bluuebunny/crossref_metadata_2025 huggingface dataset:
Food geographies ‘in’, ‘of’ and ‘for’ the Anthropocene: Introducing the issue and main themes
Authors: Maye Damian , Coles Ben , Evans David
Published: May 2022

The Anthropocene provides a useful way to think through all manner of human–environment processes and challenges. This is especially pronounced in relation to food and farming, which are heavily implicated in changes to the Earth's biophysical and chemical processes. Yet, despite burgeoning interest in the Anthropocene as a concept, it is comparatively absent from recent developments in food geography. This is surprising given the profound impacts of food and agriculture on biogeochemical flows and geographical strata, and given future predictions regarding ‘Anthropogenic climate change.’ The objective of this Theme Issue therefore, and the five papers that comprise it, is to redress this by directly connecting and drawing together social science scholarship that examines food geographies ‘in,’ ‘of’ and ‘for’ the Anthropocene. The Theme Issue papers engage with different aspects of the Anthropocene as spatial phenomena and here we integrate relevant arguments from each, alongside wider agri‐food geographical scholarship, to explain what we mean by food geographies ‘in,’ ‘of’ and ‘for’ the Anthropocene. In doing so, we respond to Tsing and colleagues' (2019, Current Anthropology 60, S186–97) call for a spatial as well as temporal treatment of the Anthropocene. These spatial expressions are also key to the proliferation of terms that have accompanied developments in Anthropocene scholarship. We conclude by offering up some brief reflections on a future research agenda. An important first step is to conceptualise food geographies ‘in,’ ‘of’ and ‘for’ the Anthropocene, including accounts that ground and potentially unsettle food and the Anthropocene as Capitalocene (Moore, 2016, Anthropocene or Capitalocene? Nature, history, and the crisis of capitalism) and food and the Anthropocene as more‐than‐human (Haraway, 2016, Staying with the trouble: Making kin in the Chthulucen). A second step is to address key contemporary Anthropogenic agri‐food relations, especially those that are already in flux or transition. A final priority for future research is to deepen and extend the ethics of care and moral food geographies of the Anthropocene imperative.
The legacy of haemophilia: Memories and reflections from three survivors
Authors: Farrugia Albert , Smit Cees , Buzzi Andrea
Published: May 2022

Following the publication of a book of personal memories by one of us (CS1,2), we have attempted to synthesis our joint memories of three ageing men, born in the era preceding universal access to treatment, in an attempt to describe our experience, our challenges and our reflections on the development of therapies, which have ensured that our experience of growing up with haemophilia in the 1950s and 1960s has not been mirrored by the current generation of patients. We describe our upbringing in different parts of Europe in health care systems which, while of varying standards, were all unable to offer the kind of care which developed after the development of specific therapies. We assess the effect of the contamination of these therapies by blood‐borne pathogens on our own development, and the development of our communities around us. In addition, we reflect on the lessons learnt, sometimes painfully, by our generation of people with haemophilia and how some of these enabled us to overcome substantial hurdles, survive and build productive lives. Finally, we survey the development of therapies in the past 20 years, and offer some reflections on how our experience can be integrated in a realistic expectation of what the future holds for our community, in our own affluent societies and in countries less advantaged economically. We hope that our thoughts may contribute to continued progress in the field of haemophilia care.
Lean/normal‐weight metabolic dysfunction‐associated fatty liver disease is a risk factor for reflux esophagitis
Authors: Fukunaga Shuhei , Nakano Dan , Tsutsumi Tsubasa , Kawaguchi Takumi , Eslam Mohammed , Yoshinaga Shinobu , Abe Hirohiko , Nouno Ryuichi , Joh Seiya , Mitsuyama Keiichi , George Jacob , Torimura Takuji
Published: May 2022

Aim

Reflux esophagitis is associated with metabolic dysfunction. Recently, fatty liver has been redefined as metabolic dysfunction‐associated fatty liver disease (MAFLD). We investigated the impact of MAFLD and its subtypes on the incidence of reflux esophagitis.

Methods

This multicenter, observational cohort study enrolled 9100 consecutive health‐check examinees who underwent esophagogastroduodenoscopy and ultrasonography. All patients were classified into the MAFLD or non‐MAFLD group. Based on the Asian cut‐off value for body mass index (BMI), the MAFLD group was further classified into the lean/normal‐weight (BMI <23 kg/m2) and overweight/obese (BMI ≥23 kg/m2) subgroups. The impact of MAFLD and its subtypes on the cumulative incidence of reflux esophagitis was evaluated using multivariable Cox proportional hazards regression analysis.

Results

MAFLD was diagnosed in 26.5% (2416/9100) of patients. Multivariable Cox proportional hazards regression analysis indicated that MAFLD (hazard ratio [HR] 1.2183; 95% confidence interval [CI] 1.0954–1.3550; p = 0.0003), hiatal hernia, and aging were independent risk factors for reflux esophagitis. Stratification analysis indicated that cumulative incidence of reflux esophagitis among patients with MAFLD was significantly higher in the lean/normal‐weight than in the overweight/obese group (HR 1.3274; 95% CI 1.0043–1.7547; p = 0.0466). Among various metabolic factors, visceral adiposity was the only independent metabolic risk factor for reflux esophagitis (HR 2.8331; 95% CI 1.0201–7.8691; p = 0.0457) in the lean/normal‐weight MAFLD group.

