bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and characterization of two new mixed‐ligand Cu(II) complexes of a tridentate NN'O type Schiff base ligand and N‐donor heterocyclic co‐ligands: In vitro anticancer assay, DNA/human leukemia/COVID‐19 molecular docking studies, and pharmacophore modeling
Authors: Ghasemi Liana , Behzad Mahdi , Khaleghian Ali , Abbasi Alireza , Abedi Anita
Published: February 2022

Two new mixed‐ligand complexes with general formula [Cu(SB)(L')]ClO4 (1 and 2) were synthesized and characterized by different spectroscopic and analytical techniques including Fourier transform infrared (FT‐IR) and UV–Vis spectroscopy and elemental analyses. The SB ligand is an unsymmetrical tridentate NN'O type Schiff base ligand that was derived from the condensation of 1,2‐ethylenediamine and 5‐bromo‐2‐hydroxy‐3‐nitrobenzaldehyde. The L' ligand is pyridine in (1) and 2,2′‐dimethyl‐4,4′‐bithiazole (BTZ) in (2). Crystal structure of (2) was also obtained. The two complexes were used as anticancer agents against leukemia cancer cell line HL‐60 and showed considerable anticancer activity. The anticancer activity of these complexes was comparable with the standard drug 5‐fluorouracil (5‐FU). Molecular docking and pharmacophore studies were also performed on DNA (PDB:1BNA) and leukemia inhibitor factor (LIF) (PDB:1EMR) to further investigate the anticancer and anti‐COVID activity of these complexes. The molecular docking results against DNA revealed that (1) preferentially binds to the major groove of DNA receptor whereas (2) binds to the minor groove. Complex (2) performed better with 1EMR. The experimental and theoretical results showed good correlation. Molecular docking and pharmacophore studies were also applied to study the interactions between the synthesized complexes and SARS‐CoV‐2 virus receptor protein (PDB ID:6LU7). The results revealed that complex (2) had better interaction than (1), the free ligands (SB and BTZ), and the standard drug favipiravir.
Human urinary kallidinogenase may improve the prognosis of acute stroke patients with early neurological deterioration
Authors: Xie Yiju , Li Shengyu , Zhang Jian , Chen Shijian , Deng Xuhui , Cen Gengyu , Liang Zhijian
Published: February 2022

Objectives

Some acute ischemic stroke (AIS) patients still suffer from early neurological deterioration (END) after receiving intravenous thrombolysis (IVT), and these patients often have a poor prognosis. The purpose of our study is to observe the efficacy and safety of human urinary kallidinogenase (HUK) treatment in patients with END.

Methods

This was a retrospective analysis and 49 patients with END who met the inclusion criteria were divided into the observation group and the control group. All patients received routine treatment of AIS, while patients in the observation group were treated with HUK within 24 h after IVT and the other group without HUK.

Results

There were 24 patients in the observation group and 25 patients in the control group. After treatment, favorable prognosis (mRS scores ≤2) at 3 months in the observation group with 13 cases (54.17%) was significantly better than that in the control group with four cases (16%) (p = .001), and there was no statistical difference between the two groups in any hemorrhagic complication.

Conclusion

HUK is considered to be safe and may improve the prognosis of AIS patients with END after IVT. More clinical trials are needed to validate these results in the future.
Identification of prognostic biomarkers for papillary thyroid carcinoma by a weighted gene co‐expression network analysis
Authors: Meng Kexin , Hu Xiaotian , Zheng Guowan , Qian Chenhong , Xin Ying , Guo Haiwei , He Ru , Ge Minghua , Xu Jiajie
Published: February 2022

Aim

Whole transcriptome analysis was conducted to identify differentially expressed RNAs and regulatory networks associated with papillary thyroid carcinoma (PTC).

Methods

A weighted gene co‐expression network analysis based on high‐throughput sequencing data for six pairs of PTC and adjacent tissue samples was conducted to understand the biological functions and regulatory networks involving long non‐coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs).

Results

We detected 131, 338, 31, and 556 differentially expressed circRNAs, lncRNAs, miRNAs, and mRNAs, respectively. We identified modules that were significantly positively and negatively related to cancer and lymph node metastasis. Gray and turquoise modules were positively correlated with cancer phenotypes (p < 0.05), whereas yellow, brown, and blue modules were negatively correlated with cancer (p < 0.05). Gray module was positively correlated with lateral lymph node metastasis (p = 0.02). Kaplan–Meier analyses revealed that the levels of transmembrane protein 63C (TMEM63C), lysyl oxidase‐like 1 (LOXL1), collagen type V alpha 1 chain (COL5A1), ADAM metalloproteinase with thrombospondin type I motif 2 (ADAMTS2), and LysM‐domain containing 3 (LYSMD3) were significantly associated with overall survival (p < 0.05). Significant increase in the expression ofCOL5A1andLOXL1in tumor tissues was validated by quantitative real‐time polymerase chain reaction (p < 0.05).COL5A1andLOXL1promoted PTC cell growth and invasion in vitro.

