bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of bird electrocution in power lines: a framework for prioritizing species and areas for conservation and impact mitigation
Authors: Biasotto L. D. , Moreira F. , Bencke G. A. , D’Amico M. , Kindel A. , Ascensão F.
Published: September 2021

Electrocution on power lines is an important human‐related cause of bird mortality and an important conservation issue worldwide. Besides impacts on bird populations, electrocutions cause power outages, resulting in damage to power line network integrity. However, there is a general lack of knowledge on the risk of bird electrocution, especially in developing countries. Generating information over large scales without resorting to local mortality data can be useful for the development of regional management strategies, particularly in countries where electrocution is poorly documented. Here, we developed a framework to model the risk of bird electrocution as an interaction between the species‐specific exposure to power lines (pole density within a species distribution range) and susceptibility (morphological and behavioral traits associated with electrocution hazards). We applied this framework to Brazil, identifying 283 species that face a risk of electrocution, of which 38 were classified as higher risk, mostly raptors (76%). The Pantanal (a large wetland biome) concentrates the greatest cumulative susceptibility due to the high number of species vulnerable to electrocution (i.e. large species using power lines for perching or nesting), while the Atlantic Forest region has a higher risk for electrocution, due to the spatial overlap between the presence of vulnerable species and high exposure to power lines. Furthermore, our study identified spatial patterns of bird electrocution, highlighting priority areas for electrocution susceptibility and electrocution risk to be further investigated, and where measures to mitigate bird electrocutions should be applied on new and existing power lines. Our framework allows a preliminary assessment aimed at identifying areas of higher risk of electrocution, to highlight species vulnerable to this threat and to improve power line routing. This approach can be replicated to other understudied areas of the world where the same information is available.
Use of maximum entropy (Maxent) niche modelling to predict the occurrence of threatened freshwater species in a biodiversity hotspot of Zimbabwe
Authors: Mafuwe Kudzai , Broadley Sheila , Moyo Sydney
Published: September 2021

Globally, freshwater species are under threat from human mediated stressors. Therefore, there is an urgent need for methods to estimate population and species occurrences for conservation purposes. Here, we used a predictive species distribution model to determine the occurrence of three endangered species (Amietia inyangae, Chlorolestes elegans and Strongylopus rhodesianus) in Southern Africa (Eastern Highlands of Zimbabwe). The study revealed that the probability of occurrences for the three species increase with an increase in elevation and annual precipitation and decrease with an increase in annual mean temperature. Our results indicated that the highest probability of occurrences for A. inyange, C. elegans and S. rhodesianus is in the Nyanga, Stapleford and Chimanimani highland areas, with some probabilities of occurrence falling outside protected areas. Our findings suggest that the areas covered by protected areas may need to be revaluated. Our findings will be useful for managing threatened species.
Birth order and socioeconomic disadvantage predict behavioural and emotional problems at age 3 years
Authors: Hjern Anders , Bergström Malin , Fransson Emma , Lindfors Anncharlotte , Bergqvist Kersti
Published: September 2021

Aim

The aim of this study was to describe sociodemographic and family predictors for behavioural and emotional problems in pre‐schoolers.

Methods

This was a cross‐sectional study including 30,795 children in the Stockholm region whose parents had completed the Strength and Difficulties Questionnaire (SDQ) prior to a routine visit to a well‐baby clinic at age 3 years. Multivariate logistic regression was used to analyse predictors for having a high total SDQ difficulties score.

Results

Young parental age and a low level of parental education predicted high total SDQ score in a stepwise pattern. Being a first‐born child was associated with a high SDQ score with an adjusted odds ratio of 2.10 (95% C.I. 1.84–2.41), compared with having older siblings. A sole physical custody arrangement predicted a high total SDQ score after parental separation. The percentage of children with a high total SDQ score increased with the Care Need Index (CNI) of the well‐baby clinic.

Conclusions

This study identified socioeconomic disadvantage and being the first‐born child as the main predictors of poor mental health at age 3 years. Well‐baby clinics with socioeconomically disadvantaged catchment areas should be provided with adequate resources and methods for equitable prevention.
Occurrence of Salmonella enterica in grey‐headed flying foxes from New South Wales
Authors: McDougall F , Power M
Published: September 2021

Salmonella enterica and Campylobacter jejuni are significant foodborne zoonotic pathogens causing gastroenteritis in humans. Domestic animals are commonly implicated as reservoirs of S. enterica and C. jejuni, but both are also detected in wild animals. Salmonella enterica serovar Typhimurium is the most common cause of human salmonellosis in Australia; however, Salmonella enterica serovar Wangata is associated with sporadic human outbreaks in New South Wales and wild animals may be a potential reservoir. To determine if wild grey‐headed flying foxes (GHFF; Pteropus poliocephalus) are reservoirs of Salmonella and Campylobacter, faecal samples were collected from three GHFF colonies in New South Wales and cultured for the presence of Salmonella and Campylobacter. One Salmonella isolate was cultured from 254 GHFF faecal samples (0.39%). Whole genome sequencing was used to genetically characterise the Salmonella isolate and perform phylogenetic analysis. The GHFF isolate was determined to be Salmonella Typhimurium ST19. The GHFF isolate carried a virulence plasmid and other virulence factors, but did not exhibit antimicrobial resistance. Phylogenetic analysis determined that the GHFF isolate was most closely related to a cluster of six isolates: four from human salmonellosis cases in Queensland and two from Australian livestock. Neither Campylobacter nor Salmonella Wangata were cultured from the 254 GHFF faecal samples. This study concluded that wild GHFF in New South Wales are not major reservoirs for Salmonella, and the zoonotic risks associated with S. enterica carriage by urban GHFF are low for the general public.
The mechanism of Epimedin B in treating osteoporosis as revealed by RNA sequencing‐based analysis
Authors: Diao Xinyue , Wang Liwen , Zhou Yating , Bi Yanan , Zhou Kun , Song Lei
Published: September 2021