Conclusions

MAFLD, in particular lean/normal‐weight MAFLD, is independent risk factor for reflux esophagitis. Furthermore, visceral adiposity was identified as the most strong metabolic risk factor for reflux esophagitis in lean/normal‐weight patients with MAFLD.
Preclinical 3D‐printed laboratory simulation of deep caries and the exposed pulp reduced student anxiety and stress, while increasing confidence and knowledge in vital pulp treatment
Authors: Chevalier Valérie , Dessert Marjolaine , Fouillen Kevin John , Lennon Sile , Duncan Henry Fergus
Published: May 2022

Aim

To evaluate the impact of a preclinical laboratory session using 3D printed teeth on dental student stress, anxiety, confidence and knowledge when treating deep caries and pulp exposure.

Methodology

This was a two‐centre controlled study, with randomized distribution of students into two groups: a vital pulp treatment (VPT) lecture‐only (control) group and a VPT‐lecture combined with a VPT‐laboratory (experimental) group. In both universities, preclinical students with endodontic or operative dentistry laboratory sessions could participate. All students were invited to the lecture. Two weeks later (timepoint‐T1), both groups completed validated and bespoke questionnaires and scales to evaluate their stress (Stress‐VAS), anxiety (STAI Trait [T] and State [S]), self‐confidence and knowledge. Thereafter, only the experimental group attended the hands‐on laboratory session demonstrating the techniques of selective caries removal and partial pulpotomy on a commercial 3D‐printed tooth. Two weeks later (timepoint‐T2), the participants from both groups repopulated the same questionnaires and VAS. The control group had the laboratory session after the completion of the study. The statistical analysis was performed with Statistica® (significance p = .05). The homogeneity between the two samples was checked by Khi2 and Student tests. Stress‐VAS, STAI‐S, confidence and knowledge scores were compared within each group, and between the two groups, at T1 and T2, with a repeated measures anova test (+/−Tukey post‐hoc test).

Results

The groups comprised 54 students each, with no statistical difference between the groups regarding demographic, academic data and STAI‐T score. The two groups had no significant difference of Stress‐VAS, STAI‐S, confidence and knowledge scores at T1 while they presented a significant difference in stress, anxiety and confidence scores at T2, but with no significant difference in knowledge score. However, knowledge score, as other parameters, improved significantly between T1 and T2 in the experimental group.

Conclusions

The addition of a laboratory session using 3D‐printed teeth that simulated deep caries and pulp exposure management, significantly reduced the stress and anxiety of students and increased their confidence. Within the limitations of this study, the benefit of introducing new technology in increasing student confidence and reducing stress offers opportunity for educational improvement in the VPT and cariology areas.
Sodium butyrate reverses lipopolysaccharide‐induced mitochondrial dysfunction in lymphoblasts
Authors: Weiss Scott L. , Zhang Donglan , Farooqi Sumera , Wallace Douglas C.
Published: May 2022

Butyrate is a short‐chain fatty acid that is produced by commensal microbes within the intestinal microbiome through fermentation of dietary fibre. Microbial‐derived butyrate has been shown to promote immunologic and metabolic homeostasis, in part through its beneficial effects on mitochondrial function, and thus has been proposed as a possible anti‐inflammatory therapy. We tested the hypothesis that butyrate could mitigate the decrease in mitochondrial respiration in immune cells under septic conditions as a preliminary step towards better understanding the potential for butyrate as a novel therapy in sepsis. Mitochondrial respiration and content (measured as citrate synthase activity) were compared within four Epstein–Barr virus‐transformed lymphoblast (LB) cell lines exposed to either control media or lipopolysaccharide (LPS) 100 ng/ml. Both co‐incubation of LBs with LPS + butyrate and treatment with butyrate after LPS stimulation reversed the decrease in mitochondrial respiration observed in LBs exposed to LPS without butyrate. Neither LPS nor butyrate led to significant changes in citrate synthase activity. The preliminary findings support further investigation of a potential mitochondrial‐based mechanism through which butyrate may help to mitigate the immuno‐inflammatory response in sepsis.
High prevalence of depressive symptoms among people with pediatric‐onset and adolescent‐onset type 1 diabetes: A cross‐sectional analysis of the Diabetes Study from the Center of Tokyo Women's Medical University
Authors: Takaike Hiroko , Miura Junnosuke , Ishizawa Kaya , Babazono Tetsuya
Published: May 2022

Aims/Introduction

To investigate the prevalence of depressive symptoms by the age of onset of type 1 diabetes, and its association with the condition of individuals with pediatric‐ and adolescent‐onset type 1 diabetes.

Materials and Methods

This single‐center cross‐sectional study enrolled Japanese participants with type 1 diabetes. All participants completed a questionnaire about their diabetes‐related condition and the Patient Health Questionnaire‐9, which was used to evaluate depression. Individuals with a Patient Health Questionnaire‐9 score of ≥10 points were defined as having moderate depressive symptoms.

Results

A total of 1,267 participants (mean age 40 years; mean duration of type 1 diabetes 21 years; 68% female; mean glycated hemoglobin 7.8%) were included and classified according to the age of onset of type 1 diabetes to identify the proportion of moderate depressive symptoms in each group: 21% (0–12 years), 18% (13–19 years) and 13% (20–40 years). The prevalence of moderate depressive symptoms was significantly higher among participants with pediatric‐onset type 1 diabetes (P < 0.05). Moderate depressive symptoms were associated with increased glycated hemoglobin, neuropathy and hypoglycemia unawareness.