Conclusions

We identifiedCOL5A1andLOXL1as potential prognostic biomarkers, providing new insights into the occurrence and progression of PTC.
Neonatal intestinal diffuse ganglioneuromatosis with plexiform neurofibromas; Diagnostic and management pitfalls—A case report
Authors: Essa Madani
Published: February 2022

Neonatal intestinal ganglioneuroma and neurofibromatosis are rare in neonates. It is a challenging pathology to diagnose and treat. A 3‐week‐old full‐term newborn with a birth weight of 3.5 kg of Arabic ethnicity presented to the emergency department with a recurrent refractory intestinal obstruction. The patient has been diagnosed initially with intestinal obstruction secondary to malrotation and then operated again because of adhesion and internal herniation. Finally, after the third laparotomy, the patient was diagnosed with intestinal ganglioneuromatosis and neurofibromatosis. We reviewed the literature on the diagnosis and management of this rare pathology among neonates and to increase the awareness of it. Intestinal ganglioneuromatosis is a rare neonatal pathology. The clinical presentation of intestinal ganglioneuromatosis is similar to that of intestinal obstructions caused by many other diseases. Ganglioneuromatosis is differentiated from other differential diagnoses based on histopathology. Early diagnosis is vital to ensure appropriate management.
Usefulness of position emission tomography/computed tomography in a case of sarcoidosis with multiorgan involvement
Authors: Amano Norihiko , Takahashi Soshi , Hatachi Saori , Kumagai Shunichi
Published: February 2022

Sarcoidosis, a systemic inflammatory disease of unknown etiology, can affect any site in the body. A bone lesion was unexpectedly detected by fluorodeoxyglucose position emission tomography/computed tomography (FDG PET/CT) in a patient with multiorgan sarcoidosis. FDG PET/CT should be considered for the detection of clinically silent lesions of sarcoidosis.
Cutaneous leishmaniasis: A case report of a diagnostic dilemma
Authors: Pudasaini Prajwal , Pudasaini Prashanta
Published: February 2022

Cutaneous leishmaniasis (CL) is the most prevalent clinical form of leishmaniasis and is caused by vector‐borne protozoan parasite. Variation in diagnostic accuracy exists. A 54‐year‐old female farmer by occupation presented with lesion over right thigh for 8 months. Lesion evolved over period of 2–3 months and progressed to form ulcer with surrounding redness. On examination, solitary plaque with crateriform ulcer 3 * 2 cm in size roughly oval in shape was present. Ulcer floor was moist, smooth shiny with serous discharge, and well‐defined raised erythematous margin was present. Biopsy was done which showed features suggestive of lupus vulgaris, for which anti‐tubercular treatment (ATT) was started. There was persistence of ulcer despite 4 months of ATT, for which diagnosis was reconsidered and fine‐needle aspiration cytology (FNAC) was performed. FNAC showed numerous intra‐ and extracellular amastigotes suggestive of leishmaniasis which was treated with complete disappearance of ulcer over 4 months.
Atypical localization of demodicosis after COVID‐19 infection
Authors: Lahouel Ines , Said El Mabrouk Randa , Hadhri Rim , Youssef Monia , Belhadjali Hichem , Zili Jameleddin
Published: February 2022

Since its outbreak in December 2019, a consistent number of case reports have been published describing a complex spectrum of skin manifestations associated with COVID‐19. We report a first observation of demodicosis of the scalp after a severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2) infection.
Spindle cell lipoma: An uncommon variant of lipoma affecting the foot sole
Authors: Ben Salah Nesrine , Lahouel Ines , Manaa Linda , Youssef Monia , Belhadjali Hichem , Zili Jameleddine
Published: February 2022

We report a 36‐year‐old male with an atypical variant of lipoma occurring on an atypical site.
Robot‐assisted excision of rectal duplication cysts: A case report
Authors: Kitazono Masaki , Fujita Makoto , Oyama Tomohiro , Ikeda Naotaka , Eguchi Mayumi , Kamimura Go , Sato Rikiya , Uchiyama Shuichiro , Toyosaki Ryoichi , Suenaga Toyokuni , Shimaoka Shunji
Published: February 2022

Rectal duplication cysts are extremely rare and account for only 4% of all gastrointestinal duplication cysts. They may become challenging for removal in the case of a large tumor in a narrow pelvis. Herein, we report a case of rectal duplication cysts excision via robotic‐assisted laparoscopic surgery and its utility.
Kaposiform hemangioendothelioma with fatal income: Kasabach–Merritt phenomenon and hypercalcemia
Authors: Massara Baklouti , Mariem Rekik , Emna Bahloul , Meriam Triki , Faiza Safi , Sonia Boudaya , Meriem Amouri , Lamia Gargouri , Tahia Sellami , Hamida Turki
Published: February 2022

Kaposiform hemangioendothelioma is a rare, borderline tumor that typically occurs during early childhood. Kasabach–Merritt phenomenon is a complication characterized by a consumptive coagulopathy resulting from the localized intravascular coagulation. Hypercalcemia generation is a rare association that was related in our case to parathyroid hormone‐related protein produced by this angioma.
Distributed process monitoring for large‐scale processes based on MJMI‐weighted DKPCA
Authors: Zhang Qi , Li Peng , Lang Xun , Miao Aimin , Xie Lei
Published: February 2022

