bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timerendering: reflections on chronopolitical praxis in Bolivia
Authors: Goodale Mark 
Published: June 2022

AbstractThis article uses reflections on chronopolitical praxis during the period 2006‐19 in Bolivia in order to make a more general contribution to the anthropology of time and temporalities. The article proposes the theoretical concept of ‘timerendering’ in order to examine the ways in which time emerged as a pervasive register that mediated and also deepened political, social, and ethnic conflict in Bolivia. After illustrating the mechanisms through which timerendering in Bolivia gave way to forms of allochronic denial that are described as ‘hypertemporal exclusion’, the article explains how and why the MAS government's timerendering strategies unravelled, which left it susceptible to the right‐wing coup of October/November 2019. The article concludes by narrating the endtimes of the Morales government in Bolivia, before considering what this moment and its afterlives have to say more generally about the anthropology of time as a disciplinary orientation.
Do neutrophil–lymphocyte ratio and platelet–lymphocyte ratio have a role in determining mortality in intensive care patients undergoing plasmapheresis? Single‐center experience
Authors: Sadri Sevil , Cavusoglu Gunes , Tunay Burcu 
Published: June 2022

AbstractIntroductionPlasmapheresis is a frequently used procedure that removes the pathogenic components from circulation. We aimed to evaluate the relationship between plasmapheresis, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) and mortality in the intensive care unit (ICU) between 2014 and 2021.MethodsForty‐nine patients (27 females and 22 males) were included. Demographic characteristics, laboratory values of the day of admittance to the ICU, APACHE II scores, and length of stay were recorded.ResultsThe mean age was 52.73 ± 16.93. APACHE II value (p = 0.003; p < 0.01), NLR ratio (p = 0.001; p < 0.01) and PLR ratio (p = 0.001; p < 0.01) of the surviving group were lower than those of the deceased group, which was statistically significant.ConclusionAs high PLR and NLR levels suggest increased mortality in the ICU population, attention should be paid for increased NLR and PLR when plasmapheresis is decided on in the ICU.
Using haematophagous fly blood meals to study the diversity of blood‐borne pathogens infecting wild mammals
Authors: Mwakasungula Solomon , Rougeron Virginie , Arnathau Céline , Boundenga Larson , Miguel Eve , Boissière Anne , Jiolle Davy , Durand Patrick , Msigwa Alphonce , Mswata Sarah , Olotu Ally , Sterkers Yvon , Roche Benjamin , Killeen Gerard , Cerqueira Frédérique , Bitome‐Essono Paul Yannick , Bretagnolle François , Masanja Honorati , Paupy Christophe , Sumaye Robert , Prugnolle Franck 
Published: June 2022

AbstractMany emerging infectious diseases originate from wild animals, so there is a profound need for surveillance and monitoring of their pathogens. However, the practical difficulty of sample acquisition from wild animals tends to limit the feasibility and effectiveness of such surveys. Xenosurveillance, using blood‐feeding invertebrates to obtain tissue samples from wild animals and then detect their pathogens, is a promising method to do so. Here, we describe the use of tsetse fly blood meals to determine (directly through molecular diagnostic and indirectly through serology), the diversity of circulating blood‐borne pathogens (including bacteria, viruses and protozoa) in a natural mammalian community of Tanzania. Molecular analyses of captured tsetse flies (182 pools of flies totalizing 1728 flies) revealed that the blood meals obtained came from 18 different vertebrate species including 16 non‐human mammals, representing approximately 25% of the large mammal species present in the study area. Molecular diagnostic demonstrated the presence of different protozoa parasites and bacteria of medical and/or veterinary interest. None of the six virus species searched for by molecular methods were detected but an ELISA test detected antibodies against African swine fever virus among warthogs, indicating that the virus had been circulating in the area. Sampling of blood‐feeding insects represents an efficient and practical approach to tracking a diversity of pathogens from multiple mammalian species, directly through molecular diagnostic or indirectly through serology, which could readily expand and enhance our understanding of the ecology and evolution of infectious agents and their interactions with their hosts in wild animal communities.
Nicotinamide riboside and caffeine partially restore diminished NAD availability but not altered energy metabolism in Alzheimer's disease
Authors: Ryu Woo‐In , Shen Minqi , Lee Yoon , Healy Ryan A. , Bormann Mariana K. , Cohen Bruce M. , Sonntag Kai‐Christian 
Published: June 2022

