bluuebunny/crossref_metadata_2025 huggingface dataset:
Abdominal lymph node metastasis by lymphatic spread through the thoracic duct in patients with non‐small‐cell lung cancer
Authors: Ryu Wookyung , Lee Myoung Kyu , Park Mi Hwa , Hyun In Young , Lee Minkyung , No Eun‐Ji , Yong Seok Joong , Kim Jung Soo , Lim Jun Hyeok , Ryu Jeong‐Seon
Published: May 2021

Background

Abdominal lymph node metastasis (ALNM) is common in patients with metastatic non‐small‐cell lung cancer (NSCLC). However, its mechanism of spread remains to be elucidated. We investigated whether thoracic duct has the role as a pathway for ALNM in NSCLC using clinical data.

Methods

We classified ALNM into subgroups by their location and evaluated its prevalence and association with clinical characteristics in 892 patients with metastatic NSCLC. The abdominal lymph nodes were classified into direct or indirect groups depending on whether they drain directly into the trunk (intestinal trunk or lumbar trunks) connected to the cisterna chyli.

Results

One hundred‐five patients (11.8%) had ALNM. The paraaortic lymph node was most commonly involved, followed by the aortocaval, left gastric, paracaval, and celiac lymph nodes. After grouping the patients by location of ALNM, 56 patients (53.3%) with ALNM were in the “direct only” group, only seven patients (6.7%) were in the “indirect only” group, and 42 patients (40.0%) were in “both” groups. In patients whose intrathoracic lesions were limited to the right thorax, there was a significantly lower prevalence of ALNM (3.4% vs. 14.3%, p < 0.001). On multivariate logistic regression analysis of clinical variables, higher N category was associated with increased risk of ALNM.

Conclusions

This study suggests that the thoracic duct is one of the potential routes of lymphatic spread to the abdominal lymph nodes. Clinicians should assess for the presence of ALNM during staging work‐up and follow‐up for NSCLC patients with intrathoracic lesion in left thorax and with high N category.
Improving population estimates of difficult‐to‐observe species: A dung decay model for forest elephants with remotely sensed imagery
Authors: Meier A. C. , Shirley M. H. , Beirne C. , Breuer T. , Lewis M. , Masseloux J. , Jasperse‐Sjolander L. , Todd A. , Poulsen J. R.
Published: May 2021

Accurate and ecologically relevant wildlife population estimates are critical for species management. One of the most common survey methods for forest mammals – line transects for animal sign with distance sampling – has assumptions regarding conversion factors that, if violated, can induce substantial bias in abundance estimates. Specifically, for sign (e.g. nests, dung) surveys, a single number representing total time for decay is used as a multiplier to convert estimated sign density into animal density. This multiplier is likely inaccurate if not derived from a study reflecting the spatiotemporal variation in decay times. Using dung decay observations from three protected areas in Gabon, and a previous study in Nouabalé‐Ndoki National Park (Congo), we developed Weibull survival models to adaptively predict forest elephant (Loxodonta cyclotis) dung decay based on environmental variables from field collected and remotely sensed data. Seasonal decay models based on remotely sensed covariates explained 86% of the variation for the wet season and 79% for the dry season. These models included canopy cover, cloud cover, humidity, vegetation complexity and slope as factors influencing dung decay. With these models, we assessed sensitivity of elephant density estimates to spatiotemporal environmental heterogeneity, showing that our methods work best for large‐scale studies >50 km2. We simulated decay studies with and without these variables in four Gabonese national parks and reanalyzed two previous surveys of elephants in Minkébé National Park, Gabon. Disregarding spatial and temporal variation in decay rate biased population estimates up to 1.6 and 6.9 times. Our reassessment of surveys in Minkébé National Park showed an expected loss of 78% of forest elephants over ten years, but the elephant abundance was 222% higher than previously estimated. Our models incorporate field or remotely sensed variables to provide an ecological context essential for accurate population estimates while reducing need for expensive decay field studies.
Latest Permian insects from Wapadsberg Pass, southern Karoo Basin, South Africa
Authors: Pretorius Abraham I , Labandeira Conrad C , Nel André , Prevec Rose
Published: May 2021