Conclusions

Regular screening for depressive symptoms and hypoglycemia awareness is important. Healthcare professionals should provide appropriate psychosocial care for people with pediatric‐onset and adolescent‐onset type 1 diabetes from childhood through to adulthood.
Serious diabetic ketoacidosis induced by insulin allergy and anti‐insulin antibody in an individual with type 2 diabetes mellitus
Authors: Takahashi Kaio , Anno Takatoshi , Takenouchi Haruka , Iwamoto Hideyuki , Horiya Megumi , Kimura Yukiko , Kawasaki Fumiko , Kaku Kohei , Tomoda Koichi , Kaneto Hideaki
Published: May 2022

Diabetic ketoacidosis (DKA) is one of the most serious acute metabolic complications of diabetes mellitus, and is characterized by hyperglycemia, metabolic acidosis and increased total ketone body concentrations. The main mechanism of DKA is a lack of insulin in the body. It has been reported that some immunological response is associated with insulin therapy. Herein, we report a case of serious DKA, which was induced by insulin allergy and anti‐insulin antibody. This case clearly shows that DKA can be induced by insulin allergy and anti‐insulin antibodies in individuals with type 2 diabetes treated with insulin. Furthermore, we should know that as the required insulin dose might be very high under severe insulin resistance and serious DKA in such cases, we should increase the insulin dose appropriately while monitoring pH, base excess and other factors.
Association of ideal cardiovascular health metrics and incident type 2 diabetes mellitus among an urban population of Iran: One decade follow up in the Tehran Lipid and Glucose Study
Authors: Asgari Samaneh , Masrouri Soroush , Hosseinpour‐Niazi Somaye , Moslehi Nazanin , Azizi Fereidoun , Hadaegh Farzad
Published: May 2022

Aims/Introduction

To evaluate the association between ideal cardiovascular health metrics (ICVHM) and incident type 2 diabetes mellitus among Iranian men and women.

Materials and Methods

The study population included 7,488 Iranian adults aged ≥20 years (4,236 women) free from diabetes at baseline. The ICVHM was defined according to the American Heart Association's 2020 impact goals. The multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratios (HRs) for ICVHM both as continuous and categorical variables.

Results

Over the median of 9.1 years of follow‐up, we identified 922 new cases of type 2 diabetes mellitus (526 women). Body mass index <30 kg/m2, untreated systolic/diastolic blood pressure <120/80 mmHg in both sexes, and physical activity ≥1,500 MET min/week (only among men) were significantly associated with a lower risk of type 2 diabetes mellitus. Each additional unit in the ICVHM was associated with a 21 and 15% lower risk of type 2 diabetes mellitus in men and women, respectively (P‐values <0.05). Compared with participants having poor cardiovascular health, the HR for type 2 diabetes mellitus risk was 0.69 (95% confidence interval [CI] 0.56–0.85) and 0.35 (95% CI 0.21–0.59) for men with intermediate and ideal CVHM, respectively. The corresponding values for women were 0.79 (95% CI 0.65–0.97) and 0.30 (95% CI 0.15–0.60), respectively. In a subpopulation with nutritional data (n = 2,236), ideal and intermediate nutritional status was associated with 83 and 77% lower risk of type 2 diabetes mellitus only among women (P‐values <0.05).

Conclusion

We found a strong inverse association between having higher global ICVHM with incident type 2 diabetes mellitus; which is mainly attributable to normal blood pressure, normal body weight, and intensive physical activity (only for men).
PP2A interacts with KATANIN to promote microtubule organization and conical cell morphogenesis
Authors: Ren Huibo , Rao Jinqiu , Tang Min , Li Yaxing , Dang Xie , Lin Deshu
Published: May 2022

The organization of the microtubule cytoskeleton is critical for cell and organ morphogenesis. The evolutionarily conserved microtubule‐severing enzyme KATANIN plays critical roles in microtubule organization in the plant and animal kingdoms. We previously used conical cell of Arabidopsis thaliana petals as a model system to investigate cortical microtubule organization and cell morphogenesis and determined that KATANIN promotes the formation of circumferential cortical microtubule arrays in conical cells. Here, we demonstrate that the conserved protein phosphatase PP2A interacts with and dephosphorylates KATANIN to promote the formation of circumferential cortical microtubule arrays in conical cells. KATANIN undergoes cycles of phosphorylation and dephosphorylation. Using co‐immunoprecipitation coupled with mass spectrometry, we identified PP2A subunits as KATANIN‐interacting proteins. Further biochemical studies showed that PP2A interacts with and dephosphorylates KATANIN to stabilize its cellular abundance. Similar to the katanin mutant, mutants for genes encoding PP2A subunits showed disordered cortical microtubule arrays and defective conical cell shape. Taken together, these findings identify PP2A as a regulator of conical cell shape and suggest that PP2A mediates KATANIN phospho‐regulation during plant cell morphogenesis.
The acetylome of adult mouse sciatic nerve
Authors: Shen Mi , Chen Zixin , Ming Mengru , Cheng Zhenghui , Sun Junjie , Liang Qingyun , Shang Tongxin , Zhang Qi , Zhou Songlin , Ji Yuhua , Ding Fei
Published: May 2022