With the ageing of populations, the management of osteoporosis is a priority of society in general. Epimedin B, a major ingredient of Herba Epimedii, which has the advantages of high content and hypotoxicity has been proved to be effective in preventing osteoporosis in vitro. However, the efficacy and mechanism of Epimedin B on osteoporosis in vivo have not been well elucidated yet. This study aimed to investigate the effects and the potential mechanisms of 8‐week repeated oral administration of Epimedin B (10 and 20 mg/kg/day) on a mouse osteoporosis model. Effects of Epimedin B were evaluated by examinations of serum bone turnover markers, bone mineral density, bone microstructure parameters and histopathological section. Epimedin B significantly rose N‐terminal propeptide of type I procollagen (P1NP) and dropped C‐telopeptide of type I collagen (CTX1). Connectivity density (Conn.D) increased significantly while structure model index (DA) decreased significantly after treated by Epimedin B. Meanwhile, Epimedin B administration significantly increased the number of trabecular bones while significantly decreased the gap between them. Overall, Epimedin B showed beneficial effects on osteoporosis. Furthermore, RNA sequencing‐based analysis revealed 5 significantly down‐regulated transcripts and 107 significantly up‐regulated transcripts between the Epimedin B administration group and the model group. These transcripts were mapped to 15 pathways by KEGG enrichment analysis, of which PI3K‐Akt signalling pathway, MAPK signalling pathway and PPAR signalling pathway were most connected to osteoporosis. To conclude, Epimedin B is effective in treating osteoporosis in mice via regulating PI3K‐Akt, MAPK and PPAR signalling pathway.
Decreased incidence of cesarean surgical site infection rate with hospital‐wide perioperative bundle
Authors: Sood Neha , Lee Rachel E. , To Justin K. , Cervellione Kelly L. , Smilios Maria DeMarinis , Chun Hajoon , Ngai Ivan M.
Published: September 2021

Background

Reduction in the incidence of surgical site infection (SSI) serves as a measure of patient safety and quality improvement. Cesarean birth (CB) accounts for 31.9% of all childbirths in the United States. However, our understanding of SSI prevention bundles predominantly stems from gynecological and colorectal surgeries. This study aimed to determine the efficacy of a standardized perioperative bundle designed to reduce SSI in CBs.

Methods

All CB patients at Flushing Hospital Medical Center from 2017 to 2019 were included in a retrospective analysis. Patients were divided into three groups based on the timing of intervention: prebundle/control, transition, and postbundle. Baseline demographics and clinical characteristics were summarized using descriptive statistics. Multiple logistic regression was performed to determine the association between bundle group and SSI, considering variables different between groups at baseline (P < 0.10).

Results

Two thousand eight hundred and seventy‐five CBs were performed: 1086 in prebundle, 812 in transition, and 977 in postbundle phase. In the prebundle phase, 25 CBs (2.3%) were complicated by SSIs; in the transition phase, 10 (1.2%) had SSIs; and in the postbundle phase, 7 (0.7%; P = 0.009) had SSIs. In a logistic regression model, only use of the CB bundle (OR 0.26 [95% CI 0.07‐0.94]; P = 0.04), rupture of membranes (0.29 [0.09‐0.87]; P = 0.03), and operating room time (1.02 [1.01‐1.04]; P = 0.01) were significant in prediction of SSI. SSI postbundle was significantly reduced from prebundle (0.04).

Conclusions

Thus, introduction of a hospital‐wide perioperative bundle significantly reduced SSI rates, and should be developed as a mainstay of CB surgical care.
Adoptive immunotherapy with double‐bright (CD56bright/CD16bright) expanded natural killer cells in patients with relapsed or refractory acute myeloid leukaemia: a proof‐of‐concept study
Authors: Silla Lucia , Valim Vanessa , Pezzi Annelise , da Silva Maria , Wilke Ianae , Nobrega Juliana , Vargas Alini , Amorin Bruna , Correa Bruna , Zambonato Bruna , Scherer Fernanda , Merzoni Joice , Sekine Leo , Huls Helen , Cooper Laurence J. , Paz Alessandra , Lee Dean A.
Published: September 2021