The Permian–Triassic global crisis was the only event to have a dramatic impact on insect diversity, with Palaeozoic insect clades disappearing and accompanied by the accelerated rise of modern lineages. To date, most Permian palaeoentomological work has focused on the upper Permian deposits of the Normandien Formation (Beaufort Group), KwaZulu–Natal Province. This paper describes the regional insect fauna preserved close to the Permian–Triassic boundary at Wapadsberg Pass, southern Karoo Basin of South Africa, which provides a rare glimpse into insect life immediately before this global crisis. Here, we describe six insect species from six families within five orders from the two Wapadsberg Pass localities. Mioloptera stuckenbergi (Grylloblattodea) and Permocicada sp. (Hemiptera) were recorded previously from the Lopingian KwaZulu–Natal Province. In addition, we detail the first potential occurrence of South African Permian Tettigoniida (Orthoptera: Tettigonioidea & Hagloidea) and Anthracoptilidae (Paoliida). An Auchenorrhynchan (Hemiptera) nymph and an undetermined insect (order uncertain) also are described.
Dermoscopic features of acute cutaneous lupus erythematosus: A retrospective analysis from a tertiary care centre of East India
Authors: Behera Biswanath , Palit Aparna , Sethy Madhusmita , Nayak Ashish Kumar , Dash Siddharth , Ayyanar Pavithra
Published: May 2021

Background

The cutaneous features of acute cutaneous lupus erythematosus (ACLE) can be confused with other dermatoses. The dermoscopic features of ACLE have rarely been reported.

Aims

We aimed to study the dermoscopic features of ACLE, malar rash, and generalized ACLE.

Materials and Methods

The dermoscopic features of all biopsy and direct immunofluorescence confirmed ACLE cases were analysed retrospectively between May 2019 and May 2020.

Results

A total of 21 patients with skin phototypes III, IV, or V were included in the analysis. A pinkish‐white to reddish‐white homogenous area (94.1%), brown dots, globules and peppering (76.4%), and keratotic follicular plugging (64.7%) were the common dermoscopic features observed in the case of generalized ACLE. Similarly, in the case of malar rash, a pinkish‐white to reddish‐white homogenous area (77.8%) was the most common dermoscopic feature, followed by keratotic follicular plugging (66.7%), scales (44.5%), and brown dots, globules, and peppering (44.5%). In both variants, vascular structures were dominated by linear vessels with or without branching.

Conclusions

A multicomponent pattern comprising white scales, homogenous pinkish‐white to the reddish‐white area, brown dots/globules/peppering, keratotic follicular plugging, and linear vessels with or without branching were the common dermoscopic features observed in our study and may indicate the diagnosis of both localized and generalized ACLE. In addition, a paucity of dotted vessels may serve as an additional clue.
Update on fungal keratitis in France: a case–control study
Authors: Olivier Roxane , Knoeri Juliette , Leveziel Loïc , Negrier Pierre , Georgeon Cristina , Kobal Alfred , Bouheraoua Nacim , Baudouin Christophe , Nordmann Jean‐Philippe , Brignole‐Baudouin Françoise , Merabet Lilia , Borderie Vincent
Published: May 2021

Purpose

To report an epidemiological update of documented fungal keratitis (FK) in a French tertiary ophthalmological centre from 2014 to 2018 in comparison with a previous period from 1993 to 2008.

Methods

Sixty‐two consecutive FK documented by microbiological corneal scrapings were compared with the 64 FK of the previous study. Amphotericin B and voriconazole eye drops were administered hourly. Population characteristics, clinical findings, aetiological organisms and treatments were analysed.

Results

The most frequently identified fungi were Fusarium (61%), Aspergillus (6.5%) and Candida (5%). Thirty out of 44 cases examined with in vivo confocal microscopy (IVCM) presented filaments. Ten required conventional cross‐linking, 9 therapeutic penetrating keratoplasty, and 2 enucleation. Risk factors significantly associated with the absence of response to medical treatment were patient age (p = 0.01), presence of a deep stromal infiltrate at presentation (p = 0.04) and high numbers of filaments in IVCM images (p = 0.01). The two populations were comparable in age, but not in sex ratio males/females (18/44 versus 37/26 in the previous study; p = 0.001). The frequency of contact lens‐associated infection increased from 35.5% to 71% (p = 0.0001) between the two periods. Since then, filamentous FK increased from 69% (44/64) to 95% (59/62) (p = 0.0001). A history of keratoplasty was less frequently reported during the last period (3.2% (2/62) versus 17% (11/64) of cases (p = 0.01)). A clear decrease in the frequency of therapeutic keratoplasty was noted from 39% (25/64) to 14% (9/62) (p = 0.02).

