bluuebunny/crossref_metadata_2025 huggingface dataset:
Geomorphic diversity of the Indian sub‐continent: Progress and updates
Authors: Sinha Rajiv
Published: April 2021

This commentary is designed to highlight the recent contributions on Indian geomorphology that have been published in Earth Surface Processes and Landforms (ESPL). A large number of papers included in this commentary have been published as part of the special issue on Indian geomorphology. However, I have taken the liberty of including a few others that appeared in ESPL in the last couple of years. These papers have covered a variety of topics ranging from erosion rates in Himalayan basins, miliolites in peninsular India, flood risk, connectivity concept, socio‐hydrology, and paleoclimatic reconstruction from lake sediments. They have also utilized a wide range of methodologies and tools including fractals, remote sensing, cosmogenic nuclides, and modelling. It is hoped that this commentary will put the diversity of Indian geomorphology in the correct perspective and will encourage geomorphologists across the world to continue their excellent research.
An island arc origin of Jurassic plagiogranite in the Shiquanhe ophiolite, western Bangong Suture, Tibet: Zircon U–Pb chronology, geochemistry, and tectonic implications of Bangong Meso‐Tethys
Authors: Li Wei , Liu Nina , Nayak Ranjit , Ma Yaoliang , Wang Jinjun , Hu Xichong , Pang Jiehui , Huang Weile , Zhong Yun , Liu Weiliang
Published: April 2021

The plagiogranites in ophiolites are minor in volume but can provide crucial information for the origin and tectonic evolution of ancient oceanic lithosphere. This paper presents the geochronology and geochemistry of a newly discovered plagiogranite in the Shiquanhe ophiolite, from the west end of the Shiquanhe‐Jiali ophiolite sub‐belt, Bangong Suture, central Tibet. Zircon U–Pb dating of two samples yields Middle Jurassic ages (167.4 ± 1.2 Ma and 167.5 ± 1.5 Ma). The plagiogranite has positive whole‐rock εNd(t) (4.2–4.9) and zircon εHf(t) (9.6–14.3) values, high Th/Nb ratios (0.6–2.8) but relatively low La/Nb ratios (0.9–9.9), indicating that it was possibly derived from a depleted mantle with the contribution of minor subducted sediments. The LREE‐enrichment but HREE‐flat patterns with negative Eu anomalies and negative Nb‐Ti anomalies resemble those of shear‐type plagiogranites, which mean that this rock was likely formed by partial melting of metabasite. Combined with the plagiogranite which does not exhibit chilled contacts against the Shiquanhe ophiolitic metabasite, suggests that the plagiogranite may have been derived from the associated ophiolitic metabasite. Geochemical calculating and modelling indicate that the plagiogranite was possibly produced by a low degree (<10%) partial melting of metabasite and replenished by minor sediments melts at low temperature (<800 °C) and low pressure (<0.1 GPa) conditions. The Shiquanhe plagiogranite, together with the contemporaneous Lagkorco plagiogranite in the same ophiolite sub‐belt, indicates that an intra‐oceanic island arc system was developed in the Bangong Meso‐Tethys during the Middle Jurassic.
Red meat consumption, cooking mutagens, NAT1/2 genotypes and pancreatic cancer risk in two ethnically diverse prospective cohorts
Authors: Huang Brian Z. , Wang Songren , Bogumil David , Wilkens Lynne R. , Wu Lang , Blot William J. , Zheng Wei , Shu Xiao‐Ou , Pandol Stephen J. , Le Marchand Loïc , Setiawan Veronica Wendy
Published: April 2021

There is limited evidence on the association between red meat consumption and pancreatic cancer among ethnic minorities. We assessed this relationship in two large prospective cohorts: the Multiethnic Cohort Study (MEC) and the Southern Community Cohort Study (SCCS). Demographic, dietary and other risk factor data were collected at cohort entry. Red meat intake was assessed using cohort‐specific validated food frequency questionnaires. Incident pancreatic cancer cases were identified via linkages to state cancer registries. Cox regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association of red meat intake with pancreatic cancer risk in each cohort. We performed additional analyses to evaluate cooking methods, mutagens and effect modification by NAT1/2 genotypes. From a total of 184 542 (MEC) and 66 793 (SCCS) at‐risk participants, we identified 1618 (MEC) and 266 (SCCS) incident pancreatic cancer cases. Red meat consumption was associated with pancreatic cancer risk in the MEC (RRQ4vsQ1 1.18, 95% CI 1.02‐1.37) and with borderline statistical significance in the SCCS (RRQ4vsQ1 1.31, 95% CI 0.93‐1.86). This association was significant in African Americans (RRQ4vsQ1 1.49, 95% CI 1.06‐2.11) and Latinos (RRQ4vsQ1 1.44, 95% CI 1.02‐2.04) in the MEC, and among African Americans (RRQ4vsQ1 1.55, 95% CI 1.03‐2.33) in the SCCS. NAT2 genotypes appeared to modify the relationship between red meat and pancreatic cancer in the MEC (pinteraction = 0.03). Our findings suggest that the associations for red meat may be strongest in African Americans and Latinos. The mechanisms underlying the increased risk for these populations should be further investigated.
The impact of a mother–infant intervention on parenting and infant response to challenge: A pilot randomized controlled trial with adolescent mothers in El Salvador
Authors: Valades Jimena , Murray Lynne , Bozicevic Laura , De Pascalis Leonardo , Barindelli Florencia , Meglioli Alejandra , Cooper Peter
Published: April 2021