Patients with acute myeloid leukaemia (AML) have a five‐year survival rate of 28·7%. Natural killer (NK)‐cell have anti‐leukaemic activity. Here, we report on a series of 13 patients with high‐risk R/R AML, treated with repeated infusions of double‐bright (CD56bright/CD16bright) expanded NK cells at an academic centre in Brazil. NK cells from HLA‐haploidentical donors were expanded using K562 feeder cells, modified to express membrane‐bound interleukin‐21. Patients received FLAG, after which cryopreserved NK cells were thawed and infused thrice weekly for six infusions in three dose cohorts (106–107 cells/kg/infusion). Primary objectives were safety and feasibility. Secondary endpoints included overall response (OR) and complete response (CR) rates at 28–30 days after the first infusion. Patients received a median of five prior lines of therapy, seven with intermediate or adverse cytogenetics, three with concurrent central nervous system (CNS) leukaemia, and one with concurrent CNS mycetoma. No dose‐limiting toxicities, infusion‐related fever, or cytokine release syndrome were observed. An OR of 78·6% and CR of 50·0% were observed, including responses in three patients with CNS disease and clearance of a CNS mycetoma. Multiple infusions of expanded, cryopreserved NK cells were safely administered after intensive chemotherapy in high‐risk patients with R/R AML and demonstrated encouraging outcomes.
Adjuvant therapy in patients with sarcomatoid renal cell carcinoma: post hoc analysis from Eastern Cooperative Oncology Group‐American College of Radiology Imaging Network (ECOG‐ACRIN) E2805
Authors: Karam Jose A. , Puligandla Maneka , Flaherty Keith T. , Uzzo Robert G. , Matin Surena F. , Pins Michael R. , Wood Christopher G. , Kane Christopher , Jewett Michael A. S. , Kim Se Eun , Dutcher Janice P. , DiPaola Robert S. , Haas Naomi B.
Published: September 2021

Objectives

To study the effects of adjuvant therapy in patients with sarcomatoid renal cell carcinoma (sRCC) enrolled in the randomised phase III clinical trial E2805.

Patients and Methods

The original trial (E2805) was a randomised, double‐blinded phase III clinical trial comparing outcomes in 1943 patients with RCC accrued between 2006 and 2010 and treated with up to 1 year of adjuvant placebo, sunitinib, or sorafenib. The present study analyses the cohort of patients with sRCC that participated in E2805.

Results

A total of 171 patients (8.8%) had sarcomatoid features. Of these, 52 patients received sunitinib, 58 received sorafenib, and 61 received placebo. Most patients were pT3–4 (71.1%, 63.7%, and 70.5%, respectively); 17.3%, 19.0%, and 27.9% had pathologically positive lymph nodes; and 59.6%, 62.1%, and 62.3% of the patients were University of California Los Angeles (UCLA) Integrated Staging System (UISS) very‐high risk. In 49% of patients with subsequent development of metastatic disease, recurrence occurred in the lung, followed by 30% in the lymph nodes, and 13% in the liver. There was a high local recurrence rate in the renal bed (16%, 29%, and 18%, respectively). The 5‐year disease‐free survival (DFS) rates were 33.6%, 36.0%, and 27.8%, for sunitinib, sorafenib and placebo, respectively (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.45–1.20 for sunitinib vs placebo, and HR 0.82, 95% CI 0.53–1.28 for sorafenib vs placebo).

Conclusions

Adjuvant therapy with sunitinib or sorafenib did not show an improvement in DFS or OS in patients with sRCC.
Outcomes of freehand transperineal prostate biopsy with omission of antibiotic prophylaxis
Authors: Setia Shaan A. , Smith John , Cendo Demetri , Yoder Johnathan , Gorin Michael A. , Allaway Matthew J. , Vourganti Srinivas
Published: September 2021

Objective

To assess the utility of antimicrobial prophylaxis when performing freehand systematic transperineal (TP) biopsy.

Patients and Methods

From January 2012 to February 2020, freehand TP prostate biopsy via angiocatheters or the PrecisionPoint Transperineal Access System was performed on consecutive men with clinical suspicion of prostate cancer (PCa) or confirmed PCa. Biopsies were performed by a single urologist (developer of the PrecisionPoint system). Clinical data were collected retrospectively. Pre‐procedural antibiotics were given to all patients up until 6 September 2016. After this date, antibiotics were omitted from those without risk factors (chronic catherization, concurrent endoscopic procedure, history of sepsis after transrectal [TR] biopsy, history of TR biopsy within the last year, prosthetic joints/heart valves). Patients were assessed 1 week after biopsy for symptoms, emergency department visits, and hospital admissions. Patients who received antimicrobial prophylaxis were compared with those who did not, and infectious complications were analysed. Additionally, oncological outcomes were reported.

Results

A total of 988 biopsies (median prostate‐specific antigen level 7.7 ng/mL) were included in the analysis on 756 patients. Prophylaxis was given in 538 of the biopsies (54.4%) and in 450 (48.6%) it was not. There was a statistical difference in median age (67 vs 69 years; P < 0.001), abnormal digital rectal examination (13% vs 5%; P < 0.001), and history of multiparametic magnetic resonance imaging (15% vs 31%; P < 0.001) between the prophylaxis and no‐prophylaxis cohorts, respectively. There were no documented complications in those who received antibiotics. Within the no‐prophylaxis cohort, there were three (0.66%) complications (P = 0.09). Two patients (0.44%) had urinary tract infections and one patient (0.22%) experienced post‐procedural urinary retention. No patient required hospital admission or an emergency department visit. Clinically significant cancer was detected in 152 (40.0%) and 64 patients (39.0%) on initial biopsy and prior negative biopsy, respectively.