Although the distributed monitoring model has been widely employed in monitoring large‐scale processes, the dynamic nonlinear property in process data is rarely investigated. Given the complex dynamic nature of industrial processes, different process variables interact with each other over time. In order to describe the correlation of dynamic variables more accurately, this work proposes a novel dynamic nonlinear fault detection framework based on maximum joint mutual information (MJMI)‐weighted dynamic kernel principal component analysis (WDKPCA). After dividing the process variables using the MJMI scheme, the proposed dynamic weighting method defines the weight of time‐delayed variables, which allows the dynamic characteristics of these variables to be characterized more comprehensively. By these means, the processes can be decomposed into multiple subblocks, and a distributed monitoring scheme based on DKPCA is thus established. Then, the Bayesian fusion strategy is used to fuse the monitoring results of different subblocks. Through a series of experiments on the Tennessee Eastman (TE) process, the results indicate that MJMI‐WDKPCA has superior process monitoring performance.
Digital reconstruction and quantitative morphometric analysis of bipolar cells in live rat retinal slices
Authors: Fournel Rémi , Veruki Margaret L. , Hartveit Espen
Published: February 2022

Bipolar cells convey signals from photoreceptors in the outer retina to amacrine and ganglion cells in the inner retina. In mammals, there are typically 10–15 types of cone bipolar cells and one type of rod bipolar cell. Different types of cone bipolar cells are thought to code and transmit different features of a complex visual stimulus, thereby generating parallel channels that uniquely filter and transform the photoreceptor outputs. Differential synaptic connectivity and expression of ligand‐ and voltage‐gated ion channels are thought to be important mechanisms for processing and filtering visual signals. Whereas the biophysical basis for such mechanisms has been investigated more extensively in rat retina, there is a lack of quantitative morphological data necessary for advancing the structure–function correlation in this species, as recent connectomics investigations have focused on mouse retina. Here, we performed whole‐cell recordings from cone and rod bipolar cells in rat retinal slices, filled the cells with fluorescent dyes, and acquired image stacks by multiphoton excitation microscopy. Following deconvolution, we performed digital reconstruction and morphometric analysis of 25 cone and 14 rod bipolar cells. Compared to previous descriptions, the extent and complexity of branching of the axon terminal was surprisingly high. By precisely quantifying the level of stratification of the axon terminals in the inner plexiform layer, we have generated a reference system for reliable classification of individual cells in future studies focused on correlating physiological and morphological properties. The implemented workflow can be extended to the development of morphologically realistic compartmental models for these neurons.
Visible‐Light‐Triggered Degradation of pH‐Responsive Micelles Based on ortho‐Hydroxy Cinnamates
Authors: Abramov Alex , Bonardd Sebastián , Saldías César , Díaz Díaz David
Published: February 2022

Micelles made by connecting hydrophobic and hydrophilic chains via photo‐responsive ortho‐hydroxy cinnamate (oHC) units undergo complete degradation within 10 min under visible light irradiation at basic pH values. This proof of concept relies on the controlled cyclization of the oHC moiety affording the corresponding coumarin with the concomitant separation of the hydrophobic portion. Furthermore, the neat polymeric micelles are stable under daylight conditions, thus allowing its storage without special precautions at neutral pH. The amphiphilic nature of mPEG750‐oHC‐dodecyl, expressed as the ability to self‐assemble into micellar aggregates in aqueous media, was corroborated by the measurement of its critical micellar concentration (CMC) by fluorescence analysis, as well as the successful visualization of these aggregates using transmission electron microscopy (TEM). Moreover, the size distribution and suspension stability of these aggregates obtained at different pH values was analyzed in terms of dynamic light scattering (DLS) and zeta potential measurements.
Evaluating Impacts of 4R Nutrient Stewardship
Authors: Bruulsema Tom
Published: February 2022

Nutrients are essential for plant and animal agriculture and comprise a large portion of its outputs. The starting point for assuring beneficial impacts is the adaptive management built into 4R Nutrient Stewardship. To manage adaptively means to evaluate impacts in your decision cycle. The metrics you evaluate need to reflect impacts important to your local farming system. Farther‐reaching impacts of crop nutrition include water quality, air quality, carbon footprint, biodiversity, food security, human nutrition, farm livelihoods, and circularity. By better documenting the decision cycle, our current and past practices, and their relation to impacts, the industry has the opportunity to build public trust. Earn 0.5 CEUs in Nutrient Management by reading this article and taking the quiz at https://bit.ly/3KYONvh. View all CEUs online at https://web.sciencesocieties.org/Learning‐Center/Courses.
Reconstructing lake bottom water temperatures and their seasonal variability in the Dead Sea Basin during MIS5e
Authors: Brall Niels S. , Gardien Véronique , Ariztegui Daniel , Sorrel Philippe , Guillerm Emmanuel , Caupin Frédéric
Published: February 2022

Interglacial periods are characterised by thick accumulations of halite units in the Dead Sea Basin. During these intervals, small water droplets (fluid inclusions, FIs) were entrapped in the halite crystals which serve as windows to estimate the chemistry and physical properties of the primary lake water conditions. Brillouin spectroscopy is used here to reconstruct annual resolution temperatures from a halite core section in the Dead Sea Basin during the onset of Marine Isotope Stage 5e (ca 130 ka) of the Last Interglacial. Lake bottom temperatures can be inferred based on the occurrence of coarse/fine halite facies, as observed today with the formation of equivalent halite facies during winter/summer seasons in the Dead Sea. A recurring increase in lake bottom temperatures is found along the direction of coarse halite layers in three successive years. Moreover, low FI entrapment temperatures were detected in layers of fine (cumulate) halite facies. These results imply a twofold stronger seasonality in the Dead Sea Basin compared to today, with colder winters at the onset of Marine Isotope Stage 5e. The results therefore highlight the potential of using cyclic salt deposits to reconstruct seasonal temperature variability for numerous evaporitic environments in the geological record.
Adaptation to a bacterial pathogen in Drosophila melanogaster is not aided by sexual selection
Authors: Sharda Sakshi , Kawecki Tadeusz J. , Hollis Brian
Published: February 2022

