bluuebunny/crossref_metadata_2025 huggingface dataset:
Perilipin-1 autoantibodies linked to idiopathic lipodystrophy in the setting of two distinct breaks in immune tolerance
Authors: Mandel-Brehm Caleigh , Vazquez Sara E. , Liverman Christopher , Cheng Mickie , Quandt Zoe , Kung Andrew F. , Miao Brenda , Disse Emmanuel , Cugnet-Anceau Christine , Dalle Stéphane , Orlova Elizaveta , Frolova Elena , Oftedal Bergithe E. , Lionakis Michail S. , Husebye Eystein S. , DeRisi Joseph L. , Anderson Mark S.
Published: September 2021

Background

Acquired lipodystrophy is often characterized as an idiopathic subtype of lipodystrophy. Despite suspicion of an immune-mediated pathology, biomarkers such as autoantibodies are generally lacking.

Methods

Here, we used an unbiased proteome-wide screening approach to identify autoantibodies to the adipocyte specific lipid droplet protein Perilipin-1 in a murine model of Autoimmune Polyendocrine Syndrome 1 (APS1). We then tested for PLIN1 autoantibodies in human subjects with lipodystrophy with two independent severe breaks in immune tolerance (including APS1) along with controls using a specific Radioligand Binding Assay and indirect immunofluorescence on fat tissue.

Results

We identified autoantibodies to the lipid-droplet protein Perilipin-1 (PLIN1) in two human case reports including the first reported case of human APS1 with acquired lipodystrophy. Further, we extend PLIN1 autoantibodies to a second non-APS1 patient who acquired lipodystrophy as an immune-related adverse event following cancer immunotherapy.

Conclusion

These data suggest that PLIN1 autoantibodies may represent a unifying marker of autoimmune lipodystrophy.
N-acetyl-L-leucine improves symptoms and functioning in GM2 Gangliosidosis (Tay-Sachs & Sandhoff)
Authors: Martakis Kyriakos , Claassen Jens , Gascon-Bayarri Jordi , Goldschagg Nicolina , Hahn Andreas , Hassan Anhar , Hennig Anita , Jones Simon A. , Lau Heather , Perlman Susan , Sharma Reena , Schneider Susanne A. , Bremova-Ertl Tatiana
Published: September 2021

Background and Objective

GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases) are rare, inherited neurodegenerative disorders with no available symptomatic or disease modifying treatments. This clinical trial aimed to investigate the safety and efficacy of N-acetyl-L-leucine (NALL) on symptoms of pediatric (≥ 6 years) and adult patients with GM2 gangliosidosis.

Methods

\We conducted an 8-center, multi-national, open-label, rater-blinded Phase IIb study (IB1001-201). Patients with a genetically confirmed diagnosis of GM2 gangliosidosis were assessed during a baseline period, a 6-week treatment period (orally administered NALL 4 g/day in patients ≥13 years, weight-tiered doses for patients 6-12 years), and a 6-week post-treatment washout period. The primary Clinical Impression of Change in Severity (CI-CS) endpoint (based on a 7-point Likert scale) was assessed by blinded, centralized raters who compared randomized video pairs of each patient performing a pre-defined primary anchor test (8-Meter Walk Test or 9-Hole Peg Test) during each study periods. Secondary outcomes included cerebellar rating scales (namely Scale for the Assessment and Rating of Ataxia), clinical global impression, and quality of life assessments.

Results

30 patients aged 6 to 55 years with a confirmed diagnosis of GM2 gangliosidosis (Tay-Sachs or Sandhoff’s disease) were enrolled. 29 patients were included in the primary modified intention-to-treat analysis. NALL met the CI-CS primary endpoint (mean difference 0.71, SD=2.09, 90% CI 0.00, 1.50, p=0.044), as well as secondary endpoints. No treatment-related serious adverse events occurred.

Conclusions

This study showed NALL led to a statistically significant improvement in symptoms, functioning, and quality of life in patients with GM2 gangliosidosis. It is a safe, well-tolerated, easily administered oral therapy, therefore offering a favorable risk/benefit profile for this serious, debilitating disorder. NALL is a new therapeutic option for the treatment of this rare disease that has no other approved therapies worldwide.

Classification of Evidence

This study provides Class IV evidence NALL is safe, well-tolerated, and improves neurological symptoms and quality of life in patients with GM2 gangliosidosis.

Trial Registration Information

The trial is registered with ClinicalTrials.gov (NCT03759665; registered 30-Nov-2018), EudraCT (2018-004406-25), and DRKS (DRKS00017539). The first patient was enrolled 07-June-2019.
Quality control and removal of technical variation of NMR metabolic biomarker data in ∼120,000 UK Biobank participants
Authors: Ritchie Scott C. , Surendran Praveen , Karthikeyan Savita , Lambert Samuel A. , Bolton Thomas , Pennells Lisa , Danesh John , Di Angelantonio Emanuele , Butterworth Adam S. , Inouye Michael
Published: September 2021