Conclusions

These data suggest that antimicrobial prophylaxis may be safely omitted in selected patients when using the freehand TP approach.
Odorant‐binding proteins of mammals
Authors: Pelosi Paolo , Knoll Wolfgang
Published: September 2021

Odorant‐binding proteins (OBPs) of vertebrates belong to the lipocalin superfamily and perform a dual function: solubilizing and ferrying volatile pheromones to the olfactory receptors, and complexing the same molecules in specialized glands and assisting their release into the environment. Within vertebrates, to date they have been reported only in mammals, apart from two studies on amphibians. Based on the small number of OBPs expressed in each species, on their sites of production outside the olfactory area and their presence in biological fluids known to be pheromone carriers, such as urine, saliva and sexual secretions, we conclude that OBPs of mammals are specifically dedicated to pheromonal communication. This assumption is further supported by the observation that some OBPs present in biological secretions are endowed with their own pheromonal activity, adding renewed interest to these proteins. Another novel piece of evidence is the recent discovery that glycosylation and phosphorylation can modulate the binding activity of these proteins, improving their affinity to pheromones and narrowing their specificity. A comparison with insects and other arthropods shows a completely different scenario. While mammalian OBPs are specifically tuned to pheromones, those of insects, which are completely different in sequence and structure, include carriers for general odorants in addition to those dedicated to pheromones. Additionally, whereas mammals adopted a single family of carrier proteins for chemical communication, insects and other arthropods are endowed with several families of semiochemical‐binding proteins. Here, we review the literature on the structural and functional properties of vertebrate OBPs, summarize the most interesting new findings and suggest possible exciting future developments.
The hydrologic classification of dilute lakes
Authors: Martin John E.
Published: September 2021

Dilute lakes, herein defined as having an electrical conductivity ≤25 µS cm−1, are considered valuable culturally, as water and recreational resources; biologically, as unique ecosystems; and scientifically, as sentinels of climate change. However, research and interest has been spread over many disciplines focusing on various issues, making hydrologic comparisons somewhat difficult. Here, 15 dilute lakes are subdivided into lake subtypes based on the dominant hydrologic input and output using annual water balance data. Dilute conditions occur in lakes dominated by all hydrologic inputs (precipitation, surface inflow, and groundwater) and outputs (evaporation, surface outflow, and groundwater), though not all possible input/output combinations produce dilute conditions. Of the nine possible hydrologic lake subtypes (three input by three output fluxes), dilute conditions have been reported in six lake subtypes, not just the traditional seepage and drainage lakes typically suggested in the literature. When annual water balance data are plotted on a “Piper‐type” graph, these six hydrologic lake subtypes are grouped into three hydrologic clusters emphasizing specific hydrologic landscape characteristics and limiting conditions hydrology may impose on naturally dilute lakes. Implications of such a classification system and possible future research questions are discussed.
Effects of the COVID‐19 pandemic on caregiver mental health and the child caregiving environment in a low‐resource, rural context
Authors: Pitchik Helen O. , Tofail Fahmida , Akter Fahmida , Sultana Jesmin , Shoab AKM , Huda Tarique M. N. , Forsyth Jenna E. , Kaushal Natasha , Jahir Tania , Yeasmin Farzana , Khan Rizwana , Das Jyoti B. , Khobair Hossain Md. , Hasan Md. Rezaul , Rahman Mahbubur , Winch Peter J. , Luby Stephen P. , Fernald Lia C. H.
Published: September 2021

Early child development has been influenced directly and indirectly by the COVID‐19 pandemic, and these effects are exacerbated in contexts of poverty. This study estimates effects of the pandemic and subsequent population lockdowns on mental health, caregiving practices, and freedom of movement among female caregivers of children 6–27 months (50% female), in rural Bangladesh. A cohort (N = 517) was assessed before and during the pandemic (May–June, 2019 and July–September, 2020). Caregivers who experienced more food insecurity and financial loss during the pandemic reported larger increases in depressive symptoms (0.26 SD, 95% CI 0.08–0.44; 0.21 SD, 0.04–0.40) compared to less affected caregivers. Stimulating caregiving and freedom of movement results were inconsistent. Increases in depressive symptoms during the pandemic may have consequences for child development.
Diagnostic yield of genetic testing in 324 infants with hypotonia
Authors: Sharma Sonal , Repnikova Elena , Noel‐MacDonnell Janelle R. , LePichon Jean‐Baptiste
Published: September 2021

This retrospective cohort study was designed to determine the yield of genetic tests in hypotonic infants and develop a diagnostic algorithm. Out of 496 patients identified by International Classification of Diseases (ICD) 9/10 coding, 324 patients met the inclusion criteria. Diagnostic yields were 32% for karyotype, 19% for microarray, 30% for targeted genetic tests, 38% for gene panels, and 31% for exome sequencing. In addition, we considered the diagnostic contribution of ancillary tests, including neuroimaging, metabolic tests, and so forth. The combination of microarray and exome sequencing gave the highest diagnostic yield. None of the other tests added significant value in arriving at a diagnosis. Based on these results we propose that the vast majority of infants with congenital hypotonia should start with a microarray and proceed with exome sequencing, with the notable exception of infants with clearly syndromic features in whom karyotyping or targeted testing may be more appropriate.
Disruption of rack1 suppresses SHH‐type medulloblastoma formation in mice
Authors: Liu Fengjiao , Shao Jingyuan , Yang Haihong , Yang Guochao , Zhu Qian , Wu Yan , Zhu Lingling , Wu Haitao
Published: September 2021

Introduction

Medulloblastoma (MB) is a malignant pediatric brain tumor that arises in the cerebellar granular neurons. Sonic Hedgehog subtype of MB (SHH‐MB) is one of the major subtypes of MB in the clinic. However, the molecular mechanisms underlying MB tumorigenesis are still not fully understood.

Aims

Our previous work demonstrated that the receptor for activated C kinase 1 (Rack1) is essential for SHH signaling activation in granule neuron progenitors (GNPs) during cerebellar development. To investigate the potential role of Rack1 in MB development, human MB tissue array and SHH‐MB genetic mouse model were used to study the expression of function of Rack1 in MB pathogenesis.

