bluuebunny/crossref_metadata_2025 huggingface dataset:
Antizyme inhibitor 2 (AZIN2) associates with better prognosis of head and neck minor salivary gland adenoid cystic carcinoma
Authors: Hämetoja Hanna , Andersson Leif C. , Mäkitie Antti , Bäck Leif , Hagström Jaana , Haglund Caj
Published: May 2021

The key regulator of the polyamine biosynthetic pathway is ornithine decarboxylase (ODC). ODC is activated by antizyme inhibitor 1 (AZIN1) and 2 (AZIN2). AZIN1 and recently AZIN2 have been related to cancer; however, their functions in adenoid cystic carcinoma (ACC) have not been studied. We performed immunohistochemical study on minor salivary and mucous gland ACC tissue samples of patients treated at the Helsinki University Hospital (Helsinki, Finland) during 1974–2012. We scored AZIN1 and 2 immunoexpression in 42 and 45 tumor tissue samples, respectively, and correlated them with clinicopathological factors and survival. Enhanced AZIN2 expression was associated with better survival. In addition, both AZINs were seen more commonly in cribriform and tubular than in solid growth patterns. AZIN1 expression did not correlate with the studied clinicopathological factors. It seems that AZIN2 expression is higher in cancer tissue with secretory functions. In ACC tissue, high AZIN2 expression could be related to well‐differentiated histological type which still has a functioning vesicle transportation system. Thus, AZIN2 could be a prognostic factor for better survival of ACC patients.
Delta‐globin gene expression improves sickle cell disease in a humanised mouse model
Authors: Porcu Susanna , Simbula Michela , Marongiu Maria F. , Perra Andrea , Poddie Daniela , Perseu Lucia , Kowalik Marta A. , Littera Roberto , Barella Susanna , Caria Cristian A. , Demartis Franca R. , Ristaldi Maria S.
Published: May 2021

Sickle cell disease (SCD) is a widespread genetic disease associated with severe disability and multi‐organ damage, resulting in a reduced life expectancy. None of the existing clinical treatments provide a solution for all patients. Gene therapy and fetal haemoglobin (HbF) reactivation through genetic approaches have obtained promising, but early, results in patients. Furthermore, the search for active molecules to increase HbF is still ongoing. The delta‐globin gene produces the delta‐globin of haemoglobin A2 (HbA2). Although expressed at a low level, HbA2 is fully functional and could be a valid anti‐sickling agent in SCD. To evaluate the therapeutic potential of a strategy aimed to over‐express the delta‐globin gene in vivo, we crossed transgenic mice carrying a single copy of the delta‐globin gene, genetically modified to be expressed at a higher level (activated), with a humanised mouse model of SCD. The activated delta‐globin gene gives rise to a consistent production of HbA2, effectively improving the SCD phenotype. For the first time in vivo, these results demonstrate the therapeutic potential of delta‐globin, which could lead to novel approaches to the cure of SCD.
Phosphorylation‐mediated signalling in flowering: prospects and retrospects of phosphoproteomics in crops
Authors: Arefian Mohammad , Bhagya N. , Prasad T. S. Keshava
Published: May 2021

Protein phosphorylation is a major post‐translational modification, regulating protein function, stability, and subcellular localization. To date, annotated phosphorylation data are available mainly for model organisms and humans, despite the economic importance of crop species and their large kinomes. Our understanding of the phospho‐regulation of flowering in relation to the biology and interaction between the pollen and pistil is still significantly lagging, limiting our knowledge on kinase signalling and its potential applications to crop production. To address this gap, we bring together relevant literature that were previously disconnected to present an overview of the roles of phosphoproteomic signalling pathways in modulating molecular and cellular regulation within specific tissues at different morphological stages of flowering. This review is intended to stimulate research, with the potential to increase crop productivity by providing a platform for novel molecular tools.
SPASOS 1.1: a program for the inference of ancestral shape ontogenies
Authors: Catalano Santiago Andrés , Segura Valentina , Vera Candioti Florencia
Published: May 2021

We recently published a method to infer ancestral landmark‐based shape ontogenies that takes into account the possible existence of changes in developmental timing. Here we describe SPASOS, a software to perform that analysis. SPASOS is an open‐source Windows program written in C. Input data include landmark coordinates for each specimen –with the corresponding information about developmental timing– and a phylogenetic tree showing the relationships among the species sampled. As output, the program produces image files for an easy visualization of the results and data files useful for post‐processing. The program incorporates an interpolating function, based on weighting moving averages, which allows analysis of data with scarce information along the ontogenetic trajectory. An empirical evaluation of this function showed its suitability to fill in incomplete ontogenetic trajectories. Finally, we present the results of a reanalysis in SPASOS of a published dataset, where changes in developmental timing were originally inferred by considering PCA scores as shape variables. Both approaches retrieved the same four largest changes in developmental timing, but differed in the ancestral shapes inferred.
The value of cytology in distinguishing malignant mesothelioma: An institutional experience of 210 cases reclassified according to the International System for Reporting Serous Fluid Cytopathology (ISRSFC)
Authors: Straccia Patrizia , Magnini Daniele , Trisolini Rocco , Lococo Filippo , Chiappetta Marco , Cancellieri Alessandra
Published: May 2021

Objective

Malignant mesothelioma (MM) is usually diagnosed by histological examination of tissue samples; however, effusion cytology offers an opportunity to identify a strong possibility for mesothelioma diagnosis at an early stage. We conducted a retrospective analysis of cytological specimens from a large series of histologically proven MM diagnosed over 19 years. The cases were reviewed and reclassified according to the International System for Reporting Serous Fluid Cytopathology (ISRSFC).