Conclusion

The frequency of filamentous keratomycosis is currently increasing. Elderly patients and the presence of numerous filaments in IVCM are associated with poor clinical outcomes.
Barriers to antibody therapy in solid tumors, and their solutions
Authors: Matsumura Yasuhiro
Published: May 2021

Antibody drugs have become the mainstream of cancer treatment due to advances in cancer biology and Ab engineering. However, several barriers to Ab therapy have also been identified. These include various mechanisms for Ab drug resistance, such as heterogeneity of antigen expression in tumor cells and reduction in antitumor immunity due to expression diversity, polymorphism of Fc receptors (FcR) in effector cells, and reduced function of effector cells. Countermeasures to each resistance mechanism are being investigated. This review focuses on barriers that impede the delivery of Ab drugs due to features of the solid tumor microenvironment. Unlike hematological malignancies, in which the target tumor cells are in blood vessels, clinical solid tumors contain cancer stroma, which interferes with the delivery of Ab drugs. In addition, the cancer mass itself interferes with the penetration of Ab drugs. In this article, I will consider the etiology of cancer stroma and propose a new Ab drug development strategy for solid cancer treatment centering on cancer stromal targeting (CAST) therapy using anti‐insoluble fibrin Ab‐drug conjugate (ADC), which can overcome the cancer stroma barrier. The recent success of ADCs, chimeric antigen receptor T cells (CAR‐Ts), and Bi‐specific Abs is changing the category of Ab drugs from molecular‐targeted drugs based on growth signal inhibition to cancer‐specific targeted therapies. Therefore, at the end of this review, I argue that it is time to reorient the concept of Ab drug development.
Unraveling pathologies underlying chromosomal instability in cancers
Authors: Jo Minji , Kusano Yoshiharu , Hirota Toru
Published: May 2021

Aneuploidy is a widespread feature of malignant tumors that arises through persistent chromosome mis‐segregation in mitosis associated with a pathological condition called chromosomal instability, or CIN. Since CIN is known to have a causal relationship with poor prognosis accompanying by multi‐drug resistance, tumor relapse, and metastasis, many research groups have endeavored to understand the mechanisms underlying CIN. In this review, we overview possible etiologies of CIN. The key processes to achieve faithful chromosome segregation include the regulation of sister chromatid cohesion, kinetochore‐microtubule attachment, bipolar spindle formation, spindle‐assembly checkpoint, and the activity of separase. Aberrant chromosome structures during DNA replication might also be a potential cause of CIN. Defective regulation in these processes can lead to chromosome mis‐segregation, manifested by lagging chromosomes, and DNA bridges in anaphase, leading to gross chromosome rearrangements. Investigation into the molecular etiologies of CIN should allow us to explore novel strategies to intervene in CIN to control cancers.
Preschool‐Aged Children Jointly Consider Others’ Emotional Expressions and Prior Knowledge to Decide When to Explore
Authors: Wu Yang , Gweon Hyowon
Published: May 2021

Emotional expressions are abundant in children’s lives. What role do they play in children’s causal inference and exploration? This study investigates whether preschool‐aged children use others’ emotional expressions to infer the presence of unknown causal functions and guide their exploration accordingly. Children (age: 3.0–4.9; N = 112, the United States) learned about one salient causal function of a novel toy and then saw an adult play with it. Children explored the toy more when the adult expressed surprise than when she expressed happiness (Experiment 1), but only when the adult already knew about the toy’s salient function (Experiment 2). These results suggest that children consider others’ knowledge and selectively interpret others’ surprise as vicarious prediction error to guide their own exploration.
Role of maternal tryptophan metabolism in allergic diseases in the offspring
Authors: Lau Hui Xing , El‐Heis Sarah , Yap Qai Ven , Chan Yiong Huak , Tan Cheryl Pei Ting , Karnani Neerja , Tan Karen Mei Ling , Tham Elizabeth Huiwen , Goh Anne Eng Neo , Teoh Oon Hoe , Tan Kok Hian , Eriksson Johan Gunnar , Chong Yap Seng , Chong Mary Foong‐Fong , Van Bever Hugo , Lee Bee Wah , Shek Lynette P. , Godfrey Keith M. , Loo Evelyn Xiu Ling
Published: May 2021

Background

Nicotinamide (vitamin B3) is a metabolite of tryptophan and dietary precursor of enzymes involved in many regulatory processes, which may influence fetal immune development.