Results

We found that the expression of Rack1 was significantly upregulated in the majority of human cerebellar MB tumors. Genetic ablation of Rack1 expression in SHH‐MB tumor mice could significantly inhibit MB proliferation, reduce the tumor size, and prolong the survival of tumor rescue mice. Interestingly, neither apoptosis nor autophagy levels were affected in Rack1‐deletion rescue mice compared to WT mice, but the expression of Gli1 and HDAC2 was significantly decreased suggesting the inactivation of SHH signaling pathway in rescue mice.

Conclusion

Our results demonstrated that Rack1 may serve as a potential candidate for the diagnostic marker and therapeutic target of MB, including SHH‐MB.
Federalism, but how? The impact of vertical fiscal imbalance on economic growth. Evidence from Belgium*
Authors: Mitra Alessio , Chymis Athanasios
Published: September 2021

This paper applies both parametric and nonparametric synthetic control methods in the case of a specific federal reform. It evaluates the impact of Belgium's constitutional federalism reform of 1993 on GDP per capita. The findings show a negative impact of the reform on economic growth. This negative impact ceases soon after 2001, when a subsequent reform reduced the vertical fiscal imbalance that characterized the 1993 federal reform. It is argued that the presence of a strong federalism with subnational spending autonomy and, conversely, a centralized tax system, enhanced pork barrel spending, a common pool problem, thus damaging economic growth.
Protons to Patients: targeting endosomal Na+/H+ exchangers against COVID‐19 and other viral diseases
Authors: Prasad Hari
Published: September 2021

While there is undeniable evidence to link endosomal acid‐base homeostasis to viral pathogenesis, the lack of druggable molecular targets has hindered translation from bench to bedside. The recent identification of variants in the interferon‐inducible endosomal Na+/H+ exchanger 9 associated with severe coronavirus disease‐19 (COVID‐19) has brought a shift in the way we envision aberrant endosomal acidification. Is it linked to an increased susceptibility to viral infection or a propensity to develop critical illness? This review summarizes the genetic and cellular evidence linking endosomal Na+/H+ exchangers and viral diseases to suggest how they can act as a broad‐spectrum modulator of viral infection and downstream pathophysiology. The review also presents novel insights supporting the complex role of endosomal acid‐base homeostasis in viral pathogenesis and discusses the potential causes for negative outcomes of clinical trials utilizing alkalinizing drugs as therapies for COVID‐19. These findings lead to a pathogenic model of viral disease that predicts that nonspecific targeting of endosomal pH might fail, even if administered early on, and suggests that endosomal Na+/H+ exchangers may regulate key host antiviral defence mechanisms and mediators that act to drive inflammatory organ injury.
Migrasome biogenesis and functions
Authors: Yu Shunbang , Yu Li
Published: September 2021

The migrasome is a newly discovered organelle produced by migrating cells. As cells migrate, long and thin retraction fibers are left in their wake. On these fibers, we discovered the production of a pomegranate‐like structure, which we named migrasomes. The production of migrasomes is highly correlated with the migration of cells. Currently, it has been demonstrated the migrasomes exhibit three modes of action: release of signaling molecules through rupturing or leaking, carriers of damaged mitochondria, and lateral transfer of mRNA or proteins. In this review, we would like to discuss, in detail, the functions, mechanisms, and potential applications of this newly discovered cell organelle.
Crosstalk between protein kinase A and the HOG pathway under impaired biosynthesis of complex sphingolipids in budding yeast
Authors: Urita Atsuya , Ishibashi Yohei , Kawaguchi Ryotaro , Yanase Yukimi , Tani Motohiro
Published: September 2021

Complex sphingolipids are important components of the lipid bilayer of budding yeast Saccharomyces cerevisiae, and a defect of the biosynthesis causes widespread cellular dysfunction. In this study, we found that mutations causing upregulation of the cAMP/protein kinase A (PKA) pathway cause hypersensitivity to the defect of complex sphingolipid biosynthesis caused by repression of AUR1 encoding inositol phosphorylceramide synthase, whereas loss of PKA confers resistance to the defect. Loss of PDE2 encoding cAMP phosphodiesterase or PKA did not affect the reduction in complex sphingolipid levels and ceramide accumulation caused by AUR1 repression, suggesting that the change in sensitivity to the AUR1 repression due to the mutation of the cAMP/PKA pathway is not caused by exacerbation or suppression of the abnormal metabolism of sphingolipids. We also identified PBS2 encoding MAPKK in the high‐osmolarity glycerol (HOG) pathway as a multicopy suppressor gene that rescues the hypersensitivity to AUR1 repression caused by deletion of IRA2, which causes hyperactivation of the cAMP/PKA pathway. Since the HOG pathway has been identified as one of the rescue systems against the growth defect caused by the impaired biosynthesis of complex sphingolipids, it was assumed that PKA affects activation of the HOG pathway under AUR1‐repressive conditions. Under AUR1‐repressive conditions, hyperactivation of PKA suppressed the phosphorylation of Hog1, MAPK in the HOG pathway, and transcriptional activation downstream of the HOG pathway. These findings suggested that PKA is possibly involved in the avoidance of excessive activation of the HOG pathway under impaired biosynthesis of complex sphingolipids.
Post Audit of Simulated Groundwater Flow to a Short‐Lived (2019 to 2020) Crater Lake at Kīlauea Volcano
Authors: Flinders Ashton F. , Kauahikaua James P. , Hsieh Paul A. , Ingebritsen Steven E.
Published: September 2021