Methods

A total of 450 cases were identified. Cytological analysis was present in 210 patients (164 pleural and 46 peritoneal effusions). All cases were reviewed and reclassified according to the proposed ISRSFC scheme. A comparison among the cytomorphological features was made throughout the different diagnostic categories.

Results

The 210 cases were histologically diagnosed as follows: 192 (91.4%) cases had an epithelioid type and 18 (8.6%) had a sarcomatoid subtype of MM. The cytological cases were reclassified as follows: 2 (0.9%) as non‐diagnostic (ND), 81 (38.6%) as negative for malignancy (NFM), 4 (1.9%) as atypia of undetermined significance (AUS), 11 (5.2%) as suspicious for malignancy (SFM), 112 (53.4%) as malignant (MAL). Sarcomatoid cells in the MAL category were characterised cytomorphologically by more pronounced discohesion. In comparison with the epithelioid subtype, the tumour cells appeared solitary with moderate or marked nuclear pleomorphism, and irregular chromatin.

Conclusions

It is important to recognise the cytological characteristics of this aggressive entity to suggest an early and precise possible diagnosis. Morphological features, coupled with clinico‐radiological data may help the clinicians in adequately managing the patients.
Risk of diabetic macular oedema with sodium‐glucose cotransporter‐2 inhibitors in type 2 diabetes patients: A multi‐institutional cohort study in Taiwan
Authors: Su Yu‐Chen , Shao Shih‐Chieh , Lai Edward Chia‐Cheng , Lee Chaw‐Ning , Hung Ming‐Jui , Lai Chi‐Chun , Hsu Sheng‐Min , Hung Jia‐Horung
Published: May 2021

Aims

To investigate the risk of diabetic macular oedema (DMO) associated with the use of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM).

Materials and Methods

We conducted a retrospective cohort study by analysing a large multi‐institutional electronic medical records database in Taiwan. We included adult patients with T2DM without DMO newly receiving either SGLT2 inhibitors or glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) during the period 2016 to 2018. We used propensity scores with inverse probability of treatment weighting to generate comparable groups. The study outcome was incident DMO, determined by clinical diagnosis during outpatient visits or admissions. We followed patients from the index date to either DMO occurrence, last clinical visit, patient death, or December 31, 2020. We performed Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of DMO.

Results

We included 9986 new users of SGLT2 inhibitors (mean [SD] age 59.6 (12.1) years, median [interquartile range {IQR}] glycated haemoglobin [HbA1c] 70 (61‐81)mmol/mol, estimated glomerular filtration rate [eGFR] 89.1 [71.4‐108.7] mL/min/1.73 m2 and urine albumin‐creatinine ratio [UACR] 26.1 [9.7‐117.6] mg/g) and 1067 new users of GLP‐1RAs (mean [SD] age 58.4 (41.5) years, median [IQR] HbA1c 73 [64‐84] mmol/mol, eGFR 91.6 [68.6‐114.0] mL/min/1.73 m2 and UACR 37.6 [11.1‐153.2] mg/g) with similar baseline characteristics. Lower DMO risks were observed among patients newly receiving SGLT2 inhibitors (7.9/1000 person‐years), compared to those receiving GLP‐1RAs (10.7/1000 person‐years) with an HR of 0.75 (95% CI 0.64‐0.88).

Conclusions

Our findings suggest use of SGLT2 inhibitors was associated with lower risk of DMO in T2DM patients in clinical practice, compared to use of GLP‐1RAs. Future studies are necessary to confirm this observation.
Prevalence and follow‐up of subclinical rheumatic heart disease among asymptomatic school children in a north‐western district of India based on the World Heart Federation echocardiographic criteria
Authors: Choudhary Dinesh , Panwar Sadik Raja , Gupta Bal Kishan , Panwar Raja Babu , Gupta Rajeev , Bhaya Maneesha , Beniwal Rajesh , Raja Panwar Vasim , Sharma Arvind , Gupta Jigyasa , Nanda Navin C.
Published: May 2021

Background

The present study is based on the World Heart Federation (WHF) echocardiographic criteria to assess the prevalence of subclinical rheumatic heart disease (RHD) and elucidate evolution of the disease when the cases were placed on appropriate antibiotic prophylaxis and regular follow‐up. The prevalence of subclinical RHD reported by previous active surveillance studies among asymptomatic school children is not comparable to our study because of major differences in screening methods.

Methods

A random inclusion strategy was adopted to recruit urban and rural school children of Bikaner district in the state of Rajasthan, India. The diagnosis of RHD was based on the echocardiographic criteria proposed by the WHF. All studies were reported on‐site by a single experienced cardiologist and the digitally preserved studies were reported by a second cardiologist off‐site. The final diagnosis was made by consensus. The second echocardiogram was performed for cases diagnosed with RHD after two years from start of study to document early evolution of the disease with ongoing antibiotic prophylaxis.

Results

A high prevalence of subclinical RHD was observed in the study population. Pathological mitral and/or aortic valve regurgitation was the commonest lesion, and a significant proportion of cases improved while on regular antibiotic prophylaxis. No case showed fixity of leaflets/ stenosis.