AbstractThe redox co‐factor nicotinamide adenine dinucleotide (NAD) declines with age, and NAD deficits are specifically associated with dysfunctional energy metabolism in late‐onset Alzheimer's disease (LOAD). Nicotinamide riboside (NR), a dietary NAD precursor, has been suggested to ameliorate the aging process or neurodegeneration. We assessed whether NR with or without caffeine, which increases nicotinamide mononucleotide transferase subtype 2 (NMNAT2), an essential enzyme in NAD production, modulates bioenergetic functions in LOAD. In LOAD patients—and young or old control individuals—derived dermal fibroblasts as well as in induced pluripotent stem cell‐differentiated neural progenitors and astrocytes, NR and caffeine cell type‐specifically increased the NAD pool, transiently enhanced mitochondrial respiration or glycolysis and altered the expression of genes in the NAD synthesis or consumption pathways. However, continued treatment led to reversed bioenergetic effects. Importantly, NR and caffeine did not alter the characteristics of a previously documented inherent LOAD‐associated bioenergetic phenotype. Thus, although NR and caffeine can partially restore diminished NAD availability, increasing NAD alone may not be sufficient to boost or restore energy metabolism in brain aging or alter aberrant energy management in LOAD. Nicotinamide riboside might still be of value in combination with other agents in preventive or therapeutic intervention strategies to address the aging process or age‐associated dementia.
Familial risk of postpartum depression
Authors: Rasmussen Marie‐Louise H. , Poulsen Gry J. , Wohlfahrt Jan , Videbech Poul , Melbye Mads 
Published: June 2022

AbstractObjectiveMany psychiatric diseases have a strong familial aggregation, but it is unknown whether postpartum depression (PPD) without prior psychiatric history aggregates in families.MethodsBased on Danish national registers, we constructed a cohort with information on 848,544 singleton deliveries (1996–2017). Women with an episode of PPD were defined as having used antidepressant medication and/or had a hospital contact for depression within 6 months after delivery. Those with psychiatric history prior to the delivery were excluded. We estimated relative risk (RR) of PPD, comparing women with female relatives with and without PPD history, respectively.ResultsOverall, women with a PPD history in female blood relatives had themselves a higher risk of PPD (RR = 1.64, 95% CI 1.16–2.34). Having the first‐degree female relative with PPD history was associated with a more than 2.5 times (RR = 2.65, 95% CI 1.79–3.91) increased risk of PPD. However, having the second/third‐degree female relative and/or a female non‐blood relative with PPD history did not increase the woman's own risk of PPD (RR = 0.58, 95% CI 0.26–1.28, RR = 1.09, 95% CI 0.83–1.44).ConclusionPostpartum depression aggregates in families with no other psychiatric history, but the findings do not support a strong genetic trait as a major cause. Other possible mechanisms are shared environment and/or health‐seeking behavior in close relationships.
GR‐α and GR‐β mRNA levels in peripheral blood mononuclear cells of acute myelitis patients can assist in the identification of glucocorticoid sensitivity and are correlated with glucocorticoid therapeutic effect
Authors: Tang Bolin , Han Jun , Wang Fen , Li Xiang , Zhao Chaoyang 
Published: June 2022

AbstractAcute myelitis (AM) is a rare neuro‐immune spinal cord disease. This study sought to explore the transcription level of glucocorticoid (GC) receptors α and β (GR‐α/GR‐β) in peripheral blood mononuclear cells (PBMCs) and their correlation with GC efficacy and sensitivity in AM patients. AM patients were grouped into the GC‐sensitive group (N = 80) and GC‐refractory group (N = 67). The GR‐α and GR‐β mRNA levels in PBMCs were detected. The differentiating value of GR‐α, GR‐β, and GR‐α + GR‐β on GC sensitivity and resistance in AM patients was assessed. The independent correlation between GR‐α and GR‐β mRNA levels and GC sensitivity in AM patients,t and the correlation between GR‐α and GR‐β mRNA levels and spinal function after GC treatment were analyzed. GR‐α mRNA level in PBMCs of GC‐refractory patients was lower than that of GC‐sensitive patients, while GR‐β mRNA level was higher than that of GC‐sensitive patients. GR‐α + GR‐β mRNA had a high diagnostic value for GC sensitivity and resistance in AM patients (area under the ROC curve = 0.881, sensitivity = 79.1%, specificity = 85.0%). GR‐α and GR‐β mRNA levels were independently correlated with GC sensitivity. GR‐α and GR‐β mRNA levels were correlated with the spinal function of AM patients after GC treatment. Overall, GR‐α and GR‐β mRNA levels in PBMCs of AM patients can assist in the identification of GC sensitivity and are correlated with GC efficacy.
Action guidance for addressing pollution from inhalational anaesthetics
Authors: Devlin‐Hegedus J. A. , McGain F. , Harris R. D. , Sherman J. D. 
Published: June 2022