Lysine acetylation is a reversible post‐translational modification (PTM) involved in multiple physiological functions. Recent studies have demonstrated the involvement of protein acetylation in modulating the biology of Schwann cells (SCs) and regeneration of the peripheral nervous system (PNS). However, the mechanisms underlying these processes remain partially understood. Here, we characterized the acetylome of the mouse sciatic nerve (SN) and investigated the cellular distribution of acetylated proteins. We identified 483 acetylated proteins containing 1442 acetylation modification sites in the SN of adult C57BL/6 mice. Bioinformatics suggested that these acetylated SN proteins were mainly located in the myelin sheath, mitochondrial inner membrane, and cytoskeleton, and highlighted the significant differences between the mouse SN and brain acetylome. Manual annotation further indicated that most acetylated proteins (> 45%) were associated with mitochondria, energy metabolism, and cytoskeleton and cell adhesion. We verified three newly discovered acetylation‐modified proteins, including neurofilament light polypeptide (NEFL), neurofilament medium/high polypeptide (NFM/H), and periaxin (PRX). Immunofluorescence illustrated that the acetylated proteins, including acetylated alpha‐tubulin, were mainly co‐localized with S100‐positive SCs. Herein, we provided a comprehensive acetylome for the mouse SN and demonstrated that acetylated proteins in the SN were predominantly located in SCs. These results will extend our understanding and promote further study of the role and mechanism of protein acetylation in SC development and PNS regeneration.

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How parole boards judge remorse: Relational legal consciousness and the reproduction of carceral logic
Authors: Young Kathryne M. , Chimowitz Hannah
Published: May 2022

One in seven people in prison in the US is serving a life sentence, and most of these “lifers” will someday be eligible for discretionary parole. But little is known about a key aspect of parole decision-making: remorse assessments. Because remorse is a complex emotion that arises from past wrongdoing and unfolds over time, assessing the sincerity of another person's remorse is neither a simple task of lie detection, nor of determining emotional authenticity. Instead, remorse involves numerous elements, including the relationship between a person's past and present motivations, beliefs, and affective states. To understand how parole board members make sense of remorse, we draw on in-depth interviews with parole commissioners in California, the state with the largest proportion of parole-eligible lifers. We find that commissioners' remorse assessments hinge on their perceptions of lifers' relationships to law and carceral logic. In this way, relational legal consciousness—specifically, second-order legal consciousness—functions as a stand-in for the impossible task of knowing another person's heart or mind. We distinguish relational from second-order legal consciousness and argue that understanding how they operate at parole hearings reveals the larger import of relational legal consciousness as a mechanism via which existing power relations are produced and reproduced, bridging the legal consciousness and law and emotion literatures.
Phosphatidylinositol 4‐phosphate: a key determinant of plasma membrane identity and function in plants
Authors: Marković Vedrana , Jaillais Yvon
Published: May 2022

Phosphatidylinositol 4‐phosphate (PI4P) is an anionic phospholipid which has been described as a master regulator of the Golgi apparatus in eukaryotic cells. However, recent evidence suggests that PI4P mainly accumulates at the plasma membrane in all plant cells analyzed so far. In addition, many functions that are typically attributed to phosphatidylinositol 4,5‐bisphosphate (PI(4,5)P2) in animal and yeast cells are also supported by PI4P in plants. For example, PI4P is the key anionic lipid that powers the strong electrostatic properties of the plasma membrane. Phosphatidylinositol 4‐phosphate is also required for the establishment of stable membrane contacts between the endoplasmic reticulum and the plasma membrane, for exocytosis and to support signaling pathways. Thus, we propose that PI4P has a prominent role in specifying the identity of the plasma membrane and in supporting some of its key functions and should be considered a hallmark lipid of this compartment.
Multispecies forest plantations outyield monocultures across a broad range of conditions
Authors: Feng Yuhao , Schmid Bernhard , Loreau Michel , Forrester David I. , Fei Songlin , Zhu Jianxiao , Tang Zhiyao , Zhu Jiangling , Hong Pubin , Ji Chengjun , Shi Yue , Su Haojie , Xiong Xinyu , Xiao Jian , Wang Shaopeng , Fang Jingyun
Published: May 2022

Multispecies tree planting has long been applied in forestry and landscape restoration in the hope of providing better timber production and ecosystem services; however, a systematic assessment of its effectiveness is lacking. We compiled a global dataset of matched single-species and multispecies plantations to evaluate the impact of multispecies planting on stand growth. Average tree height, diameter at breast height, and aboveground biomass were 5.4, 6.8, and 25.5% higher, respectively, in multispecies stands compared with single-species stands. These positive effects were mainly the result of interspecific complementarity and were modulated by differences in leaf morphology and leaf life span, stand age, planting density, and temperature. Our results have implications for designing afforestation and reforestation strategies and bridging experimental studies of biodiversity–ecosystem functioning relationships with real-world practices.
Epistatic drift causes gradual decay of predictability in protein evolution
Authors: Park Yeonwoo , Metzger Brian P. H. , Thornton Joseph W.
Published: May 2022