Theory predicts that sexual selection should aid adaptation to novel environments, but empirical support for this idea is limited. Pathogens are a major driver of host evolution and, unlike abiotic selection pressures, undergo epidemiological and co‐evolutionary cycles with the host involving adaptation and counteradaptation. Because of this, populations harbor ample genetic variation underlying immunity and the opportunity for sexual selection based on condition‐dependent “good genes” is expected to be large. In this study, we evolved populations of Drosophila melanogaster in a 2‐way factorial design manipulating sexual selection and pathogen presence, using a gram‐negative insect pathogen Pseudomonas entomophila, for 14 generations. We then examined how the presence of sexual selection and the pathogen, as well as any potential interaction, affected the evolution of pathogen resistance. We found increased resistance to P. entomophila in populations that evolved under pathogen pressure, driven primarily by increased female survival after infection despite selection for resistance acting only on males over the course of experimental evolution. This result suggests that the genetic basis of resistance is in part shared between the sexes. We did not find any evidence of sexual selection aiding adaptation to pathogen, however, a finding contrary to the predictions of “good genes” theory. Our results therefore provide no support for a role for sexual selection in the evolution of immunity in this experimental system.
Drivers of Collembola assemblages along an altitudinal gradient in northeast China
Authors: Xie Zhijing , Sun Xin , Lux Johannes , Chen Ting‐Wen , Potapov Mikhail , Wu Donghui , Scheu Stefan
Published: February 2022

Altitudinal changes in the diversity of plants and animals have been well documented; however, soil animals received little attention in this context and it is unclear whether their diversity follows general altitudinal distribution patterns. Changbai Mountain is one of few well‐conserved mountain regions comprising natural ecosystems on the Eurasian continent. Here, we present a comprehensive analysis of the diversity and community composition of Collembola along ten altitudinal sites representing five vegetation types from forest to alpine tundra. Among 7834 Collembola individuals, 84 morphospecies were identified. Species richness varied marginally significant with altitude and generally followed a unimodal relationship with altitude. By contrast, the density of Collembola did not change in a consistent way with altitude. Collembola communities changed gradually with altitude, with local habitat‐related factors (soil and litter carbon‐to‐nitrogen ratio, litter carbon content, and soil pH) and climatic variables (precipitation seasonality) identified as major drivers of changes in Collembola community composition. Notably, local habitat‐related factors explained more variation in Collembola assemblages than climatic variables. The results suggest that local habitat‐related factors including precipitation and temperature are the main drivers of changes in Collembola communities with altitude. Specifically, soil and litter carbon‐to‐nitrogen ratio correlated positively with Collembola communities at high altitudes, whereas soil pH correlated positively at low altitudes. This documents that altitudinal gradients provide unique opportunities for identifying factors driving the community composition of not only above‐ but also belowground invertebrates.
Low‐pH seawater alters indirect interactions in rocky‐shore tidepools
Authors: Jellison Brittany M. , Elsmore Kristen E. , Miller Jeffrey T. , Ng Gabriel , Ninokawa Aaron T. , Hill Tessa M. , Gaylord Brian
Published: February 2022

Ocean acidification is expected to degrade marine ecosystems, yet most studies focus on organismal‐level impacts rather than ecological perturbations. Field studies are especially sparse, particularly ones examining shifts in direct and indirect consumer interactions. Here we address such connections within tidepool communities of rocky shores, focusing on a three‐level food web involving the keystone sea star predator, Pisaster ochraceus, a common herbivorous snail, Tegula funebralis, and a macroalgal basal resource, Macrocystis pyrifera. We demonstrate that during nighttime low tides, experimentally manipulated declines in seawater pH suppress the anti‐predator behavior of snails, bolstering their grazing, and diminishing the top‐down influence of predators on basal resources. This attenuation of top‐down control is absent in pools maintained experimentally at higher pH. These findings suggest that as ocean acidification proceeds, shifts of behaviorally mediated links in food webs could change how cascading effects of predators manifest within marine communities.
Increases in subsistence farming due to land reform have negligible impact on bird communities in Zimbabwe
Authors: Pringle Stephen , Chiweshe Ngoni , Dallimer Martin
Published: February 2022