A pilot randomized controlled trial (RCT) was conducted in El Salvador of an intervention (‘Thula Sana’) previously shown to enhance maternal sensitivity and infant security of attachment in a South African sample. In El Salvador, trained community workers delivered the intervention from late pregnancy to 6 months postpartum as part of a home‐visiting programme. The sample comprised 64 pregnant adolescent women, aged 14–19 years, living in predominantly rural settings. They were randomised to receive either the intervention or normal care. Demographic information was collected at baseline and, immediately post‐intervention, blind assessments were made of parental sensitivity and infant emotion regulation. The intervention was found to have a substantial positive impact on maternal sensitivity. Further, compared to control group, infants in the intervention group showed more regulated behaviour: in a social challenge task they showed more attempts to restore communication, and in a non‐social challenge task they showed more social and goal‐directed behaviour. This replication and extension of the South African findings in a small El Salvador sample shows promise and justifies the conduct of a large‐scale RCT in a Central or South American context.
Is a 20 gauge fenestrated intravenous catheter non‐inferior to a 18 gauge standard catheter for apheresis procedures? A pilot study
Authors: Armendariz Tomas , West James , Olson DaiWai M. , Stutzman Sonja E. , De Simone Nicole
Published: April 2021

Background

Peripheral venous access has been promoted as the safest, quickest, and most easily achievable route for performing apheresis procedures by the American Society for Apheresis' Choosing Wisely campaign. The current literature regarding catheter size and selection for both draw and return access is limited. Furthermore, the Infusion Nurses Society recommends using the smallest gauge catheter possible for the prescribed therapy in order to limit vein trauma and phlebitis. Since there is a lack of evidence to guide selection of catheter size for return access during therapeutic apheresis procedures (TAPs) for patients with chronic conditions, this pilot study seeks to compare the performance of a 20‐gauge fenestrated (20G) catheter to a standard 18‐gauge (18G) intravenous catheter.

Methods

This non‐inferiority pilot study randomized 26 subjects during 74 TAPs to either 20G fenestrated catheter or 18G standard catheter.

Results

There were no statistically significant differences for variables associated with the efficiency of the TAPs comparing 20G to 18G catheter for inlet rate (P = .8666), return pressure (P = .9427), blood processed (P = .4318), or total procedure time (P = .3184).

Conclusion

The results from this pilot study suggest that 20G fenestrated catheter is non‐inferior to 18G standard catheters. Additional studies with increased power are warranted to confirm these findings.
[10]annulene: Electrocyclization mechanisms
Authors: Palmeiro Raúl , Castaño Obis
Published: April 2021

The mechanism of 6‐π electrocyclization of all‐cis, mono‐trans, and double‐trans [10]annulene to yield 4a,8a‐dihydronaphthalene has been explored at various quantum‐chemical methods. The mono‐trans configuration cyclizes preferentially to trans‐4a,8a‐dihydronaphthalene, in agreement with the experimental results. The cyclization of the all‐cis configuration requires firstly a bond‐shifting to the naphthalene‐like conformation of double‐trans [10]annulene, which is the rate‐limiting step, and finally its azulene‐like conformation electrocyclizes quickly to cis‐4a,8a‐dihydronaphthalene. Its experimental rate coefficient is consistent with the computed one for the cyclization of the all‐cis configuration, unlike the calculated one for the double‐trans configuration. These results confirm the configurations assigned by Masamune et al. to the two isomers which they isolated.
Fast non‐iterative calculation of solvation energies for water and non‐aqueous solvents
Authors: Vyboishchikov Sergei F. , Voityuk Alexander A.
Published: April 2021

We propose an efficient and accurate non‐iterative method, dubbed uESE, for calculating solvation free energies. Apart from a COSMO‐like electrostatic term, the model takes into account non‐electrostatic contributions, which depend on atomic surfaces, induced surface charge densities, and the molecular volume. uESE is tested on 35 polar and 57 non‐polar solvents. The calculated and experimental solvation free energies are compared for 2892 systems. The method exhibits an excellent performance, which is superior to major solvation methods. The mean absolute error of predicted solvation energies is found below 1 kcal/mol for neutral solutes and below 3 kcal/mol for ions. The calculated data are almost independent of the quantum‐chemical method or/and basis sets employed.
Roles of FAM134B in diseases from the perspectives of organelle membrane morphogenesis and cellular homeostasis
Authors: Zhu Luoyi , Wang Xinxia , Wang Yizhen
Published: April 2021

Family with sequence similarity 134 member B (FAM134B)/RETREG1/JK1 is a novel gene with recently reported roles in various diseases. Understanding the function and mechanism of action of FAM134B is necessary to develop disease therapies. Notably, emerging data are clarifying the molecular mechanisms of FAM134B function in organelle membrane morphogenesis and the regulation of signaling pathways, such as the Wnt and AKT signaling pathways. In addition, transcription factors, RNA N6‐methyladenosine‐mediated epigenetic regulation, microRNA, and small molecules are involved in the regulation of FAM134B expression. This review comprehensively considers recent studies on the role of FAM134B and its potential mechanisms in neurodegenerative diseases, obesity, viral diseases, cancer, and other diseases. The functions of FAM134B in maintaining cell homeostasis by regulating Golgi morphology, endoplasmic reticulum autophagy, and mitophagy are also highlighted, which may be the underlying mechanism of FAM134B gene mutation‐induced diseases. Moreover, the molecular mechanisms of the FAM134B function during numerous biological processes are discussed. This review provides novel insights into the functions and mechanisms of FAM134B in various diseases, which will inform the development of effective drugs to treat diseases.
O‐GlcNAcylation promotes the migratory ability of hepatocellular carcinoma cells via regulating FOXA2 stability and transcriptional activity
Authors: Huang Huang , Wu Qiong , Guo Xinyi , Huang Tianmiao , Xie Xueqin , Wang Lingyan , Liu Yangzhi , Shi Lin , Li Wenli , Zhang Jianing , Liu Yubo
Published: April 2021

