L. cornuumlunae, L. contritus, and L. caveata). Phylogenetic analyses revealed that L. cornuumlunae formed a basal monophyletic clade, whose divergence time was relatively recent (4.26 Ma [95% HPD = 1.91–7.22 Ma]), and L. contritus, L. caveata, and L. quadrangulosa formed a large polytomy group with very shallow branches. In the previous study, we have demonstrated the validity of L. cornuumlunae. The molecular evidences supported that the complex (L. quadrangulosa + L. contritus + L. caveata) was a valid species; L. quadrangulosa and L. contritus were synonyms of L. caveata. In addition, three morphospecies (L. quadrangulosa, L. contritus, and L. caveata) were aggregated without clear differentiation based on shell morphometric analysis. We confirmed multiple phenotypes in L. caveata for species identification and presumed that the phenotypic plasticity was a response to specific habitats. This study clarified the diversity and phylogeny of the Lamprotula group, which is a crucial step for developing new conservation and management strategies for this imperiled group.
Assessing scale‐dependent effects on Forest biomass productivity based on machine learning
Authors: He Jingyuan , Fan Chunyu , Geng Yan , Zhang Chunyu , Zhao Xiuhai , Gadow Klaus von
Published: July 2022

Estimating forest above‐ground biomass (AGB) productivity constitutes one of the most fundamental topics in forest ecological research. Based on a 30‐ha permanent field plot in Northeastern China, we modeled AGB productivity as output, and topography, species diversity, stand structure, and a stand density variable as input across a series of area scales using the Random Forest (RF) algorithm. As the grain size increased from 10 to 200 m, we found that the relative importance of explanatory variables that drove the variation of biomass productivity varied a lot, and the model accuracy was gradually improved. The minimum sampling area for biomass productivity modeling in this region was 140 × 140 m. Our study shows that the relationship of topography, species diversity, stand structure, and stand density variables with biomass productivity modeled using the RF algorithm changes when moving from scales typical of forest surveys (10 m) to larger scales (200 m) within a controlled methodology. These results should be of considerable interest to scientists concerned with forest assessment.
Emergence activity at hibernacula differs among four bat species affected by white‐nose syndrome
Authors: Jackson Reilly T. , Willcox Emma V. , Zobel John M. , Bernard Riley F.
Published: July 2022

Prior to the introduction of white‐nose syndrome (WNS) to North America, temperate bats were thought to remain within hibernacula throughout most of the winter. However, recent research has shown that bats in the southeastern United States emerge regularly from hibernation and are active on the landscape, regardless of their WNS status. The relationship between winter activity and susceptibility to WNS has yet to be explored but warrants attention, as it may enable managers to implement targeted management for WNS‐affected species. We investigated this relationship by implanting 1346 passive integrated transponder (PIT) tags in four species that vary in their susceptibility to WNS. Based on PIT‐tag detections, three species entered hibernation from late October to early November. Bats were active at hibernacula entrances on days when midpoint temperatures ranged from −1.94 to 22.78°C (mean midpoint temperature = 8.70 ± 0.33°C). Eastern small‐footed bats (Myotis leibii), a species with low susceptibility to WNS, were active throughout winter, with a significant decrease in activity in mid‐hibernation (December 16 to February 15). Tricolored bats (Perimyotis subflavus), a species that is highly susceptible to WNS, exhibited an increase in activity beginning in mid‐hibernation and extending through late hibernation (February 16 to March 31). Indiana bats (M. sodalis), a species determined to have a medium–high susceptibility to WNS, remained on the landscape into early hibernation (November 1 to December 15), after which we did not record any again until the latter portion of mid‐hibernation. Finally, gray bats (M. grisescens), another species with low susceptibility to WNS, maintained low but regular levels of activity throughout winter. Given these results, we determined that emergence activity from hibernacula during winter is highly variable among bat species and our data will assist wildlife managers to make informed decisions regarding the timing of implementation of species‐specific conservation actions.
The role of knowledge in supporting the revitalisation of traditional landscape governance through social innovation in Slovakia
Authors: Špaček Martin , Melnykovych Mariana , Kozová Mária , Pauditšová Eva , Kluvánková Tatiana
Published: July 2022