Conclusion

The prevalence of subclinical RHD is high in the study population, and the disease seems to regress over time in the presence of appropriate antibiotic prophylaxis.
Local immune microenvironment of skin may play an important role in the development of pretibial myxedema
Authors: Chen Xiaoying , Dong Jiaoyun , Zhang Li , Zhao Xiaoqing , Shi Ruofei , Pan Meng , Zheng Jie
Published: May 2021

Pretibial myxedema (PTM), characterized by the accumulation of glycosaminoglycans in dermis is an autoimmune skin disorder, which is almost always associated with Graves’ disease (GD). Although fibroblast stimulated by thyroid‐stimulating hormone receptor (TSHR) antibody, cytokines and growth factors have been postulated as target of the autoimmune process in the dermopathy, the pathogenesis of PTM remains unclear. We hypothesize that the local immune microenvironment of the skin including the antigens and antibodies, T cells, B cells, plasma cells and fibroblasts may play an important role in the development of PTM.

Results obtained on PTM patients indicate increased thyroid‐stimulating hormone receptor antibodies (TRAb) in the blood positively correlate with the dermal thickness of the lesions. Further analysis shows that there were more CD3+ T cells and CD20+ B cells in the skin lesions. These T and B cells are in close contact, indicating that inducible skin‐associated lymphoid tissue (iSALT) may be formed in the area. In addition, we found that the infiltrating plasma cells can secrete TRAb, proving that B cells in the skin other than the thyroid are an additional source of TSHR antibodies. Meanwhile, the T and B cells in the skin or skin homogenate of patients can promote the proliferation of pretibial fibroblasts. In conclusion, our results provide evidence that the local immune microenvironment of the skin may play an important role in the development of PTM.
Prognosis of intrahepatic cholangiocarcinoma stratified by albumin–bilirubin grade
Authors: Kaneko Shun , Kurosaki Masayuki , Tsuchiya Kaoru , Yasui Yutaka , Inada Kento , Kirino Sakura , Yamashita Koji , Osawa Leona , Hayakawa Yuka , Sekiguchi Shuhei , Higuchi Mayu , Takaura Kenta , Maeyashiki Chiaki , Tamaki Nobuharu , Itakura Jun , Takahashi Yuka , Nakanishi Hiroyuki , Asano Daisuke , Irie Takumi , Kawachi Yasuyuki , Izumi Namiki
Published: May 2021

Aim

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy. However, the characteristics and prognosis of ICC is not well known. This study aims to reveal the relationship between liver function and prognosis of ICC.

Methods

A total of 83 ICC patients were recruited retrospectively from March 2009 to August 2020. Child–Pugh (CP) and albumin–bilirubin (ALBI) scores were used to assess liver function. The extent of portal vein tumor thrombosis (PVTT) was classified from Vp0 to Vp4. The end‐point for this analysis was overall survival (OS).

Results

The median age was 72 (44–88) years, 48 patients were male (57.8%), and 70 patients were classified as CP grade A (84.3%). At baseline, chronic liver disease (hepatitis B, 9.6%; hepatitis C, 15.7%; alcoholic liver disease, 9.6%; and nonalcoholic fatty liver disease, 4.8%) were diagnosed. The median OS of all ICC patients was 21.2 months. A total of 27 patients underwent surgical resection; these patients showed a longer median OS compared to those who did not undergo surgery (50.8 months vs. 5.5 months, p < 0.001). The prognosis of patients with ICC can be stratified by ALBI grade (grade 1, 54.3 months; grade 2a, 8.4 months; grade 2b, 3.9 months; and grade 3, 1.4 months; p < 0.001) and the extent of PVTT (Vp0, 54.3 months; Vp1/2, 8.4 months; and Vp3/4, 3.9 months; p = 0.0039).

Conclusion

In this study, viral hepatitis (25.3%) was identified as the most prevalent background liver disease of ICC. Assessing liver function using ALBI grade is useful for stratifying the prognosis of patients with ICC.
Sharing administrative health data with private industry: A report on two citizens' juries
Authors: Street Jackie , Fabrianesi Belinda , Adams Carolyn , Flack Felicity , Smith Merran , Carter Stacy M. , Lybrand Sean , Brown Anthony , Joyner Serena , Mullan Judy , Lago Luise , Carolan Lucy , Irvine Katie , Wales Coralie , Braunack‐Mayer Annette J.
Published: May 2021

Background

There is good evidence of both community support for sharing public sector administrative health data in the public interest and concern about data security, misuse and loss of control over health information, particularly if private sector organizations are the data recipients. To date, there is little research describing the perspectives of informed community members on private sector use of public health data and, particularly, on the conditions under which that use might be justified.

Methods

Two citizens' juries were held in February 2020 in two locations close to Sydney, Australia. Jurors considered the charge: ‘Under what circumstances is it permissible for governments to share health data with private industry for research and development?’

Results

All jurors, bar one, in principle supported sharing government administrative health data with private industry for research and development. The support was conditional and the juries' recommendations specifying these conditions related closely to the concerns they identified in deliberation.

Conclusion

The outcomes of the deliberative processes suggest that informed Australian citizens are willing to accept sharing their administrative health data, including with private industry, providing the intended purpose is clearly of public benefit, sharing occurs responsibly in a framework of accountability, and the data are securely held.