About 14.5 months after the 2018 eruption and summit collapse of Kīlauea Volcano, Hawaiʻi, liquid water started accumulating in the deepened summit crater, forming a lake that attained 51 m depth before rapidly boiling off on December 20, 2020, when an eruption from the crater wall poured lava into the lake. Modeling the growth of the crater lake at Kīlauea summit is important for assessing the potential for explosive volcanism. Our current understanding of the past 2500 years of eruptive activity at Kīlauea suggests a slight dominance of explosive behavior over effusive. The deepened summit crater and presence of the crater lake in 2019 raised renewed concerns about explosive activity. Groundwater models using hydraulic‐property data from a nearby drillhole successfully forecast the timing and rate of lake filling. Here we compare the groundwater‐model predictions with observational data through the demise of the crater lake, examine the implications for local water‐table configuration, consider the potential role of evaporation and recharge (neglected in previous models), and briefly discuss the energetics of the rapid boil‐off. This post audit of groundwater‐flow models of Kīlauea summit shows that simple models can sometimes be used effectively to simulate complex settings such as volcanoes.
Low immunogenicity of emicizumab in persons with haemophilia A
Authors: Schmitt Christophe , Emrich Thomas , Chebon Sammy , Fernandez Elena , Petry Claire , Yoneyama Koichiro , Kiialainen Anna , Howard Monet , Niggli Markus , Paz‐Priel Ido , Chang Tiffany
Published: September 2021

Introduction

Emicizumab is a humanised, bispecific monoclonal antibody mimicking the cofactor function of activated factor (F)VIII. It is indicated for routine prophylaxis of bleeding episodes in persons with haemophilia A (PwHA) with/without FVIII inhibitors.

Aim

To evaluate the development of anti‐emicizumab antibodies and their impact on pharmacokinetics (PK), pharmacodynamics (PD), efficacy and safety in PwHA.

Methods

Data from seven completed or ongoing phase 3 studies were pooled. The assessment of the immunogenicity profile of emicizumab included anti‐drug antibody (ADA) measurement and the association of ADAs with PK, PD, bleeding events, and adverse events.

Results

Of 668 PwHA evaluable for immunogenicity analysis, 34 (5.1%) developed ADAs after exposure to emicizumab. ADAs were transient in 14/34 PwHA (41.2%). ADAs were neutralising in vitro in 18/34 PwHA (52.9%) and associated with decreased emicizumab concentration in 4/668 evaluable PwHA (.6%); of those, one (.1%) discontinued emicizumab due to loss of efficacy. ADAs without decreased exposure did not impact emicizumab efficacy. The proportion of PwHA who had injection‐site reactions (ISRs) was higher in ADA‐positive PwHA (29.4% vs. 20.8%); however, the safety profile was similar between ADA‐positive and ADA‐negative PwHA, overall. No cases of anaphylaxis or hypersensitivity were reported in ADA‐positive participants.

Conclusion

The immunogenicity risk of emicizumab in phase 3 studies was low. ADAs, including in vitro neutralising ADAs, were not associated with a change in safety profile. Routine surveillance is, therefore, not warranted; however, in cases where a loss and/or waning of efficacy are observed, prompt evaluation by a healthcare provider should be sought.
Women and girls with haemophilia receiving care at specialized haemophilia treatment centres in the United States
Authors: Miller Connie H. , Soucie J. Michael , Byams Vanessa R. , Payne Amanda B. , Sidonio Robert F. , Buckner Tyler W. , Bean Christopher J.
Published: September 2021

Introduction

Females may have haemophilia with the same factor VIII (FVIII) or factor IX (FIX) levels as affected males. Characterization of females with haemophilia would be useful for health care planning to meet their unique needs. Federally‐funded haemophilia treatment centres (HTCs) in the United States contribute data on all individuals with bleeding disorders receiving care to the Population Profile (HTC PP) component of the Community Counts Public Health Surveillance of Bleeding Disorders project.

Aims

To estimate the number of females with haemophilia receiving care at HTCs in the United States and compare their characteristics with those of males with haemophilia.

Methods

HTC PP data collected on people receiving care at an HTC from January 2012 through September 2020 with haemophilia A and B were evaluated by sex for demographic and clinical characteristics.

Results

A factor level < 40% was reported for 23,196 males (97.8%) and 1667 females (47.6%) attending HTCs; 51 (.48%) severe, 79 (1.4%) moderate, and 1537 (17.9%) mild haemophilia patients were female. Females were older, more often White, and less often non‐Hispanic than males. Females were less likely to have history of HIV or HCV infection, even among those with severe disease, but twice as likely to have infection status unknown. Females with mild haemophilia were more often uninsured than males.

Conclusions

Females with severe or moderate haemophilia are uncommon, even in specialized care centres; however, almost one in five patients with mild haemophilia was female, indicating needs for specialized care based on factor level and history for affected females.
Changes of static and dynamic spine alignment in patients with severe haemophilia
Authors: Hmida Jamil , Hilberg Thomas , Krüger Steffen , Jansen Tom R. , Goldmann Georg , Oldenburg Johannes , Wirtz Dieter C. , Strauss Andreas C.
Published: September 2021

Introduction

Haemophilic arthropathy results in a restricted range of motion and pain that often affects gait. The effect of these gait changes on spinal posture has not been studied.

Aim

To evaluate whether the altered joint situation in patients with haemophilia (PwH) leads to compensatory mechanisms evident in the trunk and spine, considering static and dynamic conditions.