Metabolic biomarker data quantified by nuclear magnetic resonance (NMR) spectroscopy has recently become available in UK Biobank. Here, we describe procedures for quality control and removal of technical variation for this biomarker data, comprising 249 circulating metabolites, lipids, and lipoprotein sub-fractions on approximately 121,000 participants. We identify and characterise technical and biological factors associated with individual biomarkers and find that linear effects on individual biomarkers can combine in a non-linear fashion for 61 composite biomarkers and 81 biomarker ratios. We create an R package, ukbnmr, for extracting and normalising the metabolic biomarker data, then use ukbnmr to remove unwanted variation from the UK Biobank data. We make available code for re-deriving the 61 composite biomarkers and 81 ratios, and for further derivation of 76 additional biomarker ratios of potential biological significance. Finally, we demonstrate that removal of technical variation leads to increased signal for genetic and epidemiological studies of the NMR metabolic biomarkers in UK Biobank.
Systems Leadership: how Chief Executives manage tension between organisation and system pressures
Authors: Gordon Ben , Thomas Matthew Gwynfryn , Aufegger Lisa , Darzi Ara , Bicknell Colin
Published: September 2021

Aim

System leadership is the requirement for a leader of a single organisation to operate on behalf of a wider system, rather than their individual organisation. It is not clear to what extent the current policy landscape supports leaders in managing misalignment between the needs of their organisation and the wider system, as many national structures still emphasise a focus on individual organisations. This study aims to understand how Chief Executives implement system leadership in practice when faced with decisions that benefit the system to the detriment of their own trust.

Methodology

Semi-structured interviews were conducted with ten Chief Executives from a range of trust types to understand their perceptions and decision-making process in practice. Semantic thematic analysis was used to draw out themes in relation to how Chief Executives approach decisions which weigh up the system and organisation.

Results

Themes raised by interviewees included both advantages (such as support in managing demand) and disadvantages (such as increased bureaucracy) of system leadership and practical considerations in operationalisation (such as the importance of interpersonal relationships). Interviewees endorsed system leadership in principle, but did not feel that the organisational incentives as currently structured support the implementation of system leadership in practice. This was not seen as a major challenge or impediment to effective leadership.

Conclusion

As a specific policy area, a direct focus on systems leadership is not necessarily helpful. Chief Executives should be supported to make decisions in a complex environment, without a specific focus on healthcare systems as a unit of operation.
Biomimetic Vasculatures by 3D-Printed Porous Molds
Authors: Ching Terry , Vasudevan Jyothsna , Chang Shu-Yung , Tan Hsih Yin , Lim Chwee Teck , Fernandez Javier. G. , Ng Jun Jie , Toh Yi-Chin , Hashimoto Michinao
Published: September 2021

Anatomically and biologically relevant vascular models are critical to progress our understanding of cardiovascular diseases (CVDs) that can lead to effective therapies. Despite advances in 3D bioprinting, recapitulating complex architectures (i.e., freestanding, branching, multilayered, perfusable) of a cell-laden vascular construct remains technically challenging, and the development of new techniques that can recapitulate both anatomical and biological features of blood vessels is of paramount importance. In this work, we introduce a unique, microfluidics-enabled molding technique that allows us to fabricate anatomically-relevant, cell-laden hydrogel vascular models. Our approach employed 3D-printed porous molds of poly(ethylene glycol) diacrylate (PEGDA) as templates to cast alginate-containing bioinks. Due to the porous and aqueous nature of the PEGDA mold, the calcium ion (Ca2+) was diffusively released to crosslink the bioinks to create hollow structures. Applying this technique, multiscale, multilayered vascular constructs that were freestanding and perfusable were readily fabricated using cell-compatible bioinks (i.e., alginate and gelatin methacryloyl (GelMA)). The bioinks were also readily customizable to either improve the compatibility with specific vascular cells or tune the mechanical modulus to mimic native blood vessels. Importantly, we successfully integrated smooth muscle cells and endothelial cells in a biomimetic organization within our vessel constructs and demonstrated a significant increase in monocyte adhesion upon stimulation with an inflammatory cytokine, tumor necrosis factor-alpha (TNF-α). We also demonstrated that the fabricated vessels were amenable for testing percutaneous coronary interventions (i.e., drug-eluting balloons and stents) under physiologically-relevant mechanical states, such as vessel stretching and bending. Overall, we introduce a versatile fabrication technique with multi-faceted possibilities of generating biomimetic vascular models that can benefit future research in mechanistic understanding of CVD progression and the development of therapeutic interventions.
Characterizing SERCA function in murine skeletal muscles after 35-37 days of spaceflight
Authors: Braun Jessica L. , Geromella Mia S. , Hamstra Sophie I. , Messner Holt N. , Fajardo Val A.
Published: September 2021