O‐GlcNAcylation is a posttranslational modification that regulates numerous nuclear and cytoplasmic proteins and is emerging as a key regulator of various biological processes, such as transcription, signal transduction, and cell motility. Although increasing evidence has shown that elevated levels of global O‐GlcNAcylation are linked to the metastasis in hepatocellular carcinoma (HCC) cells, the underlying mechanism is still ambiguous. In this study, we demonstrated that forkhead box protein A2 (FOXA2), an essential transcription factor for liver homeostasis and HCC developing, was O‐GlcNAcylated by O‐GlcNAc transferase (OGT) and regulates HCC cells migration and invasion. Opposite FOXA2 and OGT expression tendency were observed in HCC tissues, and lower FOXA2 levels predicted a poor prognosis in HCC patients. The reduction of FOXA2 in HCC cells was found to be inversely correlated with the cellular O‐GlcNAcylation and cell migratory ability. Notably, we found that FOXA2 was modified by O‐GlcNAcylation and that O‐GlcNAcylation activated the ubiquitination degradation of FOXA2 in highly metastatic HCC cells. Although this modification did not affect FOXA2 nuclear localization capability, O‐GlcNAcylation on FOXA2 was key for attenuating FOXA2‐mediated transcription. O‐GlcNAcylation decreased the transcription of FOXA2 downstream target gene E‐cadherin and it ultimately promoted O‐GlcNAcylation‐mediated HCC cell migration and invasion. The results provide insights into the role of O‐GlcNAcylation in regulating FOXA2 activity and suggest its important implications in HCC metastasis.
Roles and mechanisms of YAP/TAZ in orthodontic tooth movement
Authors: Deng Lanzhi , Chen Yilin , Guo Jiusi , Han Xianglong , Guo Yongwen
Published: April 2021

Yes‐associated protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ) are transcriptional coactivators encoded by paratactic homologous genes, shuttle‐crossing between cytoplasm and nucleus to regulate the gene expression and cell behavior and standing at the center place of the sophisticated regulatory networking of mechanotransduction. Orthodontic tooth movement (OTM) is a process in which extracellular mechanical stimuli are transformed into intracellular biochemical signals to regulate cellular responses and tissue remodeling. Literature studies have confirmed that YAP/TAZ plays an important role not only in embryonic development, homeostasis and tumorigenesis, but also in mechanical‐biochemical signal transduction of periodontal tissues under the mediation of various signal molecules in its upstream and downstream. Herein, we review the advances in the roles and mechanisms of YAP/TAZ in OTM to provide insights for better understanding and further study of the OTM and possible targeted clinical intervention in orthodontic treatment.
Transcriptional regulation of the basic helix‐loop‐helix factor AmeloD during tooth development
Authors: Al Thamin Shahad , Chiba Yuta , Yoshizaki Keigo , Tian Tian , Jia LingLing , Wang Xin , Saito Kan , Li Jiyao , Yamada Aya , Fukumoto Satoshi
Published: April 2021

The epithelial‐mesenchymal interactions are essential for the initiation and regulation of the development of teeth. Following the initiation of tooth development, numerous growth factors are secreted by the dental epithelium and mesenchyme that play critical roles in cellular differentiation. During tooth morphogenesis, the dental epithelial stem cells differentiate into several cell types, including inner enamel epithelial cells, which then differentiate into enamel matrix‐secreting ameloblasts. Recently, we reported that the novel basic‐helix‐loop‐helix transcription factor, AmeloD, is actively engaged in the development of teeth as a regulator of dental epithelial cell motility. However, the gene regulation mechanism of AmeloD is still unknown. In this study, we aimed to uncover the mechanisms regulating AmeloD expression during tooth development. By screening growth factors that are important in the early stages of tooth formation, we found that TGF‐β1 induced AmeloD expression and ameloblast differentiation in the dental epithelial cell line, SF2. TGF‐β1 phosphorylated ERK1/2 and Smad2/3 to induce AmeloD expression, whereas treatment with the MEK inhibitor, U0126, inhibited AmeloD induction. Promoter analysis of AmeloD revealed that the proximal promoter of AmeloD showed high activity in dental epithelial cell lines, which was enhanced following TGF‐β1 stimulation. These results suggested that TGF‐β1 activates AmeloD transcription via ERK1/2 phosphorylation. Our findings provide new insights into the mechanisms that govern tooth development.
Working Hard to Take the Easy Way Out: How the Need for Cognitive Closure Shapes Strategic Effort Investment to Ease Future Decision Making
Authors: Otto Ashley S. , Clarkson Joshua J. , Martin Nathanael S.
Published: April 2021