In this paper, we determine the role of knowledge in the development and consolidation of social innovation (SI) on the revitalisation of traditional farming in marginalised rural settings. We seek to address the following questions: (i) how the co‐production of knowledge in SI initiatives for the revitalisation of traditional farming might influence its development path, and (ii) how the networking of local and external actors accelerates knowledge co‐production and triggers the reconfiguration of social practices towards sustainability transformation. To answer these questions, we applied mixed‐method approach by investigating the example of SI initiative (the case of Vlkolínec UNESCO site in Slovakia). We conducted a focus group, semi‐structured and structured interviews, historical analysis and social network analysis with the actors involved in the SI. Based on the empirical results we revealed how mix of local and external knowledge and knowledge co‐production can enhance the development of SI through the networking of numerous local stakeholders, particularly science and policy representatives. This knowledge sharing and knowledge co‐production strengthened the development path of the SI in seeking to initiate effective measures for local people to return to traditional small‐scale farming, supporting traditional crafts, creating new green jobs and conditions for improving the quality of life for local people, and new services for sustainable tourism. Our results highlight the importance of external knowledge in the expansion of bonding social capital, and the establishment of a regional knowledge network of local and external actors to trigger SI in rural areas. The analyses reveal that multi‐actor networks that support knowledge exchange play an important role in SI development paths.
In Celebration of the 65th Birthday of Rinaldo Poli
Authors: Fliedel Christophe , Guillo Pascal , Manoury Eric
Published: July 2022

Rinaldo Poli's significant contribution to coordination chemistry, catalysis and computational chemistry has been benefitting scientific communities for decades. In addition, Rinaldo Poli has been providing valuable support to many chemistry societies and journals. This special collection presents about 30 excellent research articles and reviews in celebration of Rinaldo Poli's 65th birthday.
Studies towards the Total Synthesis of Amycolamicin: A Chiral Auxiliary‐Based Diels‐Alder Approach towards the Decalin Core
Authors: Frossard Thomas M. , Trapp Nils , Altmann Karl‐Heinz
Published: July 2022

The stereoselective synthesis of (1S,2S,5R)‐5‐((4‐methoxybenzyl)oxy)‐2‐methyl‐8‐methylene‐1,2,4a,5,6,7,8,8a‐octahy‐dronaphthalene‐1‐carboxylic acid (2) is described, which comprises the bicyclic core structure of the natural product amycolamicin (1). The bicyclic ring‐system was established via an intramolecular Diels‐Alder reaction of a triene carrying a SuperQuat chiral auxiliary. The latter could be readily removed by methanolysis in excellent yield, which allowed for effective conversion of a hydroxy group at C(1) into the methylene group present in the natural product. The intramolecular Diels‐Alder reaction could also be performed with a triene incorporating a classical, phenylalanine‐derived Evans auxiliary, but the removal of the latter from the initial Diels‐Alder product was hampered by competing attack of nucleophiles on the endocyclic carbonyl group in the oxazolidinone ring. Acid 2 could be converted into an acyl cyanide that features as a key advanced intermediate in one of the three total syntheses of amycolamicin reported to date.
Experimental assessment for the thermal performance of scrap tire blocks as external wall insulators
Authors: Hashem Alaa Liaq , Farhood Husam Jasim
Published: July 2022

In this article, the advantage of reusing scrap tires in scrap rubber block (SRB) to improve thermal insulation in buildings was examined experimentally. By testing the use of SRB in black and white colors as external wall insulators and comparing their performance with walls without insulation. The results indicated that a wall with scrap tire blocks gave the best thermal insulation results when the outer face was painted white. The decrement factor () and the rate of heat loss increase, while the rate of heat gain decreases. This was done through the mechanisms of heat transfer by conduction through the layers of the wall and the effect of adding the rubber block on its thermal properties. The results showed that the use of rubber blocks reduces the temperature of the inner surface of the wall by 3–4°C lower than the traditional wall. The thermal diffusion inside the wall was determined effectively in the case of a wall with the rubber block, where the temperature of the inner surface reaches its maximum value by about 0.5‐h difference from the traditional wall in the case of the wall with the rubber block in black color, and 9.5‐h in the case with the white block.
The impact of COVID‐related economic shocks on household mental health in Pakistan
Authors: Baranov Victoria , Grosjean Pauline , Khan Fatima Jamal , Walker Sarah
Published: July 2022