Habitat alterations resulting from land‐use change are major drivers of global biodiversity losses. In Africa, these threats are especially severe. For instance, demand to convert land into agricultural uses is leading to increasing areas of drylands in southern and central Africa being transformed for agriculture. In Zimbabwe, a land reform programme provided an opportunity to study the biodiversity response to abrupt habitat modification in part of a 91,000 ha dryland area of semi‐natural savannah used since 1930 for low‐level cattle ranching. Small‐scale subsistence farms were created during 2001–2002 in 65,000 ha of this area, with ranching continuing in the remaining unchanged area. We measured the compositions of bird communities in farmed and ranched land over 8 years, commencing one decade after subsistence farms were established. Over the study period, repeated counts were made along the same 45 transects to assess species' population changes that may have resulted from trait‐filtering responses to habitat disturbance. In 2012, avian species' richness was substantially higher (+8.8%) in the farmland bird community than in the unmodified ranched area. Temporal trends over the study period showed increased species' richness in the ranched area (+12.3%) and farmland (+6.8%). There were increased abundances in birds of most sizes, and in all feeding guilds. New species did not add new functional traits, and no species with distinctive traits were lost in either area. As a result, species' diversity reduced, and functional redundancy increased by 6.8% in ranched land. By 2020, two decades after part of the ranched savannah was converted into farmland, the compositions of the two bird communities had both changed and became more similar. The broadly benign impact on birds of land conversion into subsistence farms is attributed to the relatively low level of agricultural activity in the farmland and the large regional pool of nonspecialist bird species.
Conductive‐noise suppression control improved by synchronous compensation for switching
Authors: Hanioka Shota , Iezawa Masahiro , Ogasawara Satoshi , Takemoto Masatsugu , Orikawa Koji , Ohara Shunsuke
Published: February 2022

In noise suppression control that switches between two inverters with opposite phases, the synchronization accuracy of switching limits the noise reduction and bandwidth. To improve the noise suppression control, this paper proposes a control method that detects the rise and fall of the inverter output voltage and compensates for the synchronization error between two inverters. The effectiveness of the proposed method was verified by applying it to the double‐three‐phase motor drive system; the synchronization error was reduced to 10 ns.
Efficient and simple simulation method for matching stress‐permeability test results
Authors: Zhang Tong , Zhang Cun , Song Ziyu
Published: February 2022

In the process of pressure‐relief mining in high gas coal seams and hydraulic fracturing of deep coalbed methane, a large number of irregular fractures are generated inside the coal, which becomes the main path for gas migration. The stress sensitivity of fractures directly affects the gas migration characteristics in the coal. For better matching stress‐permeability test results, a fluid–solid coupling simulation method with the joint stiffness changing method (JSCM), which accommodates fracture (or joint) stiffness through the stress acting on the fracture, is proposed. The stress sensitivity of permeability under different stress states was matched in a simulation and compared with a laboratory experiment. This method has the following advantages compared with the traditional joint stiffness fixing method (JSFM). (1) The JSCM does not need to set the residual joint aperture, which can match a wider range of stresses, so there is no upper limit in principle. (2) The JSCM can match the laboratory test results better than the JSFM. A parameter‐determining method for the JSCM is given for the flow test results. Based on the JSCM, the flow in an irregular fracture under different confining and axial stresses was determined. The results show that the occurrence of segmental fractures with different dip angles in persistent fractures determines the stress sensitivity of the fracture flow. With the increase in axial stress, the fracture aperture of the horizontal section is reduced, causing the decrease in horizontal section seepage capacity. It determines the whole flow of the persistent fracture. While with the increase in confining stress, the fracture aperture of vertical section is greatly reduced and causing flow rate of the whole fracture reducing greatly.
Between a rock and a hard place: The consequences of complex headquarters configurations for subsidiary R&D activities
Authors: Gillmore Edward , Andersson Ulf , Dellestrand Henrik
Published: February 2022

Research summary

Challenges related to the complexity of overlapping multiple partner headquarters configurations, the resulting power and political tensions between headquarters, and the consequent effects of multiple interventions in subsidiary value‐creating activities remain an understudied phenomenon. We present a rich case study of how complex overlapping headquarters configurations develop. Then, we present the processes underlying power and political tensions that lead to parenting disadvantages between partner headquarters. We find that multiple and simultaneous headquarters interventions place the subsidiary between a rock and a hard place, as it becomes subject to conflicting headquarters voices. We contribute to the literature on parenting in multinational enterprises through an increased understanding of overlapping headquarters configurations and the power and political tensions between headquarters configurations that stimulate interventions in subsidiary R&D mandates.

Managerial summary

Multinational enterprises are exposed to a plethora of complex challenges. To meet these challenges, the organizational structure often becomes complex. We focus on the causes and consequences of complex headquarters structures, that is, operating with multiple partner headquarters, within multinational enterprises in relation to the allocation and reallocation of subsidiary R&D mandates. We observe that headquarters interventions are driven by expectations and assigned roles to manage the multinational enterprise. Being aware of what partner headquarters are doing, that is, possessing system knowledge, can prevent redundant involvement by and competition between headquarters. Our findings indicate that if headquarters' knowledge of the system is low, this may cause the emergence of conflicting headquarters voices and considerable frustration among subsidiary managers.
FGF4 protects the liver from nonalcoholic fatty liver disease by activating the AMP‐activated protein kinase–Caspase 6 signal axis
Authors: Song Lintao , Wang Luyao , Hou Yushu , Zhou Jie , Chen Chuchu , Ye Xianxi , Dong Wenliya , Gao Huan , Liu Yi , Qiao Guanting , Pan Tongtong , Chen Qiong , Cao Yu , Hu Fengjiao , Rao Zhiheng , Chen Yajing , Han Yu , Zheng Minghua , Luo Yongde , Li Xiaokun , Chen Yongping , Huang Zhifeng
Published: February 2022

Background and Aims

NAFLD represents an increasing health problem in association with obesity and diabetes with no effective pharmacotherapies. Growing evidence suggests that several FGFs play important roles in diverse aspects of liver pathophysiology. Here, we report a previously unappreciated role of FGF4 in the liver.