It is well established that microgravity exposure causes significant muscle weakness and atrophy via muscle unloading. On Earth, muscle unloading leads to a disproportionate loss in muscle force and size with the loss in muscle force occurring at a faster rate. Though the exact mechanisms are unknown, a role for Ca2+dysregulation has been suggested. The sarco(endo)plasmic reticulum Ca2+ATPase (SERCA) pump actively brings cytosolic Ca2+into the SR, eliciting muscle relaxation and maintaining low intracellular Ca2+([Ca2+]i). SERCA dysfunction contributes to elevations in [Ca2+]i, leading to cellular damage and thus may contribute to the muscle weakness and atrophy observed with spaceflight. Here, we investigated SERCA function, SERCA regulatory protein content (sarcolipin, phospholamban, and neuronatin), and reactive oxygen/nitrogen species (RONS) protein adduction in murine skeletal muscle after 35-37 days of spaceflight. In male and female soleus muscles, spaceflight led to drastic impairments in Ca2+uptake despite significant increases in SERCA1a protein content. We attribute this impairment to an increase in RONS production and elevated total protein tyrosine (T) nitration and cysteine (S) nitrosylation. Contrarily, in the tibialis anterior (TA) we observed an enhancement in Ca2+uptake, which we attribute to a shift towards a faster muscle fiber type (i.e., increased myosin heavy chain IIb and SERCA1a) without elevated total protein T-nitration and S-nitrosylation. Thus, spaceflight affects SERCA function differently between the soleus and TA. As the soleus is severely affected by spaceflight, future studies should determine whether improving SERCA function in this muscle can mitigate muscle atrophy and weakness.
Tetraammonium μ-ethylenediaminetetraacetato-1κ3
O,N,O′:2κ3
O′′,N′,O′′′-bis[trioxidotungstate(VI)] tetrahydrate
Authors: Yaffa Lamine , Pouye Sérigne Fallou , Ndoye Daouda , Diallo Waly , Diop Mayoro , Sidibe Mamadou , Diop Cheikh Abdoul Khadir
Published: September 2021

The title compound, (NH4)4[W2(C10H12N2O8)O6]·4H2O, was obtained from a mixture of tungstic acid, ammonia and ethylenediaminetetraacetic acid (H4edta) in a 2:4:1 ratio. The anion of the complex contains two WO3 units and one bridging edta4− ligand. Each central metal atom is tridentately coordinated by nitrogen and two carboxylate groups of the edta4− ligand, together with the three oxido ligands, producing a distorted octahedral coordination environment around each tungsten atom. The center of the carbon–carbon bond of the ethylene bridge represents a crystallographic inversion center. The crystal structure consists of a three-dimensional supramolecular framework built up by the dinuclear cations, the ammonium counter-ions and the solvent water molecules via hydrogen bonds of the N—H...O and O—H...O type.
Contribution of PRME in education, research, and outreach in Brazilian higher education institutions
Authors: Avelar Aline Bento Ambrósio , Silva-Oliveira Keilla Dayane da , Farina Milton Carlos , Pereira Raquel da Silva
Published: September 2021

Purpose

This paper aims to assess the contribution of the UN’s Principles for Responsible Management Education (PRME) in higher education, covering education, research and outreach in Brazilian higher education institutions (HEIs) after becoming signatories.

Design/methodology/approach

Teachers representing Brazilian HEI signatories to the PRME were interviewed. The IRAMUTEQ software was used for content analysis, descending hierarchical classification and similarity tree, allowing to quantify the quality variables originating from the professors’ beliefs and opinions.

Findings

The PRME helps Brazilian HEIs to review or create disciplines related to responsible management education and adopt transdisciplinarity for sustainability. The signatories’ PRME-influenced research is interdisciplinary, focusing on the UN’s Sustainable Development Goals (SDGs). Social responsibility is promoted through local-community projects, while partnerships, initiatives and innovative pedagogies from foreign-signatory HEIs provide international experiences for teachers and students. However, within one initiative, which had 170 signatories in 2008 and over 800 in 2020, indicators should be formulated to analyze and enhance HEIs’ sustainability profile. The PRME contributes to educating young people and adults in Brazil via education, research or outreach; however, this contribution needs to be assessed.

Originality/value

Prior studies have not collected data through interviews to consider professors’ perspectives on the PRME’s contribution to signatory HEIs in Brazil. This study interviewed professors involved with the PRME to broaden their understanding beyond bibliometrics and assess the alignment of the PRME and UN SDGs.
Green strategies and relationship maintenance: a network evolution perspective
Authors: Han Pengfei , Wang Haifeng , Fan Peihua
Published: September 2021

Purpose

Along with the important impact of green strategies on firm survival and performance improvement, its dark side likewise requires attention. By integrating network evolution theory with the literature on green supply chain management, this study proposes a theoretical framework consisting of green strategies, network conduct (cooperation length), network structure (structural holes) and relationship maintenance. The purpose of this study is to indicate how green strategies can affect relationship maintenance on the basis of a network evolution perspective, and demonstrate how this effect can be influenced by cooperation length and structural holes.

Design/methodology/approach

Based on a sample of 122 matched pairs of the upstream and downstream supply chain from the Chinese paper-making industry, which is in urgent requirement of green strategies due to high pollution and resource consumption.

Findings

This study theoretically and empirically indicates that green strategies may have a positive impact on relationship maintenance. In addition, this effect can be positively moderated by cooperation length, but negatively moderated by structural holes.

Originality/value

This study uncovers the impact of green strategies on relationship maintenance by proposing a network evolution perspective, which could solve its conflicting effects in a specific context and move extant research a step forward.
“Going on a sensory adventure, a touchy subject?”: investigating haptic technology and consumer adventure orientation
Authors: Mulcahy Rory Francis , Riedel Aimee
Published: September 2021

Purpose

The purpose of this paper is twofold. First, it seeks to extend service and retailers understanding of how the inclusion of haptics can gamify digital service experiences. Second, it seeks to understand the moderating role of consumers orientation towards adventure in service experiences.