We combine data collected just prior to the unfolding of COVID‐19 with follow‐up data from July 2020 to document the adverse economic effects of the pandemic and resulting impact on parental and child mental well‐being in peri‐urban Pakistan. 22% of the households in our sample are affected by job loss, with monthly income down 38% on average. Our difference‐in‐difference results show that job loss is associated with a 0.88 standard deviation (SD) increase in adult mental distress scores (K10), a 0.43 SD reduction in a Hope index of children's aspirations, agency and future pathways, and a 0.39 SD increase in children's depression symptoms. In addition, we observe higher levels of parental stress and anger reported by children, as well as an increase in reported prevalence of domestic violence. Overall, we document that the pandemic has disproportionately and negatively affected the economic and mental well‐being of the most vulnerable households in our sample.
Survival and prognosis of metastatic head and neck adenoid cystic carcinoma
Authors: Zhang Di , Chai Yue , Wei Yuce , Qi Fei , Dong Mei
Published: July 2022

Background

To investigate the clinical characteristics, treatment, and prognosis of patients with metastatic head and neck adenoid cystic carcinoma (HNACC).

Method

The clinical data of metastatic HNACC from 1999 to 2020 at the National Cancer Center of China were retrospectively collected.

Results

One hundred seventy‐four patients with metastatic HNACC were enrolled and median overall survival (OS) was 45.6 months. Univariate analysis indicated that smoking history, disease‐free interval (DFI), number and sites of metastases, and systemic therapy were associated with OS. In the multivariate analysis, non‐smokers, DFI ≥3 years, and lung metastasis were prognostic factors. Local therapy for localized disease could prolong survival in patients with both recurrent and metastatic disease.

Conclusion

No smoking history, DFI ≥3 years, and lung metastasis were favorable prognostic factors. Local therapy for metastases could not provide survival benefits, but local therapy for localized disease may prolong survival. Whether initial systemic therapy could improve prognosis needs further exploration.
In vivo imaging of calcium dynamics in zebrafish hepatocytes
Authors: Pozo‐Morales Macarena , Garteizgogeascoa Inés , Perazzolo Camille , So Juhoon , Shin Donghun , Singh Sumeet Pal
Published: July 2022

Background and Aims:

Hepatocytes were the first cell type for which oscillations of cytoplasmic calcium levels in response to hormones were described. Since then, investigation of calcium dynamics in liver explants and culture has greatly increased our understanding of calcium signaling. A bottleneck, however, exists in observing calcium dynamics in a noninvasive manner because of the optical inaccessibility of the mammalian liver. Here, we aimed to take advantage of the transparency of the zebrafish larvae to image hepatocyte calcium dynamics in vivo at cellular resolution.

Approach and Results:

We developed a transgenic model expressing a calcium sensor, GCaMP6s, specifically in zebrafish hepatocytes. Using this, we provide a quantitative assessment of intracellular calcium dynamics during multiple contexts, including growth, feeding, ethanol‐induced stress, and cell ablation. Specifically, we show that synchronized calcium oscillations are present in vivo, which are lost upon starvation. Starvation induces lipid accumulation in the liver. Feeding recommences calcium waves in the liver, but in a spatially restricted manner, as well as resolves starvation‐induced hepatic steatosis. By using a genetically encoded scavenger for calcium, we show that dampening of calcium signaling accelerates the accumulation of starvation‐related lipid droplets in the liver. Furthermore, ethanol treatment, as well as cell ablation, induces calcium flux, but with different dynamics. The former causes asynchronous calcium oscillations, whereas the latter leads to a single calcium spike.

Conclusions:

We demonstrate the presence of oscillations, waves, and spikes in vivo. Calcium waves are present in response to nutrition and negatively regulate starvation‐induced accumulation of lipid droplets.
High‐resolution temporal dynamics of intra‐storm isotopic composition of stemflow and throughfall in a Mediterranean Scots pine forest
Authors: Pinos Juan , Llorens Pilar , Latron Jérôme
Published: July 2022