Approach and Results

Expression of hepatic FGF4 is inversely associated with NAFLD pathological grades in both human patients and mouse models. Loss of hepatic Fgf4 aggravates hepatic steatosis and liver damage resulted from an obesogenic high‐fat diet. By contrast, pharmacological administration of recombinant FGF4 mitigates hepatic steatosis, inflammation, liver damage, and fibrogenic markers in mouse livers induced to develop NAFLD and NASH under dietary challenges. Such beneficial effects of FGF4 are mediated predominantly by activating hepatic FGF receptor (FGFR) 4, which activates a downstream Ca2+–Ca2+/calmodulin‐dependent protein kinase kinase beta–dependent AMP‐activated protein kinase (AMPK)‐Caspase 6 signal axis, leading to enhanced fatty acid oxidation, reduced hepatocellular apoptosis, and mitigation of liver damage.

Conclusions

Our study identifies FGF4 as a stress‐responsive regulator of liver pathophysiology that acts through an FGFR4‐AMPK‐Caspase 6 signal pathway, shedding light on strategies for treating NAFLD and associated liver pathologies.
Mechanisms and molecules: What are the treatment targets for primary biliary cholangitis?
Authors: Mayo Marlyn J.
Published: February 2022

Treatment of primary biliary cholangitis (PBC) with ursodeoxycholic acid (UDCA) is not always sufficient to prevent progression to hepatic decompensation and/or need for liver transplant. Adjuvant therapy with obeticholic acid may provide additional biochemical improvements in some patients, but it is not well‐tolerated by patients with significant itch or advanced cirrhosis. Thus, new and creative approaches to treating patients with PBC are important to identify. This review discusses major potential therapeutic targets in PBC and provides examples of some specific agents currently in development for the treatment of PBC. Targets are broadly classified into those which strive to modify bile, inflammation, cell survival, or fibrosis. In bile, shrinking the size of the bile acid pool or modifying the quality of the bile by making it more hydrophilic or enriched in phosphatidylcholine may ameliorate cholestatic injury. Biliary epithelial cell survival may be extended by fortifying the bicarbonate umbrella or improving cell membrane integrity. Autoimmunity and cholangitis have the potential to be improved via regulation of the immune system. Targeting cytokines, immune checkpoints, and anti‐mitochondrial antibodies are examples of a more focused immunosuppression approach. Stem cell therapy and lymphocyte trafficking inhibition are more novel methods of broad immune regulation. Anti‐fibrotic therapies are also potentially useful for preventing progression of PBC. The nuclear hormone receptors, farnesoid X receptor (FXR) and peroxisome proliferator–activated receptor (PPAR) regulate many of these pathways: cholestasis, inflammation, and fibrosis, which is why they are being enthusiastically pursued as potential therapeutic targets in PBC.
Revealing subsurface processes in the Uhlířská catchment through combined modelling of unsaturated and saturated flow
Authors: Vitvar Tomáš , Jankovec Jakub , Šanda Martin
Published: February 2022

A novel transferable modelling approach was applied to reveal subsurface flow processes and thus complement, verify, and enhance the conceptual knowledge of the small (1.78 km2) mountainous experimental catchment Uhlířská in the northern part of the Czech Republic. We used the S1D model to simulate flow and tracer movement in the vadose zone. MODFLOW‐2000, MODPATH and MT3DS models were used to determine residence time and flow trajectories in the saturated zone. The isotopic tracers 3H and 3H/3He were used to calibrate the groundwater model in the deeper aquifer layers. The modelling approach was established to enhance our understanding and quantification of interactions between the hillslope (82% of the area) and wetland (18% of the area), as well as the aquifer beneath the catchment. Numerical methods corroborated the estimated groundwater residence times and provided a catchment water balance in support of process knowledge. The combined modelling yielded the following water balance for the period 1961–2014: 1220 mm annual precipitation amount, 456 mm of percolation through the soil matrix domain on hillslopes, 534 mm of water through the hillslope preferential domain, and 22 mm of water through the matrix of the riparian wetland. This partitioning resulted in an area‐weighted average annual groundwater recharge of 430 mm. The water residence time on the hillslopes did not exceed 1 year, and was about 10 years for the saturated zone, with 20% of water older than 100 years in the deepest part of the aquifer. The conceptual knowledge of subsurface hydrological processes combined with numerical modelling, computation of water balance and isotope‐supported calibration is considered innovative, particularly the 3H/3He method to determine water residence times of young groundwater in the saturated zone. Lessons learned and recommendations are presented to apply the knowledge from the Uhlířská in the broad context of small research catchments.
Carbon concentrations in natural and restoration pools in blanket peatlands
Authors: Chapman Pippa J. , Moody Catherine S. , Turner T. Edward , McKenzie Rebecca , Dinsmore Kerry J. , Baird Andy J. , Billett Mike F. , Andersen Roxane , Leith Fraser , Holden Joseph
Published: February 2022