Design/methodology/approach

This research adopts a two-study, 2 (haptic technology: present vs absent) × 2 (adventure orientation: high vs low) to test the proposed hypotheses (Study 1 n = 210, Study 2 n = 452). The data are tested using ANCOVA's and Hayes PROCESS Macro to investigate mean differences and the potential presence of two different moderated mediated relationships.

Findings

The results are consistent across the two experimental studies evidencing that the inclusion of haptics to gamify the service experience leads to significantly improved outcomes for service brands and channels. Further, the results demonstrate that the impact of haptics is greater for consumers with a lower, compared to higher, sense of adventure. Thus, the results demonstrate that whilst haptics improves consumers experiences with technological services overall, this is more prevalent for those who have “less sense of adventure”.

Originality/value

This paper sheds insight into the emerging area of haptic technology and is one of the first to specifically examine the impact of consumers “sense of adventure.”
In vivo, in vitro and in silico: an open space for the development of microbe‐based applications of synthetic biology
Authors: Danchin Antoine
Published: September 2021

Living systems are studied using three complementary approaches: living cells, cell‐free systems and computer‐mediated modelling. Progresses in understanding, allowing researchers to create novel chassis and industrial processes rest on a cycle that combines in vivo, in vitro and in silico studies. This design–build–test–learn iteration loop cycle between experiments and analyses combines together physiology, genetics, biochemistry and bioinformatics in a way that keeps going forward. Because computer‐aided approaches are not directly constrained by the material nature of the entities of interest, we illustrate here how this virtuous cycle allows researchers to explore chemistry which is foreign to that present in extant life, from whole chassis to novel metabolic cycles. Particular emphasis is placed on the importance of evolution.
Inflammation‐nutritional markers of peripheral blood could predict survival in advanced non‐small‐cell lung cancer patients treated with PD‐1 inhibitors
Authors: Pu Dan , Xu Qian , Zhou Lai‐Yan , Zhou Yu‐Wen , Liu Ji‐Yan , Ma Xue‐Lei
Published: September 2021

Background

Inflammation‐nutritional markers of peripheral blood are easily assessed and can predict survival. The aim of this study was to investigate the association between inflammation‐nutritional parameters and survival of anti‐programmed death‐1 (PD‐1) therapy in non‐small‐cell lung cancer (NSCLC) patients.

Methods

We performed a retrospective study from March 2017 to April 2020 in advanced NSCLC patients treated with PD‐1 inhibitors. Univariable and multivariable analyses were conducted to evaluate the relationship between peripheral blood parameters (absolute lymphocyte count [ALC], absolute neutrophil count [ANC], absolute monocyte count [AMC], absolute eosinocyte count [AEC], lactic dehydrogenase [LDH], plasma‐albumin [ALB], neutrophil/lymphocyte ratio [NLR], and platelet/lymphocyte ratio [PLR]) measured before therapy initiation and prognosis.

Results

Among 184 evaluable patients, 134 (72.8%) were male and the median age was 58 years (range 33–87) with 31 (16.8%) ≥70 years. An elevated ANC (≥7500/ul), NLR (≥5), and PLR (≥200) was significantly associated with worse objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS), while increased ALC (≥1000/ul) and ALB (≥3.5 g/dl) could significantly improve survival in terms of ORR, PFS, and OS. In multivariate analyses, higher AEC (≥150/ul) and AMC (≥650/ul) could significantly decrease the risk of death (hazard ratio [HR] 0.363, 95% confidence interval [CI] 0.141–0.931, p = 0.035; HR 0.370, 95% CI 0.203–0.675, p = 0.001). A higher NLR and PLR, and lower ALB were independent predictors of poor prognosis for OS (HR 1.964, 95% CI 1.027–3.755, p = 0.041; HR 4.255, 95% CI 2.364–7.658, p = 0.000; HR 1.962, 95% CI 1.213–3.174, p = 0.006, respectively).

Conclusion

Our research illustrated that pretreatment AEC, AMC, ALB, NLR, and PLR are independent predictors for survival in advanced NSCLC patients treated with PD‐1 inhibitors.
Combined effect of salinity and hypoxia in seedlings of two varieties of Panicum coloratum: Morphology, root system architecture, oxidative damage and antioxidant response
Authors: Lifschitz Mauro , Tommasino Exequiel , Zabala Juan Marcelo , Grunberg Karina , Ramos Julio Cesar , Tomás María Andrea
Published: September 2021

The effect of the combination of salinity and waterlogging may be additive, or alternatively, more or less detrimental than effects of them separately. Our objective was to evaluate the effects of waterlogging, salinity and the combination of both on seedlings of Panicum coloratum, a subtropical forage grass. Seedlings of cultivars Kapivera INTA (KA) and Klein (KL) were exposed to treatments in a controlled hydroponic experiment and several morphological and physiological variables evaluated. The effect of hypoxia was almost null when the plants were already in salinity. KA showed lower reduction than KL in shoot biomass. Both varieties showed synergistic effect of stresses, indicating that biomass production was less affected under the combined treatment than predicted from them separately. Root length, tips, forks and volume were reduced by saline exposure, while no differences in root architecture was noticeable between cultivars. Plants of KA increased leaf temperature in salinity. Nonenzymatic oxidative response and the activity of antioxidant enzymes increased in saline conditions and were lower in KA than in KL. Oxidative damage was equivalent between cultivars and among stress conditions. Proline content was comparable to control in hypoxia but increased significantly in saline conditions, with a higher response in KL than in KA. Increases in Na+ (over 900%) and decreases in K+ (50%) tissue concentration in salinity occurred only in KA. In general, P. coloratum proved more tolerant to hypoxia than to salinity or their combination, KA being more tolerant than KL. Findings provide basis to deepen research into tolerance mechanisms.
Loss of tumor protein 53 protects against alcohol‐induced facial malformations in mice and zebrafish
Authors: Fish Eric W. , Tucker Scott K. , Peterson Rachel L. , Eberhart Johann K. , Parnell Scott E.
Published: September 2021