Epistatic interactions can make the outcomes of evolution unpredictable, but no comprehensive data are available on the extent and temporal dynamics of changes in the effects of mutations as protein sequences evolve. Here, we use phylogenetic deep mutational scanning to measure the functional effect of every possible amino acid mutation in a series of ancestral and extant steroid receptor DNA binding domains. Across 700 million years of evolution, epistatic interactions caused the effects of most mutations to become decorrelated from their initial effects and their windows of evolutionary accessibility to open and close transiently. Most effects changed gradually and without bias at rates that were largely constant across time, indicating a neutral process caused by many weak epistatic interactions. Our findings show that protein sequences drift inexorably into contingency and unpredictability, but that the process is statistically predictable, given sufficient phylogenetic and experimental data.
Fossil imprints from oceans of the past
Authors: Henderiks Jorijntje
Published: May 2022

Marine phytoplankton show notable resilience during extreme ocean states
Mitochondrial complex complexification
Authors: Huynen Martijn A. , Elurbe Dei M.
Published: May 2022

Variation in complex composition provides clues about the function of individual subunits
T cell immune responses deciphered
Authors: Nourmohammad Armita
Published: May 2022

A machine-learning approach reveals antigen encoding that predicts T cell responses
Synergistic Inactivation of African Swine Fever Virus by a Highly Complexed Iodine Combined with Compound Organic Acids
Authors: Qi Mengnan , Pan Li , Gao Ying , Li Miao , Wang Yanjin , Li Lian-Feng , Ji Chen , Sun Yuan , Qiu Hua-Ji
Published: May 2022

African swine fever (ASF) is a highly contagious disease of swine with high morbidity and mortality caused by African swine fever virus (ASFV). Due to the lack of commercial vaccines and treatment available for ASF, effective disinfectants and the proper use of them are essential to inactivate ASFV.
Nonsynonymous Mutations in
fepR
Are Associated with Adaptation of Listeria monocytogenes and Other
Listeria
spp. to Low Concentrations of Benzalkonium Chloride but Do Not Increase Survival of L. monocytogenes and Other
Listeria
spp. after Exposure to Benzalkonium Chloride Concentrations Recommended for Use in Food Processing Environments
Authors: Bolten Samantha , Harrand Anna Sophia , Skeens Jordan , Wiedmann Martin
Published: May 2022

Listeria monocytogenes
tolerance to quaternary ammonium compounds has been raised as a concern with regard to
L. monocytogenes
persistence in food processing environments, including in fresh produce packing and processing environments. Persistence of
L. monocytogenes
can increase the risk of product contamination, food recalls, and foodborne illness outbreaks.
Life Stories: Tools for Knowledge Integration
Authors: Marintcheva Boriana
Published: May 2022

Life is very complex. As our understanding of living matter continues to deepen, naturally biology teaching is becoming increasingly detail oriented.
Disruption of Toxoplasma gondii-Induced Host Cell DNA Replication Is Dependent on Contact Inhibition and Host Cell Type
Authors: Pierre-Louis Edwin , Etheridge Menna G. , de Paula Baptista Rodrigo , Khan Asis , Chasen Nathan M. , Etheridge Ronald D.
Published: May 2022

Toxoplasma gondii
chronically infects approximately one-third of the global population and can produce severe pathology in immunologically immature or compromised individuals. During infection, this parasite releases numerous host-targeted effector proteins that can dramatically alter the expression of a variety of host genes.
Supplemental Material: Geophysical extent of the Wyoming Province, western USA: Insights into ancient subduction and craton stability
Authors: Bedrosian Paul A. , Frost Carol D.
Published: May 2022

(1) A published compilation of U-Pb zircon, monazite, titanite and baddeleyite age determinations of igneous and metamorphic rocks from the WP and adjacent areas. This compilation is provided as both an Excel spreadsheet (B36417_SuppMat1.xls) and shapefile (B36417_SuppMat1.zip). (2) A compilation of published magnetotelluric studies over known suture zones (B36417_SuppMat2.xls). (3) A report and spreadsheet (B36417_SuppMat3.xls) documenting a newly reported U-Pb zircon age on gneiss sample 04SP-QF from the Wind River Range, Wyoming. (4) Figures summarizing the data fit of the final 3-D resistivity model. 
Novel treatments in B cell non-Hodgkin’s lymphomas
Authors: Sawalha Yazeed , Maddocks Kami
Published: May 2022

The improved understanding of lymphoma biology and recent advances in the field of cancer immunology have paved the way for the development of many effective small molecule inhibitors and immunotherapies in B cell non-Hodgkin’s lymphomas. This article reviews novel treatments that have been approved recently by the US Food and Drug Administration and are now routinely used in clinical practice. It discusses their mechanisms of action, efficacy and safety, current therapeutic roles, and future directions in the treatment paradigm of different types of B cell non-Hodgkin’s lymphoma. It also reviews other exciting novel treatments that are not yet approved but have unique mechanisms of action and have shown encouraging early results.
Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study
Authors: Katsoularis Ioannis , Fonseca-Rodríguez Osvaldo , Farrington Paddy , Jerndal Hanna , Lundevaller Erling Häggström , Sund Malin , Lindmark Krister , Fors Connolly Anne-Marie
Published: May 2022

Objective

To quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19.

Design

Self-controlled case series and matched cohort study.

Setting

National registries in Sweden.

Participants

1 057 174 people who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021 in Sweden, matched on age, sex, and county of residence to 4 076 342 control participants.