Open‐water perennial pools are common natural features of peatlands globally, and peatland restoration often results in new pool creation, yet the concentrations of different forms of aquatic carbon (C) in natural and artificial restoration pools are not well studied. We compared carbon concentrations in both natural pools and restoration pools (4–15 years old) on three blanket peatlands in northern Scotland. At all sites, restoration pools were more acidic and had mean dissolved organic carbon (DOC) concentrations in restoration pools of 23, 22, and 31 mg L−1 compared with natural pool means of 11, 11 and 15 mg L−1 respectively across the three sites. Restoration pools had a greater fulvic acid prevalence than the natural pools and their DOC was more aromatic. Restoration pools were supersaturated with dissolved CO2 at around 10 times atmospheric levels, whereas for natural pools, CO2 concentrations were just above atmospheric levels. Dissolved CH4 concentrations were not different between pool types, but were ~200 times higher than atmospheric levels. Regular sampling at one of the peatland sites over 2.5 years showed that particulate organic carbon (POC) concentrations were generally below 7 mg L−1 except during the warm, dry summer of 2013. At this regularly‐sampled site, natural pools were found to process DOC so that mean pool outflow concentrations in overland flow were significantly lower than mean inflow DOC concentrations. Such an effect was not found for the restoration pools. Soil solution and pool water chemistry, and relationships between DOC and CO2 concentrations suggest that different processes are controlling the transformation of C, and therefore the form and amount of C, in natural pools compared to restoration pools.
Reduced fetal urine production rate—An early marker of fetal inflammatory response syndrome in preterm premature rupture of membranes: Prospective cohort study
Authors: Jain Ankita , Aggarwal Richa , Gupta Natasha , Mehndiratta Mohit , Gogoi Priyanka , Batra Prerna , Agarwal Rachna
Published: February 2022

Objective

To find association between fetal urine production rate (FUPR) and fetal inflammatory response syndrome (FIRS) in preterm premature rupture of membranes (PPROM).

Methods

A prospective cohort study of 70 pregnant women with PPROM at 28–34 weeks of pregnancy was conducted. FUPR was calculated by performing serial fetal bladder volume measurements ultrasonographically and was repeated weekly until delivery. After delivery, cord blood interleukin‐6 (IL‐6) levels were measured. Placental tissue histopathology was performed and neonatal outcomes were noted.

Results

Out of 70 recruited patients with PPROM, 44 had evidence of FIRS (62.86%). Mean FUPR at the time of delivery was significantly reduced in neonates with evidence of FIRS compared with the Non‐FIRS group (13.89 ± 8.06 ml/h vs. 25.89 ± 4.94 ml/h). Out of 41 patients with reduced FUPR, 39 neonates had FIRS whereas only five out of 29 neonates with normal FUPR had FIRS (P < 0.001). Severe neonatal morbidity was found in 24 out of 41 (58.54%) neonates with reduced FUPR prenatally. The occurrence of respiratory distress syndrome, necrotizing enterocolitis, and sepsis was significantly high in neonates with reduced FUPR.

Conclusion

Reduced FUPR is strongly associated with FIRS in cases of PPROM and hence can be used as an early predictor of adverse neonatal outcomes.
Preoperative detection of occult endometrial malignancies in endometrial hyperplasia to improve primary surgical therapy: A scoping review of the literature
Authors: Laban Mohamed , El‐Swaify Seif Tarek , Ali Sara H. , Refaat Mazen A. , Sabbour Mohamed , Farrag Nourhan
Published: February 2022

The risk of undertreating occult endometrial cancer is a problem faced by gynecologists when treating endometrial hyperplasia. The objective of this study is to highlight diagnostic adjuncts to endometrial sampling techniques to improve preoperative detection of co‐existing cancer. A systematic search of databases till July 2021: PubMed, ISI‐Clarivate Web of Science, Scopus, and CENTRAL. A search of the related literature was also carried out. Two authors screened potential studies. Studies were included if they examined the diagnostic performance of any predictors of concurrent cancer in patients diagnosed with endometrial hyperplasia. Authors charted variables related to literature characteristics (e.g., authors, year of publication), population characteristics (e.g., preoperative diagnoses), and variables related to our research questions (e.g., postoperative diagnoses, risk predictors). After screening 591 potential studies, 28 studies were included. Studies included the data of 7409 endometrial hyperplasia patients with 2377 concurrent endometrial cancer cases (32.1%). Forty potential predictors of concurrent cancer were investigated. We examined three categories of potential predictors: clinical (22 studies), histopathologic/imaging (16 studies), and molecular (six studies) predictors. The proposed predictors, age, menopausal status, diabetes, WHO and endometrial intraepithelial neoplasia histopathologic criteria, pelvic magnetic resonance imaging, and molecular profiling are promising diagnostic adjuncts.
Effectiveness of ultrasound algorithm in prenatal diagnosis of hemoglobin Bart’s disease among pregnancies at risk
Authors: Harn‐a‐morn Panwad , Wanapirak Chanane , Sirichotiyakul Supatra , Srisupundit Kasemsri , Tongprasert Fuanglada , Luewan Suchaya , Tongsong Theera
Published: February 2022

Objective

To evaluate the effectiveness of ultrasound algorithm in diagnosis of fetal Hb Bart’s disease among pregnancies at risk.