Background

Alcohol exposure during the gastrulation stage of development causes the craniofacial and brain malformations that define fetal alcohol syndrome. These malformations, such as a deficient philtrum, are exemplified by a loss of midline tissue and correspond, at least in part, to regionally selective cell death in the embryo. The tumor suppressor protein Tp53 is an important mechanism for cell death, but the role of Tp53 in the consequences of alcohol exposure during the gastrulation stage has yet to be examined. The current studies used mice and zebrafish to test whether genetic loss of Tp53 is a conserved mechanism to protect against the effects of early developmental stage alcohol exposure.

Methods

Female mice, heterozygous for a mutation in the Tp53 gene, were mated with Tp53 heterozygous males, and the resulting embryos were exposed during gastrulation on gestational day 7 (GD 7) to alcohol (two maternal injections of 2.9 g/kg, i.p., 4 h apart) or a vehicle control. Zebrafish mutants or heterozygotes for the tp53zdf1 M214K mutation and their wild‐type controls were exposed to alcohol (1.5% or 2%) beginning 6 h postfertilization (hpf), the onset of gastrulation.

Results

Examination of GD 17 mice revealed that eye defects were the most common phenotype among alcohol‐exposed fetuses, occurring in nearly 75% of the alcohol‐exposed wild‐type fetuses. Tp53 gene deletion reduced the incidence of eye defects in both the heterozygous and mutant fetuses (to about 35% and 20% of fetuses, respectively) and completely protected against alcohol‐induced facial malformations. Zebrafish (4 days postfertilization) also demonstrated alcohol‐induced reductions of eye size and trabeculae length that were less common and less severe in tp53 mutants, indicating a protective effect of tp53 deletion.

Conclusions

These results identify an evolutionarily conserved role of Tp53 as a pathogenic mechanism for alcohol‐induced teratogenesis.
Intracranial infected collections and epidemiology in the top end, Northern Territory, Australia. A 10‐year case series
Authors: Yoon Joseph , O'Bryan Claire Maree , Maclachlan Liam , Redmond Michael
Published: September 2021

Background

The incidence of intracranial infected collections (IIC) ranges between 0.4 and 1.2/100 000 persons per year. There is anecdotal evidence that residents in Top End of the Northern Territory are at a greater risk of infections with protracted clinical presentations. To our knowledge, there is no study to date to explore IIC in the Top End.

Methods

Retrospective observational analysis of IIC in the Top End, Northern Territory, Australia from 2009 to 2019. International classification of disease code G06 was used to identify cases diagnosed at Royal Darwin, Gove District and Katherine Hospital with no restriction of age or gender.

Results

A total of 51 cases were identified. This equated to an incidence of 2.9 (95% CI 2.2–3.8) in 100 000 PPY. When separated into Indigenous and non‐Indigenous populations, the respective incidences were 8.65 (95% CI 6.2–12.1) and 1.1 (95% CI 0.7–1.9) in 100 000 PPY. The Indigenous population was at a significantly higher risk of IIC compared with non‐Indigenous Australians with a relative risk of 7.3 (P < 0.0001 95% CI 4.0–13.3). The most common aetiology was otogenic infections with all cases being identified in the Indigenous population. Comparison of other clinical parameters between the two populations were not statistically significant.

Conclusions

Within the limitations of a retrospective study, the incidence of IICs is higher in the Top End than reported elsewhere in the literature. This is particularly true for the Indigenous population.
Impact of rurality and ethnicity on complexity of acute diverticulitis in Northland, New Zealand
Authors: Varghese Chris , Lengyel Olivia , McGuinness Matthew James , Harmston Christopher
Published: September 2021

Background

Acute diverticulitis is a common general surgical condition associated with significant costs and healthcare burden. It is unknown if rurality represents a barrier to healthcare and whether ethnic disparities exist in Northland, New Zealand. This study, therefore, aims to assess the impact of rurality and ethnicity on complexity, management, and outcomes in patients with acute diverticulitis.

Methods

A retrospective observational study of all adults aged >18 years admitted with acute diverticulitis to any Northland District Health Board hospital between 1 January 2015 and 31 December 2019 was performed. Diverticulitis complexity was assessed using the modified Hinchey classification. The primary outcome was the effect of rurality and ethnicity on complexity of diverticulitis. Multivariable logistic regression was performed.