Patient and Public Contribution

The design of the jury was guided by an Advisory Group including representatives from a health consumer organization. The jurors themselves were selected to be descriptively representative of their communities and with independent facilitation wrote the recommendations.
Business as unusual: medical oncology services adapt and deliver during COVID‐19
Authors: Travers Avraham , Adler Kim , Blanchard Gillian , Bonaventura Tony , Charlton Julie , Day Fiona , Healey Laura , Kim Sang , Lombard Janine , Mallesara Girish , Mandaliya Hiren , Navani Vishal , Nordman Ina , Paterson Robin , Plowman Louise , Quah Gaik Tin , Scalley Michael , Shrestha Prajwol , Tailor Bharti , van der Westhuizen Andre , Zhang Betty , Gedye Craig , Lynam James
Published: May 2021

Background

The COVID‐19 pandemic has challenged cancer care globally, introducing resource limitations and competing risks into clinical practice.

Aims

To describe the COVID‐19 impact on medical oncology care provision in an Australian setting.

Methods

Calvary Mater Newcastle and Newcastle Private Hospital medical oncology data from 1 February to 31 April 2019 versus 2020 were retrospectively analysed.

Results

Three hundred and sixty‐four inpatient admissions occurred in 2020, 21% less than in 2019. Total inpatient days decreased by 22% (2842 vs 2203). April was most impacted (36% and 44% fewer admissions and inpatient days respectively). Mean length of stay remained unchanged (6.4 vs 6.2 days, P = 0.7). In all, 5072 outpatient consultations were conducted, including 417 new‐patient consultations (4% and 6% increase on 2019 respectively). Telephone consultations (0 vs 1380) replaced one‐quarter of face‐to‐face consultations (4859 vs 3623, −25%), with minimal telehealth use (6 vs 69). Day Treatment Centre encounters remained stable (3751 vs 3444, −8%). The proportion of new patients planned for palliative treatment decreased (35% vs 28%, P = 0.04), observation increased (16% vs 23%, P = 0.04) and curative intent treatment was unchanged (both 41%). Recruiting clinical trials decreased by one‐third (45 vs 30), two trials were activated (vs 5 in 2019) and 45% fewer patients consented to trial participation (62 vs 34).

Conclusion

Our medical oncology teams adapted rapidly to COVID‐19 with significant changes to care provision, including fewer hospital admissions, a notable transition to telephone‐based outpatient clinics and reduced clinical trial activity. The continuum of care was largely defended despite pandemic considerations and growing service volumes.
Hyperferritinaemia and iron overload in Asian patients: lessons from an Australian tertiary centre experience
Authors: Con Danny , Nicoll Amanda J.
Published: May 2021

Iron overload is described in Asian patients but presents with a different phenotype and genotype compared to Caucasian patients. We retrospectively identified 64 Asian patients and compared them to 64 matched non‐Asian patients with at least one episode of serum ferritin >500 μg/L. Of the Asian patients, one (1.6%) had proven iron overload, while other common causes of hyperferritinaemia included recent blood transfusion (47%), acute infection (11%) and haematological malignancy (8%). A greater proportion of non‐Asian patients had hyperferritinaemia secondary to high alcohol intake. Iron overload is rare in Asians and unexplained hyperferritinaemia in Asian patients is more likely to be due to other factors.
Research trends in combinatorial optimization
Authors: Weinand Jann Michael , Sörensen Kenneth , San Segundo Pablo , Kleinebrahm Max , McKenna Russell
Published: May 2021

Real‐world problems are becoming highly complex and therefore have to be solved with combinatorial optimization (CO) techniques. Motivated by the strong increase in publications on CO, 8393 articles from this research field are subjected to a bibliometric analysis. The corpus of literature is examined using mathematical methods and a novel algorithm for keyword analysis. In addition to the most relevant countries, organizations, and authors as well as their collaborations, the most pertinent CO problems, solution methods, and application areas are presented. Publications on CO focus mainly on the development or enhancement of metaheuristics like genetic algorithms. The increasingly problem‐oriented studies deal particularly with real‐world applications within the energy sector, production sector, or data management, which are of increasing relevance due to various global developments. The demonstration of global research trends in CO can support researchers in identifying the relevant issues regarding this expanding and transforming research area.
Mitigating the impact of the ‘silos’ between the disability and aged‐care sectors in Australia: Development of a Best Practice Framework
Authors: Hussain Rafat , Parmenter Trevor , Wark Stuart , Janicki Matthew , Knox Marie , Hayhoe Nicola
Published: May 2021

Background

Although a ‘person‐centred focus’ is a legislated objective for both aged‐care and disability services sectors in Australia, evidence suggests limited translation into systems and practices due to entrenched silos. This paper proposes a Best Practice Framework to mitigate these silos.

Methods

Mixed‐methods research comprising key informant interviews with major stakeholders across both sectors; a survey of people with/without intellectual disability aged 60+ years; qualitative in‐depth interviews; and survey of health professionals.

Results

There is an urgent need to develop inter‐sectoral ‘integrated care systems’. Key components include choice in accommodation; regular assessment of health and well‐being indicators; development and adoption of nationally consistent policies/standards across integrated aged‐ and disability‐care sectors; improved strategies for workforce planning; and upskilling of existing staff including place‐based collaboration.