Consumers make countless decisions each day that force them to determine the amount of effort they are willing to invest into the decision process. Due to their desire for immediate resolution and propensity to seize upon available options, individuals high in the need for cognitive closure make decisions that are traditionally associated with reduced effort investment. Counter to this traditional perspective, this research demonstrates that those seeking closure strategically invest effort into the decision process, so long as the initial effort investment is expected to simplify similar decisions in the future. Three experiments demonstrate that those motivated by closure put forth greater effort when they expect to repeat the decision (Experiment 1) and in contexts where a justifiable choice option is not readily available (Experiment 2). Furthermore, this effort investment is shown to payoff in terms of streamlining subsequent decision making (Experiment 3). These findings detail the strategic use of effort by those seeking closure to ease future decision making and thus provide a conceptual framework for when and why those seeking closure allocate effort in decision making.
Ultrastructure of antennal sensilla of Copidosomopsis nacoleiae (Eady) (Hymenoptera: Chalcidoidea: Encyrtidae), a parasitoid of Diaphania angustalis (Snellen) (Lepidoptera: Crambidae)
Authors: Zhang Yu‐Jing , Chen Dong‐Yu , Chao Xue‐Ting , Dong Zi‐Shu , Huang Zong‐You , Zheng Xia‐Lin , Lu Wen
Published: April 2021

The antennal sensilla of Copidosomopsis nacoleiae (Eady) (Hymenoptera: Chalcidoidea: Encyrtidae) were observed under scanning and transmission electron microscopy in this study. The antennae of C. nacoleiae are geniculate, and the flagellum is composed of five subsegments in males and six in females. Six types of sensilla were observed, including sensilla trichodea, sensilla chaetica, sensilla basiconic capitate pegs, sensilla placodea, sensilla basiconica, and Böhm's bristles. Sensilla trichodea were evenly distributed throughout the antennae. Sensilla chaetica, sensilla basiconic capitate pegs and sensilla placodea were found on the flagellomeres. Sensilla basiconica were only found on the club, and Böhm's bristles were found on the radicle and the pedicel. Sensilla trichodea, sensilla placodea, sensilla chaetica, and sensilla basiconic capitate pegs were found to be the most common sensilla of the parasitoids in the superfamily Chalcidoidea. The external and internal characteristics, types, number, distribution, and dimensions of these sensilla are described, and their possible functions are discussed in accordance with host‐detection behavior. Future studies on the host location mechanisms of C. nacoleiae will be based upon these observations.
Examining sources and pathways of phosphorus transfer in a ditch‐drained field
Authors: Mosesso Lauren R. , Buda Anthony , Collick Amy , Kennedy Casey , Folmar Gordon , Shober Amy
Published: April 2021

Understanding the processes that mobilize and transport dissolved phosphorus (P) during storms is critical to managing P in flat landscapes with open ditch drainage and legacy soil P. In this study, we used routine baseflow monitoring and intensive storm sampling at a ditch‐drained site on Maryland's Lower Eastern Shore (July 2017–September 2018) to assess whether concentration–discharge (C‐Q) relationships and chemical and isotopic hydrograph separation could provide insight into the processes that mobilize and transport dissolved P in ditch drainage. Using a segmented regression model, we determined that long‐term C‐Q relationships for dissolved P differed above and below a discharge threshold of 6.4 L s–1. Intensive storm sampling revealed that small storms (n = 3) occurring at or below the discharge threshold generally exhibited complex hysteresis and dissolved P dilution patterns that were consistent with deeper (>122 cm) groundwater inputs with low dissolved P concentrations (0.04 mg L–1). In contrast, large storms occurring well above the discharge threshold (n = 4) induced rising water tables and preferential flow pathways that most likely tapped dissolved P–enriched shallow (<20 cm) soil waters (0.89 mg L–1), producing consistent clockwise hysteresis and dissolved P flushing patterns. Notably, chemical and isotope hydrograph separation during two of the largest storms revealed significant event water fractions (59–68%) that strongly suggested a role for the rapid delivery of dissolved P via preferential flow pathways. Findings highlight the need to mitigate vertical P stratification as a means for reducing dissolved P flushing from ditch‐drained landscapes with legacy P.
Permanent endoscopic gallbladder stenting versus removal of gallbladder drainage, long‐term outcomes after management of acute cholecystitis in high‐risk surgical patients for cholecystectomy: Multi‐center retrospective cohort study
Authors: Maruta Akinori , Iwashita Takuji , Iwata Keisuke , Yoshida Kensaku , Uemura Shinya , Mukai Tsuyoshi , Yasuda Ichiro , Shimizu Masahito
Published: April 2021

Background

Endoscopic transpapillary gallbladder drainage (EGBD) has been reported as an effective gallbladder drainage treatment option for acute cholecystitis in high‐risk surgical patients. However, the long‐term outcomes such as cholecystitis' recurrence rate after placement of EGB stenting (EGBS) have not been well studied yet.

Aims

The aim of the present study was to compare the long‐term outcome of EGBS and removal of gallbladder drainage after percutaneous transhepatic gallbladder drainage (PTGBD) or endoscopic nasogallbladder drainage (ENGBD) for acute cholecystitis in high‐risk surgical patients and clarify the usefulness of long‐term placement of EGBS.

Methods

We retrospectively studied 180 high‐risk surgical patients with acute cholecystitis between January 2010 and December 2018. The patients were divided into two groups: EGBS group (long‐term placement of EGBS) or Removal group (removal of drainage tube after PTGBD or ENGBD). Clinical outcomes, including long‐term results, were compared between the groups.