Results

A total of 397 patients (mean age 60.3 years (standard deviation (SD) 13.8); 48.7% female) were included. Overall, 134 patients had complicated diverticulitis. Rurality nor distance from the hospital were not associated with complexity of diverticulitis or clinical outcomes (p > 0.05). Maori patients presented younger than non‐Maori (mean 51 vs. 63 years, p < 0.001) but there was no difference in complications, management, or clinical outcomes (p > 0.05). On multivariable analysis, rurality status and Maori ethnicity were not associated with more complicated diverticulitis.

Conclusion

This study found that rurality and ethnicity were not significant predictors of the complexity of diverticulitis.
The role of transformational leadership and leaders’ skills for new agricultural cooperatives in post‐soviet countries
Authors: Hejkrlik Jiri , Chaloupkova Petra , Sokolska Tetyana
Published: September 2021

Team leadership plays a crucial role in the management of agricultural cooperatives, especially in post‐Soviet countries where farmers keep bad experiences from the collectivization of their farms. The main objective of the research was to investigate how important the role of leadership is in the process of establishing, initial sustaining of cooperation and members’ commitment among small farmers in Georgia, Moldova and Ukraine. Leadership was analysed from multiple perspectives using an explanatory sequential mixed approach involving quantitative and qualitative methods. We interviewed 293 cooperative leaders and members. The partial least squares structural equation model was used to examine the relationship between multiple constructs and variables. We concluded that leaders do differ in some of their characteristics from other members. They are the most active in the group, influencing all major decisions, playing a crucial role in trust‐building and group cohesion. Their skills and leadership style are significantly important for members’ commitment to the group's success. However, the dominance of group founders and lack of understanding of cooperative principles among members indicate some emerging challenges to the cooperatives’ sustainability and efficiency, and it is necessary to focus on the progressive professionalization and capacity building of leaders while maintaining a transformational leadership style.
Donor source and post‐transplantation cyclophosphamide influence outcome in allogeneic stem cell transplantation for GATA2 deficiency
Authors: Nichols‐Vinueza Diana X. , Parta Mark , Shah Nirali N. , Cuellar‐Rodriguez Jennifer M. , Bauer Thomas R. , West Robert R. , Hsu Amy P. , Calvo Katherine R. , Steinberg Seth M. , Notarangelo Luigi D. , Holland Steven M. , Hickstein Dennis D.
Published: September 2021

GATA2 deficiency was described in 2011, and shortly thereafter allogeneic hematopoietic stem cell transplantation (HSCT) was shown to reverse the hematologic disease phenotype. However, there remain major unanswered questions regarding the type of conditioning regimen, type of donors, and graft‐versus‐host disease (GVHD) prophylaxis. We report 59 patients with GATA2 mutations undergoing HSCT at National Institutes of Health between 2013 and 2020. Primary endpoints were engraftment, reverse of the clinical phenotype, secondary endpoints were overall survival (OS), event‐free survival (EFS), and the incidence of acute and chronic GVHD. The OS and EFS at 4 years were 85·1% and 82·1% respectively. Ninety‐six percent of surviving patients had reversal of the hematologic disease phenotype by one‐year post‐transplant. Incidence of grade III‐IV aGVHD in matched related donor (MRD) and matched unrelated donor recipients (URD) patients receiving Tacrolimus/Methotrexate for GVHD prophylaxis was 32%. In contrast, in the MRD and URD who received post‐transplant cyclophosphamide (PT/Cy), no patient developed grade III‐IV aGVHD. Six percent of haploidentical related donor (HRD) recipients developed grade III‐IV aGVHD. In summary, a busulfan‐based HSCT regimen in GATA2 deficiency reverses the hematologic disease phenotype, and the use of PT/Cy reduced the risk of both aGVHD and cGVHD.
Design, synthesis, and biological evaluation of urea‐based ROCK2 inhibitors
Authors: Wang Linan , Qi Junhui , Fan Meixia , Yao Lei
Published: September 2021

A series of urea‐based ROCK2 inhibitors were design and synthesized. The inhibitory activity on ROCK2 was screened by enzyme‐linked immunosorbent assay (ELISA). The study results showed that the urea derivatives exhibited certain ROCK2 inhibitory activity. The most potent compound 10p showed ROCK2 inhibitory activity with the IC50 value of 0.03 μM. A preliminary structure‐activity relationship was then summarized. The molecular docking studies showed that further optimization needs to conduct to obtain more potent ROCK inhibitors.
What’s in a word? Cross‐linguistic influences on Spanish–English and Chinese–English bilingual children’s word reading development
Authors: Sun Xin , Zhang Kehui , Marks Rebecca A. , Nickerson Nia , Eggleston Rachel L. , Yu Chi‐Lin , Chou Tai‐Li , Tardif Twila , Kovelman Ioulia
Published: September 2021

This study investigates the cross‐linguistic transfer of literacy skills in Spanish–English, Chinese–English bilingual, and English monolingual children (N = 283, 5–10 years). Research question 1 examines English literacy and asks how phonological and morpho‐semantic skills contribute to word reading as a function of children's language background. Structural equation modeling revealed contrasting bilingual effects: compared to English monolinguals, Spanish–English bilinguals relied more on phonological awareness in word reading, whereas Chinese–English bilinguals relied more on lexical knowledge. Research question 2 examines relations between bilinguals’ heritage language proficiency and English literacy. Results revealed direct and indirect effects of heritage language meta‐linguistic skills on English word reading. The study yields implications for reading theories and instructional practices in optimizing literacy in linguistically diverse children.
Electroencephalographic neurofeedback as a tool for reducing harm and risk associated with alcohol use disorder: A critical review
Authors: Lima Karla Helene Marques , Gomes July Silveira , Tucci Adriana Marcassa
Published: September 2021