Conclusions

An integrated service model requires collaboration on broader public policy instruments, appropriate planning and resourcing. A strategic shift is required to ensure better quality person‐centred support systems.
Early success of COVID‐19 vaccines in nursing homes: Will it stick?
Authors: Ouslander Joseph G. , Saliba Debra
Published: May 2021

This editorial comments on the articles by Mor et al, Moore et al, Rudolph et al, and Domi et al. in this issue.
Skin cancer knowledge, attitudes, and practices among non‐medical skin care professionals: A narrative review of cross‐sectional and interventional studies
Authors: Pearlman Ross L. , Wilkerson Amanda H. , Ferris Taylor S. , Griffin David B. , Cobb Emily K. , McCowan Hannah K. , Bhattacharya Kaustuv , Leo Jonathan T. , Melton Sheree C. , Nahar Vinayak K.
Published: May 2021

Background

Skin cancers are the most common malignancies in the United States. Total body skin examination by a physician, especially a dermatologist, is the gold standard for detecting suspicious lesions that may require further evaluation. Non‐medical professionals (NMPs) including massage therapists, estheticians, hairdressers, and cosmetologists have the unique opportunity to frequently examine their client's skin outside of a clinical setting. By evaluating their knowledge of and comfort with evaluation of suspicious lesions, multiple studies have gauged the utility of patient encounters with NMPs for skin cancer detection. Several studies have also focused on assessment of intervention strategies for assessing and improving NMPs ability to detect suspicious lesions and to refer for physician evaluation when necessary.

Aims

To conduct a narrative review of skin cancer knowledge, attitudes, and practices among NMPs.

Patients/Methods

A systematic search of the databases yielded 16 studies for review. A total of 8 cross‐sectional studies examined the knowledge and attitudes of NMPs toward skin evaluation, and 8 studies assessed interventional strategies for improving NMPs’ ability to assess skin lesions for consideration of physician referral.

Results

This review finds that NMPs are open to the idea of examining the exposed body surfaces relevant to their work with clients and are willing to refer for physician evaluation when needed. Multiple interventional strategies have demonstrated success with educating NMPs on the importance of skin surveillance and the characteristic physical examination findings associated with skin cancers.

Conclusion

Strengthening the readiness of NMPs to examine their client's skin offers an opportunity to reduce time to skin cancer diagnosis, improve patient outcomes, and lower healthcare‐associated costs of skin cancer treatment.
Emotion: The forgotten component of legal socialization
Authors: Cole Lindsey M. , Kelley Donovan C. , Hennigan Paul J. , Rebellon Cesar J. , Van Gundy Karen T. , Cohn Ellen S.
Published: May 2021

Legal socialization researchers have largely ignored the importance of emotion in the legal socialization process and engagement in crime. The purpose of the current study was to argue the potential importance of moral emotions (e.g., guilt) in legal socialization and take a preliminary step to integrate an emotion component into an existing model. The current study investigated whether the moral emotion of guilt, using both proneness and anticipatory measures, would predict rule‐violating behavior (RVB) as part of the integrated cognitive legal socialization model. The study used survey data from 474 participants who were part of a longitudinal study of adolescent rule‐violating behavior. Results showed that guilt proneness functioned as a predictor of RVB in parallel with legal reasoning, while anticipatory guilt served as a mediator in parallel with normative attitude mediators. Enforcement status (i.e., feeling people should be punished for committing RVB) mediated the relation between guilt proneness and RVB, while normative status (i.e., approval for engaging in RVB) and anticipatory guilt mediated the relation between legal reasoning and RVB. These findings help to advance legal socialization by demonstrating the unique contribution of emotion in legal socialization theory and provide a foundation for future research in this area. The implications for the role of emotion in both the integrated cognitive legal socialization model and the procedural justice legal socialization model and future directions for further inquiry are discussed.
The aging general surgeon of rural America
Authors: Shelton Jarod , MacDowell Martin
Published: May 2021

Purpose

Nonmetropolitan communities are faced with health care professional shortages and prior reports suggest that general surgeons are no exception. The purpose of this brief is to evaluate the age difference and distribution of rural versus urban general surgeons to highlight the growing need to recruit medical students and residents for rural practice.

Methods

A secondary data analysis of residency graduated general surgeon demographics at the county level was performed using data from the Area Health Resource File. General surgeon demographic data were compared between nonmetropolitan and metropolitan areas.

Findings

The number of general surgeons practicing in rural communities is decreasing by a rate of approximately 0.5%‐1.0% annually. Moreover, the entry of younger (<35 years of age) general surgeons into rural counties (8.7%) was less than urban regions (12.1%). Rural general surgeons tended to be older than their urban peers, and on average, rural general surgeon age exhibits a negative skewed, platykurtic distribution.

Conclusions

Immediate action must be taken to generate more surgeons for rural practice. A failure to increase recruitment and retention of rural surgeons may have severe consequences on the health status of rural communities.
Relation between the severity of liver cirrhosis and neurological symptoms, nerve conduction study results, and motor unit number estimation
Authors: Gabr Reem M , El Salmawy Dina A , Basheer Mye A , khairy Marwa , Elkholy Saly H
Published: May 2021