Methods

PwH and healthy controls (20–65 years) were examined using rasterstereography in a controlled cohort study. Analysis was performed in static and dynamic conditions in regard to gait phases. Joint status was determined using the Haemophilia Joint Health Score (HJHS).

Results

Static measurements showed no group differences in PwH (n = 40) compared to healthy controls (n = 40) except pelvic torsion (median [25%‐quartile;75%‐quartile]: ‐1.9[‐3.2;.9]° vs. .5[‐1.1;1.9]°; P = .007). In contrast, under dynamic conditions PwH showed significantly higher trunk inclination and lower apex lumbar lordosis in all gait phases. Additionally, pelvic torsion was increased in mid stance and terminal swing. Considering joint status, PwH had a higher global HJHS (23.5[13.0;30.0] vs. 3.0[1.0;5.0]; P<.001). A significant moderate correlation was shown between the HJHS mobility score and spine parameters (r = .228–.588; P<.05).

Conclusion

Degenerative joint changes in PwH lead to altered spine posture during gait. A reason could be the reduced mobility in the affected joint. Changes in spinal and pelvic posture lead to higher structural burdens; therefore, clinicians should focus on posture of spinal column during gait in daily treatment.
COVID‐19 information seeking needs and behaviour among citizens in Isfahan, Iran: A qualitative study
Authors: Soleymani Mohammad Reza , Esmaeilzadeh Maedeh , Taghipour Faezeh , Ashrafi‐rizi Hasan
Published: September 2021

Background

Access to reliable and credible health information improves individuals’ personal care level in crises, such as the coronavirus disease 2019 (COVID‐19) pandemic. It subsequently results in enhancing the community's health and reducing the health system's costs.

Objectives

This study aimed to investigate the COVID‐19 related information seeking behaviour demonstrated by citizens in Isfahan, Iran.

Methods

This research was conducted in 2020 and employed a qualitative approach using conventional content analysis. The research population was selected from almost different social classes of people in Iran using purposive sampling. The saturation point was reached at 24 semi‐structured interviews. The data's soundness was confirmed based on the criteria of credibility, confirmability, dependability and transferability proposed by Guba and Lincoln.

Results

The findings revealed five subcategories and 25 codes within the information seeking behaviour. The subcategories included attitude towards the COVID‐19 crisis, information needs, information resources, information validation and information seeking barriers.

Conclusion

People seek information from various resources to update their knowledge and become more prepared in the face of COVID‐19. The findings can be used to develop policies on informing and preventing the dissemination of false information in crises, such as the COVID‐19 crisis.
1. CHASING INDIA IN MEXICO CITY
Authors: ZAMAN TAYMIYA R.
Published: September 2021

A paradox informs the writing of Mexican and Indian history. In Malintzin's Choices: An Indian Woman in the Conquest of Mexico (2006), Camilla Townsend writes that Mexico was conquered and could never be conquered because indigenous ways of being in the world survived, adapted, and continued. Similarly, in A Book of Conquest: The Chachnama and Muslim Origins in South Asia (2016), Manan Ahmed Asif writes that Sindh was conquered by British armies but cities such as Uch, in which shrines and trees remain imbued with the sacred, point to that which is impossible to conquer. If change itself has unchanging essence embedded within it (we must know what Sindh or Mexico are in order to recognize that they have changed), then what would it mean for postcolonized historians to think more deeply about what historical narrative cannot conquer, tame, or control? How might we think about ways of doing history that we have internalized despite these being products of European conquest themselves? To reflect on these questions, I draw on my forays into Mexican history as a Mughal historian and discuss how examining premodern and modern encounters between the Muslim world and the Americas might open windows into unexplored ways of inhabiting the past and present.
2. READING ACROSS FIRISHTA AND CHIMALPAHIN
Authors: ASIF MANAN AHMED
Published: September 2021

In this essay, I reflect on the position of a postcolonized historian traversing space and time, thinking and linking to histories of European arrivals to Mexico and India. The essay is concerned with early seventeenth‐century histories by Chimalpahin and Firishta, who documented their worlds before and after the arrival of Europeans. I argue for a transregional decolonial approach to thinking about historical violence and the formation of disciplinary histories.
3. RESPONSES FROM LATIN AMERICA: THOUGHTS OF A CONTEMPORARY SCHOLAR AND OF THE SEVENTEENTH‐CENTURY INDIGENOUS HISTORIAN CHIMALPAHIN
Authors: TOWNSEND CAMILLA
Published: September 2021

This essay is a response to this forum's other two essays, which are by Taymiya R. Zaman and Manan Ahmed Asif. In it, I share in the excitement presently generated in the field of history by the effort to make South‐South connections and yet also warn of the inherent limitations of such efforts. Subaltern studies famously failed to take hold among Latin Americanists, largely because the colonial context there was so profoundly different than in South Asia that it failed to illuminate history in the same ways. I assert that what Zaman and Asif attempt to do in their essays differs significantly from what subaltern studies scholars have done because they visit Latin America, literally and figuratively, in order to foster new lines of thinking in their writings about Asia. In response, I begin by considering what forays into Asia would likely do for the study of Mexico. Then, to test the forum contributors' modern assumptions about the usefulness of such efforts, I consider what Chimalpahin, the greatest of the colonial Nahua historians, revealed about his own interest in using the notion of Asia to think with.
CATASTROPHE NOW
Authors: Catlin Jonathon
Published: September 2021