Results

The cumulative late adverse event (AE) rates were 5.0% and 22.1% in the EGBS and Removal group (P = .002), with a median follow‐up period of 375 and 307 days in the two groups, respectively. The cumulative cholecystitis recurrence rate was 5.0% (2/40) in the EGBS group and 16% (21/131) in the Removal group (P = .024), respectively. In the multivariate analysis for late AE, only EGBS was an independent risk factor with a decreasing value.

Conclusion

The permanent EGBS in high‐risk surgical patients with acute cholecystitis was considered effective in reducing the risk of late AE.
Targeted urine metabolomics with a graphical reporting tool for rapid diagnosis of inborn errors of metabolism
Authors: Steinbusch Laura K.M. , Wang Ping , Waterval Huub W.A.H. , Stassen Fons A.P.M. , Coene Karlien L.M. , Engelke Udo F.H. , Habets Daphna D.J. , Bierau Jörgen , Körver‐Keularts Irene M.L.W.
Published: April 2021

The current diagnostic work‐up of inborn errors of metabolism (IEM) is rapidly moving toward integrative analytical approaches. We aimed to develop an innovative, targeted urine metabolomics (TUM) screening procedure to accelerate the diagnosis of patients with IEM. Urinary samples, spiked with three stable isotope‐labeled internal standards, were analyzed for 258 diagnostic metabolites with an ultra‐high performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS) configuration run in positive and negative ESI modes. The software automatically annotated peaks, corrected for peak overloading, and reported peak quality and shifting. Robustness and reproducibility were satisfactory for most metabolites. Z‐scores were calculated against four age‐group‐matched control cohorts. Disease phenotypes were scored based on database metabolite matching. Graphical reports comprised a needle plot, annotating abnormal metabolites, and a heatmap showing the prioritized disease phenotypes. In the clinical validation, we analyzed samples of 289 patients covering 78 OMIM phenotypes from 12 of the 15 society for the study of inborn errors of metabolism (SSIEM) disease groups. The disease groups include disorders in the metabolism of amino acids, fatty acids, ketones, purines and pyrimidines, carbohydrates, porphyrias, neurotransmitters, vitamins, cofactors, and creatine. The reporting tool easily and correctly diagnosed most samples. Even subtle aberrant metabolite patterns as seen in mild multiple acyl‐CoA dehydrogenase deficiency (GAII) and maple syrup urine disease (MSUD) were correctly called without difficulty. Others, like creatine transporter deficiency, are illustrative of IEM that remain difficult to diagnose. We present TUM as a powerful diagnostic screening tool that merges most urinary diagnostic assays expediting the diagnostics for patients suspected of an IEM.
A generic emergency protocol for patients with inborn errors of metabolism causing fasting intolerance: A retrospective, single‐center study and the generation of www.emergencyprotocol.net
Authors: Rossi Alessandro , Hoogeveen Irene J. , Lubout Charlotte M. A. , de Boer Foekje , Fokkert‐Wilts Marieke J. , Rodenburg Iris L. , van Dam Esther , Grünert Sarah C. , Martinelli Diego , Scarpa Maurizio ,   CONNECT MetabERN Collaboration Group, Dekker Hanka , te Boekhorst Sebastiaan T. , van Spronsen Francjan J. , Derks Terry G. J.
Published: April 2021

Patients with inborn errors of metabolism causing fasting intolerance can experience acute metabolic decompensations. Long‐term data on outcomes using emergency letters are lacking. This is a retrospective, observational, single‐center study of the use of emergency letters based on a generic emergency protocol in patients with hepatic glycogen storage diseases (GSD) or fatty acid oxidation disorders (FAOD). Data on hospital admissions, initial laboratory results, and serious adverse events were collected. Subsequently, the website www.emergencyprotocol.net was generated in the context of the CONNECT MetabERN eHealth project following multiple meetings, protocol revisions, and translations. Representing 470 emergency protocol years, 127 hospital admissions were documented in 54/128 (42%) patients who made use of emergency letters generated based on the generic emergency protocol. Hypoglycemia (here defined as glucose concentration < 3.9 mmol/L) was reported in only 15% of hospital admissions and was uncommon in patients with ketotic GSD and patients with FAOD aged >5 years. Convulsions, coma, or death was not documented. By providing basic information, emergency letters for individual patients with hepatic GSD or the main FAOD can be generated at www.emergencyprotocol.net, in nine different languages. Generic emergency protocols are safe and easy for home management by the caregivers and the first hour in‐hospital management to prevent metabolic emergencies in patients with hepatic GSD and medium‐chain Acyl CoA dehydrogenase deficiency. The website www.emergencyprotocol.net is designed to support families and healthcare providers to generate personalized emergency letters for patients with hepatic GSD and the main FAOD.
Chemogenetic manipulation of astrocytic signaling in the basolateral amygdala reduces binge‐like alcohol consumption in male mice
Authors: Nwachukwu Kala N. , Evans William A. , Sides Tori R. , Trevisani Christopher P. , Davis Ambryia , Marshall S. Alex
Published: April 2021