Liver cirrhosis is a global health problem that can be associated with several neurological manifestations. We aimed to assessment of the relation between the severity of the liver cirrhosis and the neurological symptoms, nerve conduction studies (NCS), as well as detecting subclinical neuropathic affection using motor unit number estimation (MUNE) technique. This cross‐sectional study was conducted on 56 cirrhotic patients and 61 age‐ and sex‐matched healthy controls. Neurological manifestations, Child‐Pugh classification, Model for End‐Stage Liver Disease score, NCS and MUNE using a modified spike‐triggered averaging technique were studied. Forty‐five (80.3%) of the cirrhotic patients had neurological manifestations. Muscle cramps were the most frequently reported manifestation, followed by fatigue and then numbness. NCS abnormality was significantly related to the presence of neurological symptoms (p < 0.001) and not only to peripheral numbness. Only fatigue was significantly related to the lower MUNE values (p < 0.017). Child‐Pugh classification progression was significantly related to the presence of fatigue and abnormal NCS results (p < 0.001); no similar relation was detected between the Child‐Pugh classification and the MUNE value (p = 0.103). Higher MELD scores were significantly related to NCS abnormalities (p = 0.014) and negatively correlated, although not significantly, with the MUNE values (r = −0.246 and p = 0.067). The progression of liver cirrhosis was related to the presence of neurological manifestations and nerve conduction abnormalities. Nerve conduction abnormalities may be present even in the absence of clinical numbness. A decline in motor unit number could explain the pathophysiology of fatigue in cirrhotic patients.
Bronchial angiogenesis in horses with severe asthma and its response to corticosteroids
Authors: Millares‐Ramirez Esther M. , Lavoie Jean‐Pierre
Published: May 2021

Background

Severe asthma in horses is characterized by structural changes that thicken the lower airway wall, a change that is only partially reversible by current treatments. Increased vascularization contributes to the thickening of the bronchial wall in humans with asthma and is considered a potential new therapeutic target.

Objective

To determine the presence of angiogenesis in the bronchi of severely asthmatic horses, and if present, to evaluate its reversibility by treatment with corticosteroids.

Animals

Study 1: Bronchial samples from asthmatic horses in exacerbation (7), in remission (7), and aged‐matched healthy horses. Study 2: Endobronchial biopsy samples from asthmatic horses in exacerbation (6) and healthy horses (6) before and after treatment with dexamethasone.

Methods

Blinded, randomized controlled study. Immunohistochemistry was performed using collagen IV as a marker for vascular basement membranes. Number of vessels, vascular area, and mean vessel size in the bronchial lamina propria were measured by histomorphometry. Reversibility of vascular changes in Study 2 was assessed after 2 weeks of treatment with dexamethasone.

Results

The number of vessels and vascular area were increased in the airway walls of asthmatic horses in exacerbation (P = .01 andP = .02, respectively) and in remission (P = .02 andP = .04, respectively) when compared to controls. In Study 2, the differences observed between groups disappeared after 2 weeks of treatment with corticosteroids because of the increased number of vessels in healthy horses.

Conclusions and Clinical Importance

Angiogenesis contributes to thickening of the airway wall in asthmatic horses and was not reversed by a 2‐week treatment with corticosteroids.
Diagnosis, treatment, and outcome in a dog with systemic Mycoleptodiscus indicus infection
Authors: Crespo‐Szabo Sara M. , Stafford Jennifer R.
Published: May 2021

Objective

Describe the diagnosis, clinical course, and management of a dog with systemic Mycoleptodiscus indicus infection.

Case Summary

A 5‐year‐old male neutered Giant Schnauzer presented with left eye anterior uveitis, peripheral lymphadenopathy, hyperglobulinemia, anemia, and thrombocytopenia. A diagnosis of M. indicus infection was made based on histopathology and PCR. Treatment with itraconazole and terbinafine resulted in resolution of the hyperglobulinemia, anemia, thrombocytopenia, and peripheral lymphadenopathy. No evidence of fungal organisms was identified on lymph node, liver, or ocular histopathology after 7 months of treatment.

New or Unique Information Provided

This case is the first report of a systemic M. indicus infection in an apparently immunocompetent dog. Clinical resolution was achieved with systemic itraconazole and terbinafine.
TDP‐43 proteinopathy occurs independently of autophagic substrate accumulation and underlies nuclear defects in Niemann‐Pick C disease
Authors: Liu Elaine A. , Mori Erika , Hamasaki Fuko , Lieberman Andrew P.
Published: May 2021

Aims

Neuronal cytoplasmic inclusions of TAR‐DNA binding protein of 43 kDa (TDP‐43) are a pathological hallmark of diverse neurodegenerative disorders, yet the processes that mediate their formation and their functional significance remain incompletely understood. Both dysfunction in autophagy and neuroinflammation have been linked to TDP‐43 mislocalisation. Here, we investigate TDP‐43 proteinopathy in Niemann‐Pick type C disease (NPC), an autosomal recessive lysosomal storage disease (LSD) distinguished by the accumulation of unesterified cholesterol within late endosomes and lysosomes. NPC is characterised by neurodegeneration, neuroinflammation and multifocal disruption of the autophagy pathway.

Methods

We utilised immunohistochemistry, confocal microscopy, electron microscopy and biochemical and gene expression studies to characterise TDP‐43 pathology and autophagic substrate accumulation in Npc1‐deficient mice.

Results

In the NPC brain, cytoplasmic TDP‐43 mislocalisation was independent of autophagic substrate accumulation. These pathologies occurred in distinct neuronal subtypes, as brainstem cholinergic neurons were more susceptible to TDP‐43 mislocalisation, whereas glutamatergic neurons exhibited hallmarks of autophagic dysfunction. Furthermore, TDP‐43 mislocalisation did not co‐localise with markers of stress granules or progress to ubiquitinated aggregates over months in vivo, indicating a stable, early stage in the aggregation process. Neither microgliosis nor neuroinflammation were sufficient to drive TDP‐43 proteinopathy in the NPC brain. Notably, cytoplasmic TDP‐43 co‐localised with the nuclear import factor importin α, and TDP‐43 mislocalised neurons demonstrated nuclear membrane abnormalities and disruption of nucleocytoplasmic transport.