Issues

Alcohol use disorder (AUD) causes the highest harms around the world. Many people use alcohol to reduce stress and anxiety, considered as risk factors for AUD. Chronic alcohol use leads to changes in the reward system and the high level of stress may exacerbate neuroendocrine responses. Electroencephalographic (EEG) neurofeedback shows reduction of stress, anxiety and alcohol abuse and it could be an important tool for reducing harm and risk associated with AUD. The aim of this paper is to review the studies that investigated the effects of EEG neurofeedback in subjects with AUD and it proposes to discuss this intervention as a tool for reducing harm and risk in AUD.

Approach

Medline, PsycINFO and LILACS databases were searched and appropriated terms were used. Inclusion criterion was adopted. The year of publication was not limited because of the scarce number of studies. Eighty‐two papers returned and eight were included. A critical review was conducted.

Key Findings

Most of the papers analysed used the alpha/theta protocol to reduce the ‘hyperexcitation’ of the nervous system. This protocol provides relaxation, decreases anxiety or stress, prevents alcohol relapse, maintains abstinence and increases the feeling of well‐being.

Implications

EEG neurofeedback has important effects on AUD and anxiety or stress. Studies reinforce the use of EEG neurofeedback as an alternative tool for reducing harm and risk in AUD.

Conclusion

EEG neurofeedback is an intervention to treat AUD, specifically, to reduce harm and risk. However, more randomised studies are necessary to consolidate the effectiveness of the technique.
Stem‐cell based, machine learning approach for optimizing natural killer cell‐based personalized immunotherapy for high‐grade ovarian cancer
Authors: Esmail Sally , Danter Wayne R.
Published: September 2021

Advanced high‐grade serous ovarian cancer continues to be a therapeutic challenge for those affected using the current therapeutic interventions. There is an increasing interest in personalized cancer immunotherapy using activated natural killer (NK) cells. NK cells account for approximately 15% of circulating white blood cells. They are also an important element of the tumor microenvironment (TME) and the body's immune response to cancers. In the present study, DeepNEU‐C2Rx, a machine learning platform, was first used to create validated artificially induced pluripotent stem cell simulations. These simulations were then used to generate wild‐type artificially induced NK cells (aiNK‐WT) and TME simulations. Once validated, the aiNK‐WT simulations were exposed to artificially induced high‐grade serous ovarian cancer represented by aiOVCAR3. Cytolytic activity of aiNK was evaluated in presence and absence of aiOVCAR3 and data were compared with the literature for validation. The TME simulations suggested 26 factors that could be evaluated based on their ability to enhance aiNK‐WT cytolytic activity in the presence of aiOVCAR3. The addition of programmed cell death‐1 inhibitor leads to significant reinvigoration of aiNK cytolytic activity. The combination of programmed cell death‐1 and glycogen synthase kinase 3 inhibitors showed further improvement. Further addition of ascitic fluid factor inhibitors leads to optimal aiNK activation. Our data showed that NK cell simulations could be used not only to pinpoint novel immunotherapeutic targets to reinvigorate the activity of NK cells against cancers, but also to predict the outcome of targeting tumors with specific genetic expression and mutation profiles.
Temperature increase and frost decrease driving upslope elevational range shifts in Alpine grouse and hares
Authors: Schai‐Braun Stéphanie C. , Jenny Hannes , Ruf Thomas , Hackländer Klaus
Published: September 2021

Global climate change has led to range shifts in plants and animals, thus threatening biodiversity. Latitudinal shifts have been shown to be more pronounced than elevational shifts, implying that northern range edge margins may be more capable to keeping pace with warming than upper elevational limits. Additionally, global climate change is expected to disadvantage habitat specialists. In the Alps, climatic variation along the elevation gradient allows the coexistence of habitat specialists and generalists. Alpine species are anticipated to adapt their elevational ranges to the change of various climate variables caused by global climate change. Regional differences might buffer elevational shifts. Furthermore, distinct climate variables might differently affect the shifts of habitat specialists and generalists. To study the effect of climate change on Alpine species, we analysed hunting bag, climate and biogeographical data of two grouse species (Tetrao tetrix and Lagopus muta) and two hare species (Lepus timidus varronis and L. europaeus) in Grisons, Switzerland, over a period of 30 years. Our results based on 84,630 harvested specimens were as follows: (1) only three out of seven climate variables changed significantly within the study period. (2) The grouse species significantly shifted towards higher elevations, whereas the hare species only shifted in their minimum/maximum elevations. (3) Hunting elevation of habitat generalists increased more than in habitat specialists. (4) The elevational shifts were mostly related to the number of frost days. (5) Hunting elevation increased especially in the southern biogeographical region. To conclude, all four taxa respond to climate change but habitat generalists more rapidly than habitat specialists. The range shift to higher elevations due to global climate change will lead to a reduction in habitat availability for snow‐adapted species. Climate change is thus a serious threat to alpine biodiversity. Regions rich in alpine habitats will have an increased responsibility to conserve these species.
The economic effects of improved precipitation forecasts in the United States due to better commuting decisions
Authors: Hartman Brad , Cutler Harvey , Shields Martin , Turner Dave
Published: September 2021