Binge drinking is a common occurrence in the United States, but a high concentration of alcohol in the blood has been shown to have reinforcing and reciprocal effects on the neuroimmune system in both dependent and non‐dependent scenarios. The first part of this study examined alcohol's effects on the astrocytic response in the central amygdala and basolateral amygdala (BLA) in a non‐dependent model. C57BL/6J mice were given access to either ethanol, water, or sucrose during a “drinking in the dark” paradigm, and astrocyte number and astrogliosis were measured using immunohistochemistry. Results indicate that non‐dependent consumption increased glial fibrillary acidic protein (GFAP) density but not the number of GFAP+ cells, suggesting that non‐dependent ethanol is sufficient to elicit astrocyte activation. The second part of this study examined how astrocytes impacted behaviors and the neurochemistry related to alcohol using the chemogenetic tool, DREADDs (designer receptors exclusively activated by designer drugs). Transgenic GFAP‐hM3Dq mice were administered clozapine N‐oxide both peripherally, affecting the entire central nervous system (CNS), or directly into the BLA. In both instances, GFAP‐Gq‐signaling activation significantly reduced ethanol consumption and correlating blood ethanol concentrations. However, GFAP‐Gq‐DREADD activation throughout the CNS had more broad effects resulting in decreased locomotor activity and sucrose consumption. More targeted GFAP‐Gq‐signaling activation in the BLA only impacted ethanol consumption. Finally, a glutamate assay revealed that after GFAP‐Gq‐signaling activation glutamate concentrations in the amygdala were partially normalized to control levels. Altogether, these studies support the theory that astrocytes represent a viable target for alcohol use disorder therapies.
Work and suicide: An interdisciplinary systematic literature review
Authors: Howard Matt C. , Follmer Kayla B. , Smith Mickey B. , Tucker Raymond P. , Van Zandt Elise C.
Published: April 2021

Although organizational scholars have long been interested in employees' well‐being and occupational health, less work has focused specifically on suicide behaviors among employees. This dearth of research is concerning given that individuals spend a significant portion of their waking hours at work, and suicide deaths among American workers are on the rise. To encourage the study of work and suicide with the intent of ultimately reducing mortality, we first provide a theoretical framework that incorporates two eminent theories of suicide: interpersonal‐psychological theory of suicide and psychache theory of suicide. We then report the findings of an interdisciplinary systematic literature review that offers an overview of current research related to work and suicide, including antecedent, mediating, and moderating effects. The results of our systematic literature review are presented via the lens of our theoretical framework, supporting that it is an appropriate perspective to understand the relation of work and suicide. Finally, we conclude by identifying avenues for continued research on the interplay between work and suicide, again incorporating these research directions into our theoretical framework. Together, our manuscript integrates multiple domains of research, while addressing a timely and critical public health crisis that stems, in part, from employees' workplace experiences.
Outcomes of adverse drug events reported with potentially inappropriate medications in older adults, 2004–2017
Authors: Park Sharon K. , Luu Bao Tran
Published: April 2021

Background

Prescribing of potentially inappropriate medications (PIMs) in adults who are ≥65 years old have been associated with adverse drug events (ADEs).

Aim

To describe ADEs with PIMs in the older adults based on demographics, ADE severity level, and medication class.

Method

All ADEs reported to the U.S. Food and Drug Administration Adverse Event Reporting System between 1 January 2004 and 31 December 2017 were reviewed. Data were collected for any ADEs associated with PIMs in adults with ages ≥65 years per the Beers Criteria, including demographics, ADE severity, and ADE date. ADEs were further analysed for any death, hospitalisation, disability, and other serious outcomes associated with PIMs. Data were analysed descriptively.

Results

The number of reported ADEs increased steadily over the 13‐year period. Of the total 68 762 ADEs reported, 80.4% were serious ADEs and more women experienced ADEs (52.0%) than men (46.4%). Age group between 65–74 had a higher number of ADE reports than other groups. Of the 55 302 serious ADEs, 2723 were deaths. The anticoagulants class had the highest percentage of ADEs with death outcomes (57.3%), followed by cardiovascular drugs. An estimated cost to manage the total number of serious ADEs was approximately USD$2 billion for the older adults over the 13‐year period.

Conclusion

ADEs from PIMs occurred frequently among older adults and steadily increased over 13 years. Anticoagulants had the highest proportion of the reported ADEs and most of the ADEs were of serious outcomes including death, disabilities, and hospitalisations. The ADEs potentially incur substantial healthcare costs for this population.
The survival benefit of surgery for perihilar cholangiocarcinoma in octogenarians: Shinshu University experience
Authors: Yasukawa Koya , Shimizu Akira , Kubota Koji , Notake Tsuyoshi , Sugenoya Shinsuke , Hosoda Kiyotaka , Ikehara Tomohiko , Hayashi Hikaru , Kobayashi Ryoichiro , Soejima Yuji
Published: April 2021

Background and Objectives

In today's aging society, surgery is increasingly performed for older patients with perihilar cholangiocarcinoma (PHCC). This study aimed to examine survival and oncological outcomes in octogenarians with PHCC who underwent surgery.

Methods

We retrospectively examined 480 consecutive PHCC patients treated for PHCC between 1991 and 2020. Two hundred forty‐seven underwent resection. Patient and clinical characteristics, including postoperative complications, overall survival (OS), and disease‐free survival (DFS) were analyzed.

Results

The proportion of octogenarians with PHCC undergoing surgery increased from 5.2% in 1991–2000 to 13.4% in 2016–2020. R0 resection and postoperative complication rates were comparable between octogenarians and younger patients. Five‐year OS (30.0% vs. 31.7%) and DFS (20.0% vs. 29.5%) did not significantly differ. One‐year OS was significantly better in octogenarians who underwent resection than those who did not (95.0% vs. 17.6%; p < .001). Two octogenarians who developed Clavien–Dindo grade III complications had undergone right hemihepatectomy (RH). Posthepatectomy liver failure and biliary leakage (Grade B) were also observed in octogenarians who underwent RH.