Methods

Pregnancies at risk underwent ultrasound for the first time at 12–14 weeks of gestation and serial ultrasound every 2–4 weeks until 24 weeks to identify pre‐hydropic signs. The invasive procedure was omitted in case of no pre‐hydropic signs.

Results

A total of 237 fetuses were recruited, including 53 affected and 184 unaffected fetuses. The algorithm has a sensitivity of 100% in the detection of fetal Hb Bart’s disease with a false positive rate of 10.9%. Of the affected group, the mean gestational age at the time of diagnosis was 15.5 ± 2.6 week. 30.8% of all pregnancies at risk underwent invasive procedures. The algorithm had a 70% reduction in the rate of invasive procedures among pregnancies at risk without missing the affected cases.

Conclusions

The algorithm is highly effective in the early detection of fetal Hb Bart’s disease with a detection rate of 100%, and invasive diagnosis can be avoided in about 70% of cases. Thus, this algorithm should be used as a guideline for prenatal diagnosis of fetal Hb Bart’s disease, especially in geographical areas of high prevalence.
Predictors of prior unsuccessful pharmacy abortion attempts among women presenting for abortion in government certified clinics in Nepal
Authors: Ahlbach Chris , Puri Mahesh C. , Daniel Sara , Rocca Corinne H. , Karki Sunita , Foster Diana Greene
Published: February 2022

Objective

Although abortion in Nepal is broadly legal and free of charge, many women seek abortion care outside the legal system, including from pharmacies. We evaluated the prevalence of, and factors associated with, prior unsuccessful abortion attempts among women presenting to 14 randomly‐selected government approved abortion health facilities across Nepal.

Methods

Eligible participants were recruited in 2019 by trained research staff from certified abortion facilities. Participants (n = 1160) completed research staff‐administered baseline surveys. We used multivariable mixed‐effects logistic regression models to evaluate factors associated with having attempted pharmacy abortion prior to coming to the health facility.

Results

Almost one in seven (14%) women had tried to end their pregnancy before presenting to a participating clinic, often (9%) using medication obtained from a pharmacy. Women who lived farther from the clinic (aOR 1.28 per log hours travel time, 95% CI 1.10–1.49) and who reported financial difficulty in accessing the clinic (19% vs. 10%, aOR 2.10, 95% CI 1.20–3.70) had increased odds of having tried to access abortion through a pharmacy.

Conclusion

Integrating pharmacies into the legal network of abortion providers may improve access to safe care, particularly for rural women with financial and practical travel limitations.
The economic toll of COVID‐19: A cohort study of prevalence and economic factors associated with postpartum depression in Kenya
Authors: Sudhinaraset May , Landrian Amanda , Mboya John , Golub Ginger
Published: February 2022

Objective

The aim of the study is to examine the risk of postpartum depression (PPD) among women who delivered during the COVID‐19 pandemic compared to women who delivered before the COVID‐19 pandemic and how economic challenges are associated with PPD.

Methods

Data were collected from 2332 women. This includes 1197 women from healthcare facilities in 2019 who were followed up at 2–4 and 10 weeks postpartum. Additionally, we recruited 1135 women who delivered from March 16, 2020 onward when COVID‐19 restrictions were mandated in Kenya in the same catchment areas as the original sample to compare PPD rates.

Results

Adjusting for covariates, women who delivered during COVID‐19 had 2.5 times higher odds of screening positive for PPD than women who delivered before COVID‐19 (95% confidence interval [CI] 1.92–3.15). Women who reported household food insecurity, required to pay a fee to cover the cost of PPE during labor and delivery and/or postnatal visit(s), and those who reported COVID‐19 employment‐related impacts had a higher likelihood of screening for PPD compared to those who did not report these experiences.

Conclusion

The COVID‐19 pandemic has greatly increased the economic vulnerability of women, resulting in increases in PPD.
Satellite network‐oriented visualization analysis of 3D geographic information
Authors: Li Xiuxia
Published: February 2022

The development of computer technology and network technology makes network‐oriented three‐dimensional (3D) visualization an important development direction in the computer field. And the arrival of the era of big data makes it irreplaceable in dynamic simulation, disaster simulation, and supporting decision‐making of geographic information systems (GIS). However, the composition in GIS is not static, but dynamically changing, even moving at high speed, such as various transportation vehicles, which brings great challenges to real‐time and accurate visualization. How to realize real‐time visualization of dynamically changing GIS is of urgent significance. In this paper, the characteristics of real‐time positioning of satellite network are considered to design a visualization and analysis method based on satellite network for 3D geographic information (SN‐3DGVA). It can sense the change of objects and locate the corresponding change tracks and position, so as to perform 3D geographic visualization analysis.
Direct C‐2 arylation of quinoxaline with arylhydrazine salts as arylation reagents
Authors: Wang Xing , Wang Bing , Miao Jing , Chen Yi , Zhu Gaofeng , Zhang Jiquan , Wang Jianta , Wang Haibo , Tang Lei , Wang Cong
Published: February 2022

A transition metal‐free synthesis of 2‐arylquinoxaline is achieved by using arylhydrazine salt as an aryl radical arylation reagent and air as an oxidant in the presence of K2CO3. This protocol features metal‐free, no additives, mild reaction conditions, environment friendly, and can be used to construct biologically active molecules containing 2‐phenylquinoxaline structure.