Main outcomes measures

Self-controlled case series and conditional Poisson regression were used to determine the incidence rate ratio and risk ratio with corresponding 95% confidence intervals for a first deep vein thrombosis, pulmonary embolism, or bleeding event. In the self-controlled case series, the incidence rate ratios for first time outcomes after covid-19 were determined using set time intervals and the spline model. The risk ratios for first time and all events were determined during days 1-30 after covid-19 or index date using the matched cohort study, and adjusting for potential confounders (comorbidities, cancer, surgery, long term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event).

Results

Compared with the control period, incidence rate ratios were significantly increased 70 days after covid-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding. In particular, incidence rate ratios for a first pulmonary embolism were 36.17 (95% confidence interval 31.55 to 41.47) during the first week after covid-19 and 46.40 (40.61 to 53.02) during the second week. Incidence rate ratios during days 1-30 after covid-19 were 5.90 (5.12 to 6.80) for deep vein thrombosis, 31.59 (27.99 to 35.63) for pulmonary embolism, and 2.48 (2.30 to 2.68) for bleeding. Similarly, the risk ratios during days 1-30 after covid-19 were 4.98 (4.96 to 5.01) for deep vein thrombosis, 33.05 (32.8 to 33.3) for pulmonary embolism, and 1.88 (1.71 to 2.07) for bleeding, after adjusting for the effect of potential confounders. The rate ratios were highest in patients with critical covid-19 and highest during the first pandemic wave in Sweden compared with the second and third waves. In the same period, the absolute risk among patients with covid-19 was 0.039% (401 events) for deep vein thrombosis, 0.17% (1761 events) for pulmonary embolism, and 0.101% (1002 events) for bleeding.

Conclusions

The findings of this study suggest that covid-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after covid-19.
How conflicts of interest hinder effective regulation of healthcare: an analysis of antimicrobial use regulation in Cambodia, Indonesia and Pakistan
Authors: Khan Mishal , Rahman-Shepherd Afifah , Bory Sothavireak , Chhorn Sophea , Durrance-Bagale Anna , Hasan Rumina , Heng Sotheara , Phou Socheata , Prien Chanra , Probandari Ari , Saphonn Vonthanak , Suy Sovanthida , Wiseman Virginia , Wulandari Luh Putu Lila , Hanefeld Johanna
Published: May 2022

Background

There has been insufficient attention to a fundamental force shaping healthcare policies—conflicts of interest (COI). We investigated COI, which results in the professional judgement of a policymaker or healthcare provider being compromised by a secondary interest, in relation to antimicrobial use, thereby illuminating challenges to the regulation of medicines use more broadly. Our objectives were to characterise connections between three groups—policymakers, healthcare providers and pharmaceutical companies—that can create COI, and elucidate the impacts of COI on stages of the policy process.

Methods

Using an interpretive approach, we systematically analysed qualitative data from 136 in-depth interviews and five focus group discussions in three Asian countries with dominant private healthcare sectors: Cambodia, Indonesia and Pakistan.

Findings

We characterised four types of connections that were pervasive between the three groups: financial, political, social and familial. These connections created strong COI that could impact all stages of the policy process by: preventing issues related to medicines sales from featuring prominently on the agenda; influencing policy formulation towards softer regulatory measures; determining resource availability for, and opposition to, policy implementation; and shaping how accurately the success of contested policies is reported.

Interpretation

Our multicountry study fills a gap in empirical evidence on how COI can impede effective policies to improve the quality of healthcare. It shows that COI can be pervasive, rather than sporadic, in influencing regulation of medicine use, and highlights that, in addition to financial connections, other types of connections should be examined as important drivers of COI.
Medical negligence claims and the health and life satisfaction of Australian doctors: a prospective cohort analysis of the MABEL survey
Authors: Bradfield Owen M , Bismark Marie , Scott Anthony , Spittal Matthew
Published: May 2022

Objective

To assess the association between medical negligence claims and doctors’ self-rated health and life satisfaction.

Design

Prospective cohort study.

Participants

Registered doctors practising in Australia who participated in waves 4 to 11 of the Medicine in Australia: Balancing Employment and Life (MABEL) longitudinal survey between 2011 and 2018.

Primary and secondary outcome measures

Self-rated health and self-rated life satisfaction.

Results

Of the 15 105 doctors in the study, 885 reported being named in a medical negligence claim. Fixed-effects linear regression analysis showed that both self-rated health and self-rated life satisfaction declined for all doctors over the course of the MABEL survey, with no association between wave and being sued. However, being sued was not associated with any additional declines in self-rated health (coef.=−0.02, 95% CI −0.06 to 0.02, p=0.39) or self-rated life satisfaction (coef.=−0.01, 95% CI −0.08 to 0.07, p=0.91) after controlling for a range of job factors. Instead, we found that working conditions and job satisfaction were the strongest predictors of self-rated health and self-rated life satisfaction in sued doctors. In analyses restricted to doctors who were sued, we observed no changes in self-rated health (p=0.99) or self-rated life satisfaction (p=0.59) in the years immediately following a claim.