Objective

We examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated with the risk of development of infant eczema, wheeze, rhinitis or allergic sensitization.

Methods

In the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, we analysed the associations between maternal plasma levels of nicotinamide, tryptophan and tryptophan metabolites at 26–28 weeks of gestation and allergic outcomes collected through interviewer‐administered questionnaires at multiple time‐points and skin prick testing to egg, milk, peanut and mites at age 18 months. Multivariate analysis was undertaken adjusting for all metabolites measured and separately adjusting for relevant demographic and environmental exposures. Analyses were also adjusted for multiple comparisons using the false discovery method.

Results

Tryptophan metabolites were evaluated in 976/1247 (78%) women enrolled in GUSTO. In multivariate analysis including all metabolites, maternal plasma 3‐hydrokynurenine was associated with increased allergic sensitization at 18 months (AdjRR 2.6, 95% CI 1.3–5.2 for highest quartile) but the association with nicotinamide was not significant (AdjRR 1.8, 95% CI 0.9–3.6). In analysis adjusting for other exposures, both 3‐hydrokynurenine and nicotinamide were associated with increased allergic sensitization (AdjRR 2.0, 95% CI 1.1–3.6 for both metabolites). High maternal plasma nicotinamide was associated with increased infant eczema diagnosis by 6 and 12 months, which was not significant when adjusting for all metabolites measured, but was significant when adjusting for relevant environmental and demographic exposures. Other metabolites measured were not associated with allergic sensitization or eczema, and maternal tryptophan metabolites were not associated with offspring rhinitis and wheeze.

Conclusions and Clinical Relevance

Maternal tryptophan metabolism during pregnancy may influence the development of allergic sensitization and eczema in infants.
Biology of sinus floor augmentation with an autograft versus a bone graft substitute in a preclinical in vivo experimental model
Authors: Coyac Benjamin R. , Wu Meagan , Bahat Daniel J. , Wolf Benjamin J. , Helms Jill A.
Published: May 2021

Objectives

Compared to autografts, bone graft substitutes are slower to consolidate. If we understood why, this might open strategies to accelerate new bone formation and thus shorten the time to implant placement. In this study, we aimed at comparing autologous bone graft with a bovine bone graft substitute in a preclinical sinus lift model.

Materials and Methods

The mouse posterior paranasal sinus served as a recipient site for grafting. Autograft from the oral cavity was compared against bone graft substitute using molecular, cellular, and histological analyses conducted on post‐grafting days (PSD) 0, 9, 18, and 120.

Results

Either autografts or bone graft substitutes were positioned on the sinus floor and remained in situ throughout the study. At the time of grafting and until day 9, bone graft substitutes were devoid of cells and alkaline phosphatase (ALP) activity while autografts were comprised of viable cells and showed strong ALP (mineralization) activity. Consequently, new bone formed faster in autografts compared to bone graft substitutes (140.21 ± 41.21 µm vs. 41.70 ± 10.09 µm, respectively, PSD9,p = .0143). By PSD18, osteogenesis was evident in autografted and xenografted sites. Osteoclasts identified by tartrate resistant acid phosphatase attached to, but did not resorb the bone graft substitute matrix. Autograft matrix, however, underwent extensive resorption. Transgenic mice revealed that Wnt‐responsive osteoprogenitor cells originated primarily from the internal periosteum of the maxillary bone, and not from the Schneiderian membrane.

Conclusion

Autografts produce new bone sooner, but bovine bone graft substitutes eventually consolidate and then resist resorption. Enhancing osteoprogenitor cell recruitment to a bone graft substitute constitutes a viable strategy for accelerating bone formation in a sinus lift procedure.
Training, supervision and performance of Community Health Workers in the delivery of ear and hearing care to 321 community members in rural Uganda
Authors: O’Donovan James , Nakku Doreen , Nyanzi Daniel , Nakasagga Esther , Hamala Rebecca , Namanda Allan S. , Kabali Kenneth , Winters Niall , Chadha Shelly , Bhutta Mahmood F.
Published: May 2021

Objectives

Community Health Workers are one way to address the shortage of ear and hearing care specialists in low‐resource settings. However, there are few reports evaluating training and service delivery by Community Health Workers.

Design, setting and participants

We trained 13 Community Health Workers in primary ear and hearing care in Mukono District, Uganda. Community Health Workers attended a two‐day training workshop and received remote supervision thereafter during service delivery in the community. An ear camp was held at the local health centre every two months, where a local ENT specialist could assess referred cases.