Literary scholar Eva Horn's The Future as Catastrophe: Imagining Disaster in the Modern Age investigates why modern Western culture so often imagines its own end. Through insightful readings of modern literature, film, and philosophical and sociological discourses, Horn argues that our hunger for apocalypse narratives—chief among them those about the so‐called Last Man—is rooted in a deep‐seated but diffuse mood of risk and crisis that has been generated by contingent and often imperceptible threats, such as impending nuclear disaster and climate change. Without concrete events to anchor it, this anxiety grows and paralyzes action. Representing these possible catastrophes through fiction provides us with cathartic, vivid, and plausible depictions of discrete events. Imagining such scenarios also serves as a practical means of preparing ourselves individually and collectively for possible threats, in turn helping to make them self‐defeating prophecies. One of Horn's central claims is that fiction's capacity to imagine and capture affect, nuance, and detail offers a uniquely powerful means of thinking about the future. This essay challenges that position by arguing that fiction (though it is, as Donna J. Haraway has quipped, often the best political theory) on its own lacks the capacity for critique that connects imagined future catastrophes to their latent causes in presently catastrophic social conditions. Horn illustrates that imagined future catastrophes often illuminate the latent vulnerabilities of the societies that produced them, but her focus on apocalyptic scenarios reproduces, rather than challenges, cultural patterns that obscure more quotidian and destructive forms of “slow violence” and “slow disaster.” If historians and critics are to achieve the consciousness of catastrophic threats against which Horn seeks to mobilize apocalypse fiction, such narratives must also be folded back into a critical history of the present that asks a more pointed political question: for whom is life already catastrophic?
Prevalence of filaggrin loss‐of‐function variants in Chilean population with and without atopic dermatitis
Authors: Cárdenas Geovanna V. , Iturriaga Carolina , Hernández Caroll D. , Tejos‐Bravo Macarena , Pérez‐Mateluna Guillermo , Cabalin Carolina , Urzúa Marcela , Venegas‐Salas Luis F. , Fraga Juan P. , Rebolledo Boris , Poli Maria C. , Repetto Gabriela M. , Casanello Paola , Castro‐Rodríguez José A. , Borzutzky Arturo
Published: September 2021

Background

Filaggrin (FLG) loss‐of‐function variants are major genetic risk factors for atopic dermatitis (AD), but these have not been studied in Latin American populations with and without AD.

Methods

FLG variants R501X and 2282del4 were genotyped in 275 Chilean adults with and without AD from the “Early origins of allergy and asthma” (ARIES) cohort and in 227 patients from an AD cohort based in Santiago, Chile.

Results

Among adults in the ARIES cohort, 3.3% were carriers of R501X and 2.9% of 2282del4 variants, all heterozygotes. In this cohort, 6.2% were FLG variant carriers: 11.1% of subjects reporting AD were carriers of FLG variants vs. 5.2% in those without AD (P = 0.13). In this first cohort, FLG variants were not significantly associated with asthma, allergic rhinitis, or food allergy. In the AD cohort, the prevalence of FLG variants was 7% for R501X, 2.2% for the 2282del4 variant, and 9.3% for the combined genotype. In this cohort, FLG variants were present in 15.5% of severe AD vs. 7.1% of mild‐to‐moderate AD subjects (P = 0.056). Evaluation of Chilean population from both cohorts combined (n = 502) revealed that FLG variants were not significantly associated with AD (OR = 1.92 [95% CI 0.95–3.9], P = 0.067) but were associated with asthma (OR = 2.16 [95% CI 1.02–4.56], P = 0.039).

Conclusions

This is the first study to evaluate FLG loss‐of‐function variants R501X and 2282del4 in Latin American population, revealing a similar prevalence of these FLG variant carriers to that of European populations. Among Chileans, FLG variants were significantly associated with asthma but not AD.
Beyond street‐level bureaucracy: the organisational culture of migration policy‐making and administrative elites
Authors: Wakisaka Daisuke
Published: September 2021

Migration policies are shaped by multiple actors, including politicians, business sectors, civil society and the courts. Literature has to date elucidated the role and agency of each of these actors in order to theorize the policy‐making process and its interplay with the lives of migrants. Nevertheless, the institutional functions of government officials, namely bureaucrats, have been significantly understudied, although they are the primary decision‐makers in framing and implementing regulations. Drawing on in‐depth qualitative research conducted in Japan, this article sheds light on the organizational culture of administrative elites in designing migration policies. The findings show that human resource practices and organizational positions predicate risk averse behaviour, consequently limiting the development of innovative policies. The paper finally argues that a paradigm shift in migration policy‐making is required in tackling the communal challenges of wealthy states.
Psychological disorder diagnosis is no cure for trait inferences bias
Authors: Jacinto Sofia , Braga João Niza , Ferreira Marina Silva , Collins Elizabeth C. , Krendl Anne C. , Lewis Cara C.
Published: September 2021

According to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, maladaptive behavior stemming from a psychological disorder should not be attributed to personality. Attribution of behavioral symptoms to personality may undermine treatment‐seeking and therapy outcomes and increase the stigmatization of the mentally ill. Although people adjust dispositional inferences given contextual alternative causes, we propose that beliefs in the stability and controllability of mental illness could lead to confounded representations of personality and psychological disorders. In six studies we tested whether people adjust dispositional inferences given a psychological disorder as they do give a physical impairment. Participants made trait ratings from short behavioral descriptions and corresponding contextual accounts. When the putative cause for the behavior was a psychological disorder, people did not reduce the trait inference to the extent they did when the cause was a physical impairment, except when the psychological disorder was presented as controllable/unstable. This suggests a conflation of psychological disorders with personality.