Conclusion

Our findings highlight the relationship between LSDs and TDP‐43 proteinopathy, define its functional importance in NPC by triggering nuclear dysfunction, and expand the spectrum of TDP‐43 pathology in the diseased brain.
Objectively measured chronic disease risk among food pantry patrons
Authors: Greer Anna E. , Faber Marilyn , Smith Gina , Pendley Sofia , Kamdar Nipa
Published: May 2021

Objectives and Design

This cross‐sectional, observational study examined the prevalence of objectively measured chronic disease risk factors among a diverse group of food pantry patrons.

Sample and Measurement

Public health nurses performed biometric screenings in community settings for 1,685 unduplicated adults attending food pantries.

Results

Over three fourths of participants (81.1%) were overweight or obese. High cholesterol and high blood pressure were detected in 38.4% and 37.7% of participants, respectively. Over half (58%) of the participants were referred to a local community health clinic for follow‐up services.

Conclusion

Interventions should target food pantry patrons to reduce the prevalence of chronic disease conditions among this vulnerable population.
Spectral signatures in the UV range can be combined with secondary plant metabolites by deep learning to characterize barley–powdery mildew interaction
Authors: Brugger Anna , Schramowski Patrick , Paulus Stefan , Steiner Ulrike , Kersting Kristian , Mahlein Anne‐Katrin
Published: May 2021

In recent studies, the potential of hyperspectral sensors for the analysis of plant–pathogen interactions was expanded to the ultraviolet range (UV; 200–380 nm) to monitor stress processes in plants. A hyperspectral imaging set‐up was established to highlight the influence of early plant–pathogen interactions on secondary plant metabolites. In this study, the plant–pathogen interactions of three different barley lines inoculated with Blumeria graminis f. sp. hordei (Bgh, powdery mildew) were investigated. One susceptible genotype (cv. Ingrid, wild type) and two resistant genotypes (Pallas 01, Mla1‐ and Mla12‐based resistance and Pallas 22, mlo5‐based resistance) were used. During the first 5 days after inoculation (dai) the plant reflectance patterns were recorded and plant metabolites relevant in host–pathogen interactions were studied in parallel. Hyperspectral measurements in the UV range revealed that a differentiation between barley genotypes inoculated with Bgh is possible, and distinct reflectance patterns were recorded for each genotype. The extracted and analysed pigments and flavonoids correlated with the spectral data recorded. A classification of noninoculated and inoculated samples with deep learning revealed that a high performance can be achieved with self‐attention networks. The subsequent feature importance identified wavelengths as the most important for the classification, and these were linked to pigments and flavonoids. Hyperspectral imaging in the UV range allows the characterization of different resistance reactions, can be linked to changes in secondary plant metabolites, and has the advantage of being a non‐invasive method. It therefore enables a greater understanding of plant reactions to biotic stress, as well as resistance reactions.
Exploring autonomic regulation in children with ADHD with and without comorbid anxiety disorder through three systematic levels of cardiac vagal control analysis: Rest, reactivity, and recovery
Authors: Robe Andreea , Păsărelu Costina‐Ruxandra , Dobrean Anca
Published: May 2021

Autonomic nervous system (ANS) dysregulation, characterized by reduced vagally mediated Heart Rate Variability (HRV), has been associated with Attention‐Deficit/ Hyperactivity Disorder (ADHD). This study investigated the dynamic vagal modulation of cardiac output in response to shifts in environmental demands in children and adolescents with ADHD, with and without a comorbid anxiety disorder. High‐frequency HRV (HF‐HRV) measures were obtained from 46 children and adolescents ranging from 6 to 17 (M = 9.38; SD = 2.31) years old, during three successive experimental conditions: a baseline recording followed by a sustained attention task, and a post‐task recovery period. Findings support the reliability of the d2 Test, a cancelation test of attention and concentration, to induce parasympathetic withdrawal and extend prior work on “vagal flexibility”. Further, these findings suggest a pattern of group differences in ANS functioning in children with ADHD, with and without a comorbid anxiety disorder. Only the ADHD without comorbid anxiety group showed a normative autonomic response to the cognitive challenge (reduced HF‐HRV). The participants did not display an adaptive process of restoration following the cognitive challenge; the HRV suppression was prolonged during post‐task recovery period, suggesting that ANS responded as if the cognitive stressor was still present. The current paper covers and discusses theoretical implications for the abnormalities in neurophysiological functioning and the different physiological responses in the two ADHD subtypes.
Rehabilitation of Mediterranean animal forests using gorgonians from fisheries by‐catch
Authors: Casoli Edoardo , Ventura Daniele , Mancini Gianluca , Cardone Sara , Farina Fulvia , Donnini Lorenzo , Pace Daniela Silvia , Shaul Richard , Belluscio Andrea , Ardizzone Giandomenico
Published: May 2021