Conclusion

In well‐selected octogenarians with PHCC, surgery offers short‐ and long‐term outcomes comparable with those of their younger counterparts. RH may be considered in octogenarians on an individual basis.
A Network Analysis of the Associations Between Posttraumatic Stress Symptoms and Posttraumatic Growth Among Disaster‐Exposed Chinese Young Adults
Authors: Yuan Guangzhe , Park Crystal L. , Birkeland Samuel R. , Yip Paul S. Y. , Hall Brian J.
Published: April 2021

Posttraumatic stress symptoms (PTSS) and posttraumatic growth (PTG) have been shown to coexist following exposure to a traumatic event, but consensus about what accounts for this association is lacking. Network analysis is a novel analytic method that can explain this linkage. In a sample of 1,809 Chinese college students (66.1% female, age range: 16–35 years) who were directly exposed to a typhoon, we investigated the network structure of PTSS and PTG, along with bridge symptoms and elements, to elucidate how distress and growth coexist. The seven strongest edges found in the model included two between elements in the PTSS cluster, one between elements of PTG, and four between elements of PTSS and PTG. Eight bridge symptoms and elements emerged: intrusive thoughts, emotional cue reactivity, hypervigilance, self‐destructive or reckless behavior, nightmares, and physiological cue reactivity among PTSS, and changed priorities and stronger religious faith among PTG elements. These findings reveal connections between PTSS and PTG that explain how these constructs may coexist in individuals exposed to natural disasters. The network perspective provides a novel way to conceptualize the association between PTSS and PTG and contributes to the field's understanding of recovery after traumatic events.
Socioeconomic Factors Affect Presentation Stage and Survival in Sinonasal Squamous Cell Carcinoma
Authors: Jafari Aria , Shen Sarek A. , Qualliotine Jesse R. , Lehmann Ashton E. , Humphreys Ian M. , Abuzeid Waleed M. , Bergmark Regan W. , Gray Stacey T.
Published: April 2021

Objectives

Socioeconomic factors affect oncologic outcome in sinonasal squamous cell carcinoma (SNSCC). However, the relationship between these factors and stage at presentation (SAP)—a critical, early point in the care cycle—is not known. This study sought to determine the role of race/ethnicity, treatment facility type, insurance status/carrier, and other socioeconomic factors in SAP and survival among patients with advanced SNSCC.

Study Design

Retrospective cohort study.

Methods

Using the National Cancer Database, 6,155 patients with SNSCC were identified and divided into those with “early” (Stage I or II; 2,212 (35.9%)) versus “advanced” (Stage III or IV; 3,943 (64.1%)) disease. Associations between sociodemographic and socioeconomic factors on SAP and survival were analyzed using multivariable logistic regression and Cox proportional hazard models.

Results

Black (odds ratio [OR]: 2.18, CI: 1.74–2.76), Asian and Pacific Islander (API) (OR: 2.37, CI: 1.43–4.14), and Medicaid or uninsured (OR: 2.04, CI: 1.66–2.53) patients were more likely to present with advanced disease. Among patients with advanced disease, API patients demonstrated the highest 10‐year survival rate (30.2%), and Black patients had the lowest 2‐, 5‐, and 10‐year survival rates (47.7%, 31.9% and 19.2%, respectively). Older age (HR:1.03, CI:1.03–1.04), Black race (HR:1.39, CI:1.21–1.59), Medicaid or uninsured status (HR:1.48, CI:1.27–1.71), and treatment at a community hospital (HR:1.25, CI:1.14–1.37) were associated with poorer overall survival among patients with advanced disease.

Conclusions

Factors including race/ethnicity, treatment facility type, insurance status/carrier, and other socioeconomic factors influence SAP and survival in SNSCC. An improved understanding of how these factors relate to outcomes may elucidate opportunities to address gaps in education and access to care in vulnerable populations.

Level of Evidence

4 Laryngoscope, 131:2421–2428, 2021
Prevalence and Risk Factors for Double Vision in Parkinson Disease
Authors: Hamedani Ali G. , Maguire Maureen G. , Marras Connie , Willis Allison W.
Published: April 2021

Background

Some patients with Parkinson Disease (PD) report double vision, but its prevalence and determinants are unknown.

Objectives

To determine the prevalence and risk factors for diplopia in PD.

Methods

Using data from 26,790 PD patients and 9257 controls in the Fox Insight Study, we compared the prevalence of diplopia using the Non‐Movement Symptom Questionnaire. Associations with age, race, gender, disease duration, and scores on MDS‐UPDRS part II, and Penn Parkinson's Daily Activity Questionnaire were assessed with generalized estimating equations.

Results

The point prevalence of diplopia was higher in PD (18.1%) than controls (6.3%, P < 0.001) at baseline, and 28.2% of all PD patients reported diplopia at least once during the study (period prevalence). PD patients with diplopia were more likely to be older, non‐white, have greater disease duration, and report greater motor, non‐motor, and daily activity limitations.