SummaryClimate change is a real and accelerating existential danger. Urgent action is required to halt its progression, and everyone can contribute. Pollution mitigation represents an important opportunity for much needed leadership from the health community, addressing a threat that will directly and seriously impact the health and well‐being of current and future generations. Inhalational anaesthetics are a significant contributor to healthcare‐related greenhouse gas emissions and minimising their climate impact represents a meaningful and achievable intervention. A challenge exists in translating well‐established knowledge about inhalational anaesthetic pollution into practical action. CODA is a medical education and health promotion charity that aims to deliver climate action‐oriented recommendations, supported by useful resources and success stories. The CODA‐hosted platform is designed to maximise engagement of the global healthcare community and draws upon diverse experiences to develop global solutions and accelerate action. The action guidance for addressing pollution from inhalational anaesthetics is the subject of this article. These are practical, evidence‐based actions that can be undertaken to reduce the impact of pollution from inhalational anaesthetics, without compromising patient care and include: removal of desflurane from drug formularies; decommissioning central nitrous oxide piping; avoidance of nitrous oxide use; minimising fresh gas flows during anaesthesia; and prioritising total intravenous anaesthesia and regional anaesthesia when clinically safe to do so. Guidance on how to educate, implement, measure and review progress on these mitigation actions is provided, along with means to share successes and contribute to the essential, global transition towards environmentally sustainable anaesthesia.
Cloxacillin‐induced acute vanishing bile duct syndrome: A case study and literature review
Authors: Faragalla Kyrillos , Lau Helena , Wang Hanlin L. , Liu Jimin 
Published: June 2022

Ductopenia is often regarded as a chronic process where ≥50% of portal tracts lack bile ducts, which is also known as vanishing bile duct syndrome (VBDS). One aetiology is drug‐induced liver injury. Cloxacillin, an antistaphylococcal penicillin, typically causes “bland” cholestasis. We present the first case of cloxacillin‐induced acute ductopenia or VBDS and a review of published cloxacillin‐induced liver injuries. A 66‐year‐old woman with no prior liver disease, but known penicillin allergy, was treated for postcarotid angioplasty staphylococcal infection with 6 weeks of cloxacillin. She presented with a 2‐week history of weakness and jaundice. Laboratory work‐up showed elevated liver enzymes with a cholestatic pattern, hyperbilirubinemia and eosinophilia. She required ICU transfer for hypotension and was started empirically on prednisone. Liver biopsy revealed severe centrilobular cholestasis, mild necroinflammation and ductopenia with epithelial injury, but no ductular reaction. Two months later she was discharged on hydrocortisone and ursodiol with persistently elevated alkaline phosphatase and bilirubin. She was considered for liver transplantation but died of liver failure 4 months later. Four additional articles were found with histopathologic descriptions of cloxacillin‐related liver injury. These included portal inflammation, cholestasis and mild necroinflammation. Clinical features were reported in two cases; both had mild symptoms with cholestatic liver enzymes and hyperbilirubinemia. Both patients recovered completely within 10‐60 days. Cloxacillin‐induced cholestasis can be secondary to acute ductopenia, which can result in worse clinical outcomes than previously described “bland” cholestasis. Liver biopsy is recommended to identify cases with acute VBDS.
Novel serratiopeptidase exhibits different affinities to the substrates and inhibitors
Authors: Hosseinzadeh Sara Ali , Valizadeh Vahideh , Rouhani Maryam , Mirkazemi Sedigheh , Azizi Masoumeh , Norouzian Dariush , Ahangari Cohan Reza 
Published: June 2022