The assessment of effective and affordable restoration interventions is pivotal to developing new tools to mitigate habitat loss and enhance natural recovery. Gorgonians create important three‐dimensional habitats in the Mediterranean Sea providing several ecosystem services associated with coralligenous reefs. Transplantations of the octocorals Eunicella cavolini, Eunicella singularis, and Paramuricea clavata were carried out at the site impacted by the wreck of the Costa Concordia in 2012. A total of 135 by‐caught gorgonians, caught in the gears of local artisanal fishermen or found lying on the seabed by SCUBA divers, were transplanted on impacted coralligenous reefs between 20 and 35 m depth and monitored for 2.5 years. A high survival rate (82.1%) was recorded, with main losses attributable to the detachment of the organisms from the substrate rather than death of the colonies. Eunicella cavolini transplanted colonies and natural colonies used as controls were monitored and showed similar, and seasonally influenced, growth and healing rates. Epibiosis and necrosis events were reported in both transplanted and natural colonies during summer, highlighting the sensitivity of the species to thermal stress. The present study emphasizes the importance of a management framework as a stepping‐stone to achieve effective restoration outcomes, including the removal of pressures that caused changes in natural communities and the participation of local stakeholders. The effectiveness of the methods and procedures proposed in this work allowed the restoration activities to continue at a larger scale during summer and autumn 2020.
GIS‐based groundwater quality assessment using GQIs and fuzzy‐logic approach
Authors: Chaudhry Akshay Kumar , Sachdeva Payal
Published: May 2021

This study proposes the evaluation of GIS‐based groundwater quality index (GQI) and spatial variability with a hybrid system that combines Fuzzy Logic with GIS‐based GQI. A case study in the semi‐arid area of Punjab, namely Rupnagar, illustrates the proposed hybrid outline. Two GIS‐based GQI models GQI‐10 (using ten water quality parameters (WQPs)) and GQI‐6 (using six “apprehensive/crucial” WQPs), as well as hybrid Fuzzy Logic GIS‐based GQI (FGQI) (using six crucial WQPs) models, were developed using trapezoidal membership functions and rule sets based on expert's knowledge. Performance comparison of GQI models showed that the FGQI model predicts improved groundwater quality than the GQI‐10 and GQI‐6. FGQI model variance, RMSE, and R2 values are 84.25, 6.49, 0.89, respectively. Results have shown that the developed FGQI model is successful and GQI modelling suggests the use of northern and central groundwater without treatment to be unsafe for drinking purposes.
Regulation of cerebral blood flow by arterial PCO2 independent of metabolic acidosis at 5050 m
Authors: Caldwell Hannah G. , Smith Kurt J. , Lewis Nia C.S. , Hoiland Ryan L. , Willie Christopher K. , Lucas Samuel J.E. , Stembridge Michael , Burgess Keith R. , MacLeod David B. , Ainslie Philip N.
Published: May 2021

Key points

We investigated the influence of arterial PCO2 (PaCO2) with and without experimentally altered pH on cerebral blood flow (CBF) regulation at sea level and with acclimatization to 5050 m.

At sea level and high altitude, we assessed stepwise alterations in PaCO2 following metabolic acidosis (via 2 days of oral acetazolamide; ACZ) with and without acute restoration of pH (via intravenous sodium bicarbonate; ACZ+HCO3−).

Total resting CBF was unchanged between trials at each altitude even though arterial pH and [HCO3−] (i.e. buffering capacity) were effectively altered.

The cerebrovascular responses to changes in arterial [H+]/pH were consistent with the altered relationship between PaCO2 and [H+]/pH following ACZ at high altitude (i.e. leftward x‐intercept shifts).

Absolute cerebral blood velocity (CBV) and the sensitivity of CBV to PaCO2 was unchanged between trials at high altitude, indicating that CBF is acutely regulated by PaCO2 rather than arterial pH.

Alterations in acid‐base balance with progressive acclimatization to high altitude have been well‐established. However, how respiratory alkalosis and the resultant metabolic compensation interact to regulate cerebral blood flow (CBF) is uncertain. We addressed this via three separate experimental trials at sea level and following partial acclimatization (14 to 20 days) at 5050 m; involving: (1) resting acid‐base balance (control); (2) following metabolic acidosis via 2 days of oral acetazolamide at 250 mg every 8 h (ACZ; pH: Δ ‐0.07 ± 0.04 and base excess: Δ ‐5.7 ± 1.9 mEq⋅l–1, trial effects: P < 0.001 and P < 0.001, respectively); and (3) after acute normalization of arterial acidosis via intravenous sodium bicarbonate (ACZ + HCO3−; pH: Δ ‐0.01 ± 0.04 and base excess: Δ ‐1.5 ± 2.1 mEq⋅l–1, trial effects: P = 1.000 and P = 0.052, respectively). Within each trial, we utilized transcranial Doppler ultrasound to assess the cerebral blood velocity (CBV) response to stepwise alterations in arterial PCO2 (PaCO2), i.e. cerebrovascular CO2 reactivity. Resting CBF (via Duplex ultrasound) was unaltered between trials within each altitude, indicating that respiratory compensation (i.e. Δ ‐3.4 ± 2.3 mmHg PaCO2, trial effect: P < 0.001) was sufficient to offset any elevations in CBF induced via the ACZ‐mediated metabolic acidosis. Between trials at high altitude, we observed consistent leftward shifts in both the PaCO2‐pH and CBV‐pH responses across the CO2 reactivity tests with experimentally reduced arterial pH via ACZ. When indexed against PaCO2 – rather than pH – the absolute CBV and sensitivity of CBV‐PaCO2 was unchanged between trials at high altitude. Taken together, following acclimatization, CO2‐mediated changes in cerebrovascular tone rather than arterial [H+]/pH is integral to CBF regulation at high altitude.