Conclusions

Diplopia is common and associates with motor and non‐motor severity in PD.
Genetic causes of preimplantation embryo developmental failure
Authors: Paonessa Mariagrazia , Borini Andrea , Coticchio Giovanni
Published: April 2021

Embryo development requires orchestrated events, finely regulated at the molecular and cellular level by mechanisms which are progressively emerging from animal studies. With progress in genetic technologies—such as genome editing and single‐cell RNA analysis—we can now assess embryo gene expression with increased precision and gain new insights into complex processes until recently difficult to explore. Multiple genes and regulative pathways have been identified for each developmental stage. We have learned that embryos with undisturbed and timely gene expression have higher chances of successful development. For example, selected genes are highly expressed during the first stages, being involved in cell adhesion, cell cycle, and regulation of transcription; other genes are instead crucial for lineage specification and therefore expressed at later stages. Due to ethical constraints, studies on human embryos remain scarce, mainly descriptive, and unable to provide functional evidence. This highlights the importance of animal studies as basic knowledge to test and appraise in a clinical context. In this review, we report on preimplantation development with a focus on genes whose impairment leads to developmental arrest. Preconceptional genetic screening could identify loss‐of‐function mutations of these genes; thereby, novel biomarkers of embryo quality could be adopted to improve diagnosis and treatment of infertility.
Proposed Standard Weight (Ws) Equations for Arctic Grayling
Authors: Gilham Andrew T. , Brown Michael L. , Jordan George R.
Published: April 2021

Relative weight (Wr) is an index that is commonly used by fisheries managers to evaluate the condition within and among fish populations. Managers also use Wr comparisons to assess condition dynamics among species. Rather than using population-level mean Wr for comparisons, standard length categories are frequently used to evaluate mean Wr differences among length categories. To establish Wr values for a species, a species-specific standard weight (Ws) equation is required. Regression-line-percentile (RLP) and empirical-percentile (EmP) methods were used with length–weight data that were collected from 50 Arctic Grayling Thymallus arcticus populations in the United States and Canada. The RLP method yielded a Ws equation of log10Ws(g) = −5.241 + 3.083 log10TL(mm) and the EmP method of log10Ws(g) = −5.279 + 3.096 log10TL(mm). These equations were developed to calculate relative weights (Wr) for fish measuring 150 mm total length (TL) and greater. Subsequent analysis did not reveal significant systematic length-related bias in the application of either Ws equation. Furthermore, differences in Ws calculations between the methods were at most 2.2% over the lengths that we observed. Our findings highlight the relative importance of using a robust data set when calculating Ws equations over the method used to calculate Ws. We suggest that both equations are valid and managers should report which Ws equation was used.
An International Continence Society (ICS) report on the terminology for pelvic floor muscle assessment
Authors: Frawley Helena , Shelly Beth , Morin Melanie , Bernard Stéphanie , Bø Kari , Digesu Giuseppe Alessandro , Dickinson Tamara , Goonewardene Sanchia , McClurg Doreen , Rahnama'i Mohammad S. , Schizas Alexis , Slieker‐ten Hove Marijke , Takahashi Satoru , Voelkl Guevara Jenniffer
Published: April 2021

Introduction

The terminology for female and male pelvic floor muscle (PFM) assessment has expanded considerably since the first PFM function and dysfunction standardization of terminology document in 2005. New terms have entered assessment reports, and new investigations to measure PFM function and dysfunction have been developed. An update of this terminology was required to comprehensively document the terms and their definitions, and to describe the assessment method and interpretation of the finding, to standardize assessment procedures and aid diagnostic decision making.

Methods

This report combines the input of members of the Standardisation Committee of the International Continence Society (ICS) Working Group 16, with contributions from recognized experts in the field and external referees. A logical, sequential, clinically directed assessment framework was created against which the assessment process was mapped. Within categories and subclassifications, each term was assigned a numeric coding. A transparent process of 12 rounds of full working group and external review was undertaken to exhaustively examine each definition, plus additional extensive internal development, with decision making by collective opinion (consensus).

Results

A Terminology Report for the symptoms, signs, investigations, and diagnoses associated with PFM function and dysfunction, encompassing 185 separate definitions/descriptors, has been developed. It is clinically based with the most common assessment processes defined. Clarity and user‐friendliness have been key aims to make it interpretable by clinicians and researchers of different disciplines.

Conclusion

A consensus‐based Terminology Report for assessment of PFM function and dysfunction has been produced to aid clinical practice and be a stimulus for research.
Denial of service detection using dynamic time warping
Authors: Diab Diab M. , AsSadhan Basil , Binsalleeh Hamad , Lambotharan Sangarapillai , Kyriakopoulos Konstantinos G. , Ghafir Ibrahim
Published: April 2021

With the rapid growth of security threats in computer networks, the need for developing efficient security‐warning systems is substantially increasing. Distributed denial‐of‐service (DDoS) and DoS attacks are still among the most effective and dreadful attacks that require robust detection. In this work, we propose a new method to detect TCP DoS/DDoS attacks. Since analyzing network traffic is a promising approach, our proposed method utilizes network traffic by decomposing the TCP traffic into control and data planes and exploiting the dynamic time warping (DTW) algorithm for aligning these two planes with respect to the minimum Euclidean distance. By demonstrating that the distance between the control and data planes is considerably small for benign traffic, we exploit this characteristic for detecting attacks as outliers. An adaptive thresholding scheme is implemented by adjusting the value of the threshold in accordance with the local statistics of the median absolute deviation (MAD) of the distances between the two planes. We demonstrate the efficacy of the proposed method for detecting DoS/DDoS attacks by analyzing traffic data obtained from publicly available datasets.