Conclusions

In contrast to prior overseas cross-sectional survey studies, we show that medical negligence claims do not adversely affect the well-being of doctors in Australia when adjusting for time trends and previously established covariates. This may be because: (1) prior studies failed to adequately address issues of causation and confounding; or (2) legal processes governing medical negligence claims in Australia cause less distress compared with those in other jurisdictions. Our findings suggest that the interaction between medical negligence claims and poor doctors’ health is more complex than revealed through previous studies.
Pandemic impact on patients with advanced non-COVID-19 illness and their family carers receiving specialised palliative home care: a qualitative study
Authors: Nyblom Stina , Benkel Inger , Carling Linnéa , Löfdahl Elisabet , Molander Ulla , Öhlén Joakim
Published: May 2022

Objectives

To investigate the experiential impact of the COVID-19 pandemic on patients with non-COVID, life-threatening disease and their family carers.

Design

An interpretative qualitative design informed by phenomenological hermeneutics and based on data from in-depth interviews, performed between June and September 2020.

Setting

Patients receiving specialised palliative home care and their family carers living in Sweden.

Participants

22 patients (male/female 11/11) and 17 carers (male/female 5/12) aged 50 years and older. All the patients received specialised palliative home care and most were diagnosed with cancer. Inclusion criteria: aged 18 years or older, diagnosed with an incurable life-threatening, non-COVID disease, sufficient strength to participate and capacity to provide informed consent. Participants were selected through a combination of convenient and consecutive sampling.

Results

The significance of the pandemic for both patients and carers showed a continuum from being minimally affected in comparison to the severe underlying disease to living in isolation with constant fear of becoming infected and falling ill with COVID-19, which some likened to torture.

The imposed restrictions on social contact due to the pandemic were particularly palpable for this group of people with a non-COVID-19, life-limiting condition, as it was said to steal valuable moments of time that had already been measured.

Most patients and carers found access to specialised palliative home care was maintained despite the pandemic. This care was of paramount importance for their sense of security and was often their sole visiting social contact.

Conclusions

In the pandemic situation, highly accessible support from healthcare and social care at home is particularly important to create security for both patients and carers. Thus, to provide appropriate support, it is important for healthcare and social care personnel to be aware of the great diversity of reactions patients in palliative care and their carers may have to a pandemic threat.
Prior AICAR induces elevated glucose uptake concomitant with greater γ3-AMPK activation and reduced membrane cholesterol in skeletal muscle from 26-month-old rats
Authors: Wang Haiyan , Zheng Amy , Arias Edward B. , Cartee Gregory D.
Published: May 2022

Attenuated skeletal muscle glucose uptake (GU) has been observed with advancing age. It is important to elucidate the mechanisms linked to interventions that oppose this detrimental outcome. Earlier research using young rodents and (or) cultured myocytes reported that treatment with 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR; an AMP-activated protein kinase (AMPK) activator) can increase γ3-AMPK activity and reduce membrane cholesterol content, each of which has been proposed to elevate GU. However, the effect of AICAR treatment on γ3-AMPK activity and membrane cholesterol in skeletal muscle of aged animals has not been reported. Our purpose was to evaluate the effects of AICAR treatment on these potential mechanisms for enhanced glucose uptake in the skeletal muscle of aged animals. Epitrochlearis muscles from 26–27-month-old male rats were isolated and incubated ± AICAR, followed by 3 h incubation without AICAR, and then incubation with 3- O-methyl-[3 H] glucose (to assess GU ± insulin). Muscles were also analyzed for γ3-AMPK activity and membrane cholesterol content. Prior AICAR treatment led to increased γ3-AMPK activity, reduced membrane cholesterol content, and enhanced glucose uptake in skeletal muscle from aged rats. These observations revealed that two potential mechanisms for greater GU previously observed in younger animals and (or) cell models are also potentially relevant for enhanced GU by muscles from older animals.
MedLatinEpi
and
MedLatinLit
: Two Datasets for the Computational Authorship Analysis of Medieval Latin Texts
Authors: Corbara Silvia , Moreo Alejandro , Sebastiani Fabrizio , Tavoni Mirko
Published: May 2022

We present and make available
MedLatinEpi
and
MedLatinLit
, two datasets of medieval Latin texts to be used in research on computational authorship analysis.
MedLatinEpi
and
MedLatinLit
consist of 294 and 30 curated texts, respectively, labelled by author;
MedLatinEpi
texts are of epistolary nature, while
MedLatinLit
texts consist of literary comments and treatises about various subjects. As such, these two datasets lend themselves to supporting research in authorship analysis tasks, such as authorship attribution, authorship verification, or same-author verification. Along with the datasets, we provide experimental results, obtained on these datasets, for the authorship verification task, i.e., the task of predicting whether a text of unknown authorship was written by a candidate author. We also make available the source code of the authorship verification system we have used, thus allowing our experiments to be reproduced, and to be used as baselines, by other researchers. We also describe the application of the above authorship verification system, using these datasets as training data, for investigating the authorship of two medieval epistles whose authorship has been disputed by scholars.
Inclusive Improvisation: Exploring the Line between Listening and Playing Music
Authors: Ilsar Alon , Kenning Gail , Trolland Sam , Frame Ciaran
Published: May 2022