Vegetation plays a significant role in the isotopic fractionation of rainwater during rainfall partitioning through the canopy into throughfall and stemflow. Most studies focus on the isotopic composition of throughfall, whereas that of stemflow has been studied much less frequently. Moreover, only three studies to date have investigated stemflow isotopic composition at the intra‐storm scale. Therefore, knowledge of the isotopic shift between rainfall and throughfall/stemflow at fine resolutions is sorely needed in order to better understand water input to forest soils. In this study, intra‐event rainfall, throughfall and stemflow in a Scots pine forest under Mediterranean conditions were monitored (5‐min time step) over a 20‐month period (May 2018 to December 2019) and water samples of each component were collected sequentially by means of automatic samplers for isotopic analysis (18O and 2H). Results obtained for 21 rainfall events show that throughfall was usually more enriched than rainfall and stemflow was more enriched than throughfall. Isotopic differences between rainfall and throughfall/stemflow indicated that throughfall was more depleted during the higher air temperature season whereas stemflow was more enriched. The isotopic shift did not show any direct relationship with either meteorological variables or the amount effect. At the intra‐storm scale, stemflow was more enriched than rainfall and throughfall at the start of the rainfall event and tended to decrease towards the end. Our results suggest that evaporation led to stemflow enrichment due to stemflow residing longer on the vegetative surfaces than throughfall. However, most fractionation factors can occur during the same event. Our study will improve understanding of the physical processes that control stemflow isotopic composition in coniferous trees before reaching the ground, as a step towards improving isotope‐based models for forest‐water interactions.
Does R&D investment drive employment growth? Empirical evidence at industry level from Japan
Authors: Shah Imran Hussain , Kollydas Konstantinos , Lee Pak Yee , Malki Issam , Chu Crystal
Published: July 2022

Strong demographic headwinds have motivated Japan to strengthen its economy by fostering innovation. This paper draws on a panel of business enterprises operating in 33 industries in Japan to examine how research and development (R&D) activities affect employment. Our findings suggest that employment gains are associated with innovation, both at the aggregate level and within groups of major industries. The positive impact of technological advancement is more pronounced in the manufacturing sector. The results reveal heterogeneous patterns of the key determinants of employment growth based on the level of industries' routine intensity, but they accord well with the compensation theory concerning the connection between innovation and job creation. These results will be of interest for policymakers to design targeted economic strategies by supporting technological development in Japan and could also serve as a compass for other countries with similar workforce structures and macroeconomic characteristics.
Novel therapeutic modalities target cell signaling of Renin‐Angiotensin system/NF‐κB‐induced cell cycle arrest and apoptosis in urethane‐induced lung cancer in mice: An in vivo study
Authors: Khalaf Marwa M. , Abo‐Youssef Amira M. , Malak Marina N. , Hamzawy Mohamed A.
Published: July 2022

Background

Lung cancer has risen to the top of the list of cancer‐related deaths worldwide. Aliskiren is a direct renin inhibitor.

Aim

This study aims to investigate the impact of cell signaling of Renin‐Angiotensin system (RAS)/NF‐κB on lung cancer by investigating the potential therapeutic effects of aliskiren for lung cancer treatment in urethane‐induced lung cancer in mice.

Methods

Male BALB/c mice were randomly assigned to one of five treatment groups for 150 days, including (1) normal control; (2) aliskiren (25 mg/kg/i.p) daily, (3) urethane at a dose of 1.5 g/kg (i.p) at Day 1 and 60 (nonsmall cell lung cancer[NSCLC] group) (4) NSCLC mice received carboplatin (15 mg/kg/i.p) every other day for the last 4 successive weeks and (5) NSCLC mice treated with aliskiren daily. Tumor size was determined based on blood sampling, and lungs were isolated for biochemical analysis, western blot analysis assay, and histopathological examination.

Results

Urethane demonstrated significant changes in all biochemical and molecular parameters and histological patterns. Aliskiren‐treated mice had significantly lower levels of NF‐κB p65, Bcl‐2, cyclin D1, ICAM‐1, MMP‐2, and Nrf2, with an increase in the catalytic activity of caspase‐3 due to its RAS inhibitory mechanism. The combined urethane administration with aliskiren demonstrated a significant improvement in the histopathological examination.

Conclusion

RAS/NF‐B cell signaling is a potential therapeutic target for preventing and treating lung adenocarcinoma, evidenced by the fundamental cytotoxic mechanism and attenuation of metastasis and angiogenesis induced by the treatment of NSCLC mice with aliskiren.