AbstractThe clinical application of serratiopeptidase as an anti‐biofilm and anti‐inflammatory agent is restricted due to the enzyme sensitivity to the environmental conditions. In our previous study, six enzyme variants were designed by introducing different mutations and truncations that exhibited higher thermal stability. In the present study, the interaction pattern and affinity of variants to substrates and inhibitors were studied using molecular docking and in vitro studies. CABS‐dock and Swiss‐dock servers were used for substrate (Bradykinin and Substance‐P) and inhibitor (Lisinopril and EDTA) docking, respectively. The interactions were analyzed using LigPlot, UCSF Chimera, and visual molecular dynamics packages. Free energy calculations were performed using PRODIGY. Finally, the native enzyme and the best variant in terms of interaction pattern and binding score were selected for in‐vitro affinity analysis toward Bradykinin and EDTA using HPLC and casein hydrolysis test, respectively. Molecular docking revealed that T344 [8‐339ss] variant showed a different pattern for both substrates and inhibitors in the way that none of the native active site residues were involved in the receptor binding. As revealed by in vitro studies, T344 [8‐339ss] displayed the highest number of hydrogen bond formation in docking with Bradykinin and remarkable decrement in the binding affinity for EDTA. This was the first report on the design of novel serratiopeptidase with higher activity to Bradykinin and improved resistance to EDTA as an inhibitor.
Design, synthesis, antibacterial activity evaluation and molecular docking study of pleuromutilin derivatives bearing amide side chains
Authors: Zhang Zhuo‐Qi , Liu Jie , Zhang Guang‐Yu , Li Bo , Li Kang , Jin Zhen , Bai Xu , Tang You‐Zhi 
Published: June 2022

AbstractA seize of pleuromutilin derivatives containing amide side chains were designed and synthesized as potential antibiotics against Methicillin‐resistant Staphylococcus aureus (MRSA). Among all target compounds (compounds 11–30), compound 25 was found to have the strongest antibacterial activity against MRSA (minimum inhibitory concentration = 0.5 μg/ml). The result of the time‐kill curves indicated that compound 25 could repress the growth of MRSA in vitro obviously (−3.72 log10CFU/ml reduction). Furthermore, molecular docking studies demonstrated that compound 25 was localized in the binding pocket of 50S ribosomal subunit (ΔGb = −8.99 kcal/mol). Besides, compound 25 displayed low cytotoxicity to RAW 264.7 cells. The results suggested that compound 25 might be further developed into a novel antimicrobial agent against MRSA.
Structural and dynamic investigation of non‐synonymous variations in Renin–AGT complex revealed altered binding via hydrogen‐bonding network reprogramming to accelerate the hypertension pathway
Authors: Ahmad Hussain , Khan Abbas , Umbreen Shaheena , Khan Taimoor , Xuewei Zheng , Wei Dong‐Qing , Tian Zhongmin 
Published: June 2022

AbstractHypertension is one of the major issues worldwide and one of the main factors involved in heart and kidney failure. Angiotensinogen and renin are key components of the renin–angiotensin–aldosterone system, which plays an indispensable role in hypertension. The aim of this study was to find out the non‐synonymous mutations and structure‐based mutation‐function correlation in the renin–AGT complex and reveal the most deleterious mutations to accelerated hypertension. In the current study, we employed computational modeling and molecular simulation approaches to demonstrate the impact of specific mutations in the REN‐AGT interface in hypertension. Computational algorithms, that is, PhD‐SNP, PolyPhen‐1, MAPP, Sorting Intolerant from Tolerant, Screening of non‐acceptable polymorphism, PredictSNP, PolyPhen‐2, and Protein Analysis Through Evolutionary Relationships predicted 20 mutations as deleterious in AGT while only five mutations were confirmed as deleterious in the renin protein. Investigation of the bonding analysis revealed that two mutations S107L and V193F in renin altered the hydrogen‐bonding paradigm at the interface site. Furthermore, exploration of structural‐dynamic behaviors demonstrated by that these mutations also increases the structural stability to regulate the expression of disease pathway. The flexibility index of each residues and structural compactness analysis further validated the findings by portraying the difference in the dynamic behavior in contrast to the wild type. Binding energy calculations based on molecular mechanics/generalized Born surface area methods were used which further established the binding differences between the wild type, S107L, and V193F mutant variants. The total binding energy for wild type, S107L, and V193F was reported to be −27.79, −47.72, and −38.25, respectively. In conclusion, these two mutations increase the binding free energy alongside the docking score to enhance the binding between renin and AGT to overexpress this pathway in a hypertension disease condition. Patients with these mutations may be screened for potential therapeutic intervention.
Model‐informed drug development for immuno‐oncology agonistic anti‐GITR antibody GWN323: Dose selection based on MABEL and biologically active dose
Authors: Ji Yan , Knee Deborah , Chen Xinhui , Dang Anhthu , Mataraza Jennifer , Wolf Babette , Sy Sherwin K. B. 
Published: June 2022