Main outcome measures

Clinical and diagnostic skills and decision‐making were assessed using an Objective Structured Clinical Examination, with scores recorded at baseline and six months. Service delivery was evaluated by analysing the following: (i) number of individuals evaluated; (ii) treatments delivered; (iii) cases referred for specialist opinion; (iv) proportion of appropriately referred cases; and (v) agreement between Community Health Worker and specialist diagnosis.

Results

Observed Structured Clinical Examination scores were high and stable for six months. 312 individuals were screened in the community by the Community Health Workers, with 298 classified as having an abnormality. Care was delivered in the community to 167 of these, and the remaining 131 referred to the ear camp. Diagnostic agreement was 39%, but 98% of referrals were deemed “appropriate” by the ENT specialist. 27 individuals self‐presented to the ear camp without prior assessment by a Community Health Worker, and 97% of these were deemed appropriate.

Conclusion

Trained Community Health Workers can play an important role in delivering ear and hearing services. Future work should look to explore this model in other contexts and/or compare it to other models of service delivery.
Sequential assessment of bowel function and anorectal physiology after anterior resection for cancer: a prospective cohort study
Authors: Pilkington Sophie A. , Bhome Rahul , Gilbert Sally , Harris Scott , Richardson Carl , Dudding Thomas C. , Knight John S. , King Andrew T. , Mirnezami Alex H. , Beck Nicholas E. , Nichols Paul H. , Nugent Karen P.
Published: May 2021

Aim

The aim of this study was to investigate changes in bowel function and anorectal physiology (ARP) after anterior resection for colorectal cancer.

Method

Patients were recruited from November 2006 to September 2008. Cleveland Clinic Incontinence (CCI) scores and stool frequency were determined by patient questionnaires before surgery (t0) and at three (t3), six (t6), nine (t9) and 12 (t12) months after restoration of intestinal continuity. ARP measurements were recorded at T0, T3 and T12. Endoanal ultrasound was performed at T0 and T12.

Results

Eighty‐nine patients were included. CCI score increased postoperatively then normalized, whereas stool frequency did not change. Patients who had neoadjuvant radiotherapy or a lower anastomosis had increased incontinence and stool frequency in the postoperative period, whereas those with defunctioning stomas or open surgery had increased stool frequency alone. Maximum resting pressure, volume at first urge and maximum rectal tolerance were reduced throughout the postoperative period. Radiotherapy, lower anastomosis and defunctioning stoma (but not operative approach) altered manometric parameters postoperatively. Maximum rectal tolerance correlated with incontinence and first urge with stool frequency. The length of the anterior internal anal sphincter decreased postoperatively.

Conclusions

Incontinence recovers in the first year after anterior resection. Radiotherapy, lower anastomosis, defunctioning stoma and open surgery have a negative influence on bowel function. ARP may be useful if bowel dysfunction persists beyond 12 months.
Quantitative cytomorphological comparison of SurePath and ThinPrep liquid‐based cytology using high‐grade urothelial carcinoma cells
Authors: Okuda Chihiro , Kyotake Aiko , Nakamura Akihiro , Itoh Tomoo , Kamoshida Shingo , Ohsaki Hiroyuki
Published: May 2021

Objective

In The Paris System for Reporting Urinary Cytology (TPS), the important cytomorphological features for diagnosing high‐grade urothelial carcinoma (HGUC) are a nuclear‐to‐cytoplasmic (N:C) ratio exceeding 0.7, hyperchromasia, coarse chromatin, and irregular nuclear borders. However, quantitative cytomorphological assessments of HGUC cells using SurePath slides are rare. Therefore, we evaluated HGUC cells on SurePath slides quantitatively using a digital image analysis system and compared these data with ThinPrep data.

Methods

The same urine samples were divided into two aliquots and used to prepare SurePath and ThinPrep slides. We used ImageJ to measure the N:C ratio, hyperchromasia, and irregular nuclear borders for HGUC cells on SurePath and ThinPrep slides.

Results

The total number of analysed HGUC cells on SurePath slides was 981, versus 889 on ThinPrep slides. Hyperchromasia and irregular nuclear borders were significantly more severe on SurePath than on ThinPrep slides. Conversely, the N:C ratio did not differ between the methods. Additionally, HGUC cells with N:C ratios exceeding 0.7 were present on almost all slides for both methods.