The field of Accessible Digital Musical Instruments (ADMIs) is growing rapidly, with instrument designers recognising that adaptations to existing Digital Musical Instruments (DMIs) can foster inclusive music making. ADMIs offer opportunities to engage with a wider range of sounds than acoustic instruments. Furthermore, gestural ADMIs free the music maker from relying on screen, keyboard, and mouse-based interfaces for engaging with these sounds. This brings greater opportunities for exploration, improvisation, empowerment, and flow through music making for people with disability and the communities of practice they are part of. This article argues that developing ADMIs from existing DMIs can speed up the process and allow for more immediate access for those with diverse needs. It presents three case studies of a gestural DMI, originally designed by the first author for his own creative practice, played by people with disability in diverse contexts. The article shows that system-based considerations that enabled an expert percussionist to achieve virtuoso performances with the instrument required minimal hardware and software changes to facilitate greater inclusivity. Understanding the needs of players and customising the system-based movement to sound mappings was of far greater importance in making the instrument accessible.
Physiological Functions of Intracellular Protein Degradation
Authors: McShane Erik , Selbach Matthias
Published: May 2022

While cellular proteins were initially thought to be stable, research over the last decades has firmly established that intracellular protein degradation is an active and highly regulated process: Lysosomal, proteasomal, and mitochondrial degradation systems were identified and found to be involved in a staggering number of biological functions. Here, we provide a global overview of the diverse roles of cellular protein degradation using seven categories: homeostasis, regulation, quality control, stoichiometry control, proteome remodeling, immune surveillance, and baseline turnover. Using selected examples, we outline how proteins are degraded and why this is functionally relevant.
Epigenetic Reprogramming in Host-Parasite Coevolution: TheToxoplasmaParadigm
Authors: Hakimi Mohamed-Ali
Published: May 2022

Like many intracellular pathogens, the protozoan parasite Toxoplasma gondii has evolved sophisticated mechanisms to promote its transmission and persistence in a variety of hosts by injecting effector proteins that manipulate many processes in the cells it invades. Specifically, the parasite diverts host epigenetic modulators and modifiers from their native functions to rewire host gene expression to counteract the innate immune response and to limit its strength. The arms race between the parasite and its hosts has led to accelerated adaptive evolution of effector proteins and the unconventional secretion routes they use. This review provides an up-to-date overview of how T. gondii effectors, through the evolution of intrinsically disordered domains, the formation of supramolecular complexes, and the use of molecular mimicry, target host transcription factors that act as coordinating nodes, as well as chromatin-modifying enzymes, to control the fate of infected cells and ultimately the outcome of infection.
The Lard Works in Mysterious Ways: Ceramides in Nutrition-Linked Chronic Disease
Authors: Nicholson Rebekah J. , Norris Marie K. , Poss Annelise M. , Holland William L. , Summers Scott A.
Published: May 2022

Diet influences onset, progression, and severity of several chronic diseases, including heart failure, diabetes, steatohepatitis, and a subset of cancers. The prevalence and clinical burden of these obesity-linked diseases has risen over the past two decades. These metabolic disorders are driven by ectopic lipid deposition in tissues not suited for fat storage, leading to lipotoxic disruption of cell function and survival. Sphingolipids such as ceramides are among the most deleterious and bioactive metabolites that accrue, as they participate in selective insulin resistance, dyslipidemia, oxidative stress and apoptosis. This review discusses our current understanding of biochemical pathways controlling ceramide synthesis, production and action; influences of diet on ceramide levels; application of circulating ceramides as clinical biomarkers of metabolic disease; and molecular mechanisms linking ceramides to altered metabolism and survival of cells. Development of nutritional or pharmacological strategies to lower ceramides could have therapeutic value in a wide range of prevalent diseases.
Exploring Soybean Resistance to Soybean Cyst Nematode
Authors: Bent Andrew F.
Published: May 2022

Resistance to the soybean cyst nematode (SCN) is a topic incorporating multiple mechanisms and multiple types of science. It is also a topic of substantial agricultural importance, as SCN is estimated to cause more yield damage than any other pathogen of soybean, one of the world's main food crops. Both soybean and SCN have experienced jumps in experimental tractability in the past decade, and significant advances have been made. The rhg1-b locus, deployed on millions of farm acres, has been durable and will remain important, but local SCN populations are gradually evolving to overcome rhg1-b. Multiple other SCN resistance quantitative trait loci (QTL) of proven value are now in play with soybean breeders. QTL causal gene discovery and mechanistic insights into SCN resistance are contributing to both basic and applied disciplines. Additional understanding of SCN and other cyst nematodes will also grow in importance and lead to novel disease control strategies.
Facilitating Reforestation Through the Plant Microbiome: Perspectives from the Phyllosphere
Authors: Busby Posy E. , Newcombe George , Neat Abigail S. , Averill Colin
Published: May 2022

Tree planting and natural regeneration contribute to the ongoing effort to restore Earth's forests. Our review addresses how the plant microbiome can enhance the survival of planted and naturally regenerating seedlings and serve in long-term forest carbon capture and the conservation of biodiversity. We focus on fungal leaf endophytes, ubiquitous defensive symbionts that protect against pathogens. We first show that fungal and oomycetous pathogen richness varies greatly for tree species native to the United States ( n = 0–876 known pathogens per US tree species), with nearly half of tree species either without pathogens in these major groups or with unknown pathogens. Endophytes are insurance against the poorly known and changing threat of tree pathogens. Next, we review studies of plant phyllosphere feedback, but knowledge gaps prevent us from evaluating whether adding conspecific leaf litter to planted seedlings promotes defensive symbiosis, analogous to adding soil to promote positive feedback. Finally, we discuss research priorities for integrating the plant microbiome into efforts to expand Earth's forests.