AbstractGWN323, an agonistic human anti‐GITR (glucocorticoid‐induced TNFR‐related protein) IgG1 antibody, was studied clinically as an immuno‐oncology therapeutic agent. A model‐based minimum anticipated biological effect level (MABEL) approach integrating in vitro and in vivo data informed dose selection for the first‐in‐human (FIH) study. Data evaluated included pharmacokinetics (PK) of DTA‐1.mIgG2a (mouse surrogate GITR antibody for GWN323), target‐engagement pharmacodynamic (PD) marker soluble GITR (sGITR), tumor shrinkage in Colon26 syngeneic mice administered with DTA‐1.mIgG2a, cytokine release of GWN323 in human peripheral blood mononuclear cells, and GITR binding affinity. A PK model was developed to describe DTA‐1.mIgG2a PK, and its relationship with sGITR was also modeled. Human GWN323 PK was predicted by allometric scaling of mouse PK. Based on the totality of PK/PD modeling and in vitro and in vivo pharmacology and toxicology data, MABEL was estimated to be 3–10 mg once every 3 weeks (Q3W), which informed the starting dose selection of the FIH study. Based on tumor kinetic PK/PD modeling of tumor inhibition by DTA‐1.mIgG2a in Colon26 mice and the predicted human PK of GWN323, the biologically active dose of GWN323 was predicted to be 350 mg Q3W, which informed the dose escalation of the FIH study. GWN323 PK from the FIH study was described by a population PK model; the relationship with ex vivo interleukin‐2 release, a target‐engagement marker, was also modeled. The clinical PK/PD modeling data supported the biological active dose projected from the translational PK/PD modeling in a “learn and confirm” paradigm of model‐informed drug development of GWN323.
Effect of limited protein consumption during the larval and adult stage on life‐history traits of the Mexican fruit fly
Authors: González‐López Gonzalo Iván , Orozco‐Dávila Dina , López‐Hernández Patricia , Díaz‐Fleischer Francisco , Alvarado‐Castillo Gerardo , Sánchez‐Viveros Gabriela , Pérez‐Staples Diana 
Published: June 2022

AbstractAnastrepha ludens Loew (Diptera: Tephritidae) is an important mango and citrus pest. The sterile insect technique (SIT) is currently used to control this fly. The SIT involves the release of sterile insects to reduce wild populations through the induction of sterility. Prior to release, insects are mass‐reared on artificial diets. The rearing of A. ludens involves the provision of protein both in the larval and adult stage, thus we studied trade‐offs between larval and adult diets. We compared various yeast concentrations in the larval diet and two formulations in the adult diet, both at small and semi‐mass scale. We determined the quality of the insects at all developmental stages. Low concentrations of torula yeast (TY) (2.9 and 3.6%) produced larvae and pupae of low weight, fewer larvae and pupae, and more males than higher TY concentrations (6.1%), but this was only discernable at a small scale. Adult survival without water and food was significantly lower for non‐irradiated males and females, and irradiated males when reared on 6.1% TY. For mating success, we found that non‐irradiated males reared on 4.8% TY but fed only sugar (S) as adults had lower probability of mating than males fed yeast hydrolysate (YH). For irradiated males, larval diet had no effect on mating competitiveness, only males fed with S + YH in the adult diet had higher mating success than those fed with S only. We propose reducing TY in the larval diet to 5.1%; however, for release colonies S + YH will need to be provided in the adult diet. Knowledge on larval and adult nutritional requirements will aid in our understanding of insect nutritional ecology and will also improve mass‐rearing diets.