Each year the U.S. government makes significant investments in improving weather forecasts from numerical weather prediction models that are run operationally within the National Weather Service. Although the primary purpose is saving lives and property, more accurate forecasts can create substantial efficiency gains when they elicit improved behavioral responses. One example involves commuters, who make daily decisions about when to leave for work based, in part, on expected road conditions. When workers account for potential weather delays, economic losses due to missed work time are reduced. Economists have often looked at such questions with cost‐loss models, a partial equilibrium approach investigating gains to individual agents. We extend this idea to examine economy‐wide effects, embedding a behavioral model of time allocation with improved information into eight regional computable general equilibrium models of the US economy. Our primary mechanism is that reductions in lost work time lead to gains in firm‐level output. This study evaluates the economic impact of improvements to the High‐Resolution Rapid Refresh weather forecast models over three different versions on commuting. Aggregating results from comparisons between old and new versions of the HRRR for 206 metropolitan statistical areas, we find that forecasting improvements lead to smaller losses in work time, creating notable gains to the U.S. economy.
Ties that bind: An inclusive feminist approach to subvert gendered “othering” in times of crisis
Authors: Abdellatif Amal , Gatto Mark , O'Shea Saoirse , Yarrow Emily
Published: September 2021

The COVID‐19 pandemic, as an ongoing societal crisis, compounds pre‐existing intersectional inequalities. Since the start of this crisis, those on the margins—women, single parents, LGBTQ+, Black, Asian, and Minority Ethnic peoples—and those living in precarity and poverty found themselves increasingly “othered.” As a group of academics who encounter gendered reality in disparate ways, we unite through this paper to prioritize a collective ethic of care as a counter‐narrative to the “business as usual” rhetoric that endures as our oppressive reality. In responding to this special issue, a (dis)embodied alterethnographical text is offered, encompassing four evocative reflections on symbolic annihilation to “unmute” our individual voices. We present an inclusive discussion to connect our disconnected otherness, collectively resisting the dominant, patriarchal narratives, through non‐linear, “messy writing.” Our contribution is threefold. First, we empirically contribute to dismantling heteronormative binarism by reclaiming our collective voices as a loud rebuttal to hegemony. Second, through collective conceptualizations of gendered crisis, we problematize theorizing gender from a unified conceptual lens to demonstrate the importance of an inclusive approach to feminism. Finally, a collective discussion of our cumulative experiences, contributes to the writing differently agenda, subverting the limitations of the encountered gender binaries.
Evaluating the ability of occurrence models to predict nest locations and associated vegetation
Authors: Fogarty Frank A. , Fleishman Erica , Zillig Martha W.
Published: September 2021

Occurrence models are frequently used to infer characteristics of habitat and inform management plans for large areas, but the extent to which these models predict reproduction, or the environmental characteristics associated with reproduction, is uncertain. We examined whether occurrence models based on point‐count data, and vegetation attributes within 50 m of presences, predicted the locations where birds were nesting in the Great Basin, USA. This work has practical relevance given that occurrence data require less time and effort to collect than direct measures of reproduction. We hypothesized that occurrence models would better characterize where two nest stratum generalists, Brewer's Sparrow Spizella breweri and Green‐tailed Towhee Pipilo chlorurus, nest than where a nest stratum specialist, American Dusky Flycatcher Empidonax oberholseri, nests. First, we compared which environmental covariates were associated with occurrence, via a model fitted to point‐count data, and nest locations, via a model fitted to data from confirmed nests. Second, we used data on the vegetation within 50 m of known nests to evaluate whether predictions from our occurrence model accurately classified the presence of nests. Third, we examined whether vegetation within 5 m of a known nest differed from vegetation at randomly chosen locations of equal size within 20–80 m of the nest. Occurrence models classified nest locations with relatively high accuracy for Brewer's Sparrow and American Dusky Flycatcher, and with moderate accuracy for Green‐tailed Towhee. Vegetation within 5 m of nests differed from that of random locations within 20–80 m, suggesting that even the nest stratum generalists based nest selection on fine‐grained attributes. Models that rely on point‐count data to examine species–habitat relationships assume that occupancy indicates breeding activity. Our results suggest that for some species, this is a valid assumption, although it is probably conditional on a well‐fitted occurrence model.
Audit practice: A straightforward trade or a complex system?
Authors: Barac Karin , Plant Kato , Kunz Rolien , Kirstein Marina
Published: September 2021

Auditors' skills and ways of working must adapt to constantly changing conditions in the workplace, and the COVID‐19 pandemic has brought further complexity. This paper uses a complexity theory lens to investigate changes in audit practice in recent years. A qualitative research method, using semi‐structured interviews, was applied: first to investigate how audit practice (skillsets and ways of working) needs to be reformed and second to suggest implications for audit practice stemming from a disruptive macro‐level event such as the current COVID‐19 pandemic. It was found that audit firms are framed as complex adaptive systems and new skillsets and ways of working in audit practice are well known for their adaptation, co‐evolution and emerging behaviours, which include virtual audits and remote working that have been brought about by the COVID‐19 pandemic.