Conclusions

Our data indicated the reasonableness of using the N:C ratio as the major criterion for TPS on both SurePath and ThinPrep slides, and an N:C ratio cut‐off of 0.7 as suitable for identifying HGUC cells. However, the severity of hyperchromasia and irregular nuclear borders differed between the processing methods.
Atypical presentations of erythema nodosum leprosum: Diagnostic and therapeutic aspects
Authors: Alakad Rania , Nofal Ahmad , Assaf Magda
Published: May 2021

Classic erythema nodosum leprosum (ENL) is characterized clinically by abrupt eruption of tender erythematous nodules, papules and plaques. Variable atypical patterns have been described, for example pustular, bullous, ulcerative, necrotic and Sweet’s syndrome‐like ENL. We aim to review previously reported cases of atypical ENL addressing the diagnostic and therapeutic aspects of these uncommon presentations. A search of medical literature for all cases of atypical ENL was conducted in the PubMed database till 2020. Data of patients with atypical ENL were collected and analyzed to describe the epidemiological, clinico‐histological and therapeutic features. The major five clinically described presentations of atypical ENL include vesiculo‐bullous lesions (46 % of patients), ulcero‐necrotic lesions (41 %), erythema multiforme‐like lesions (28 %), Sweet’s syndrome‐like lesions (11 %) and pustules (9 %). The skin lesions were accompanied by fever and constitutional symptoms in all patients. Oral steroids and thalidomide were the main lines of therapy in most of the reported patients. Dermatologists and pathologists should keep in mind the clinical variability of ENL to avoid misdiagnosis and delayed management. Early recognition can help control disease progression and save the patients from further complications.
Prediabetes is associated with proteinuria development but not with glomerular filtration rate decline: A longitudinal observational study
Authors: Furukawa Mariko , Onoue Takeshi , Kato Kiminori , Wada Takashi , Shinohara Yukito , Kinoshita Fumie , Goto Motomitsu , Arima Hiroshi , Tsushita Kazuyo
Published: May 2021

Aims

Diabetes is recognized as the leading cause of chronic kidney disease (CKD); however, the association of prediabetes with CKD remains unclear, in particular, the independent effect of prediabetes on proteinuria or estimated glomerular filtration rate (eGFR) has not been evaluated. This study aimed to investigate the associations of prediabetes with the proteinuria development and with eGFR decline separately in the Japanese general population without CKD.

Methods

Participants who underwent health check‐ups in 2014 and had adequate data after 2 years were retrospectively analysed. A total of 405,487 participants without CKD (eGFR, ≥60 ml min−1 1.73 m−2, with negative or trace urinary protein) at baseline were categorized according to fasting plasma glucose as having diabetes (≥126 mg/dl [7.0 mmol/l]), prediabetes (100–125 mg/dl [5.6–6.9 mmol/l]) or normal glucose level (˂100 mg/dl [5.6 mmol/l]). Logistic regression analysis was used to analyse the effects of prediabetes (vs. normal glucose level) on the proteinuria development (urinary protein of ≥1+) and eGFR decline (˂60 ml min−1 1.73 m−2) after 2 years.

Results

After 2 years, 7037 participants (1.7%) developed proteinuria alone, 19,015 (4.7%) presented eGFR decline alone and 636 (0.2%) showed both proteinuria and eGFR decline. Compared to normal glucose level and adjusting for prognostic factors, prediabetes was independently associated with the proteinuria development (odds ratio [OR] 1.233; 95% confidence interval [CI] 1.170–1.301], whereas prediabetes was not associated with eGFR decline (OR 0.981; 95% CI 0.947–1.017).

Conclusions

Prediabetes is associated with the proteinuria development but not with eGFR decline in the general population.
Prevalence of multimorbidity and its impact on survival in people with motor neuron disease
Authors: Glasmacher Stella A. , Kearns Patrick K. A. , Larraz Juan , Stirland Lucy , Mehta Arpan R. , Newton Judith , Weir Christopher J. , Chandran Siddharthan , Pal Suvankar ,   CARE‐MND Consortium
Published: May 2021

Background and purpose

This study was undertaken to determine the prevalence of multimorbidity in people with motor neuron disease (MND) and to identify whether specific patterns of multimorbidity impact survival beyond age alone.

Methods

We performed a retrospective analysis of the Scottish national MND register from 1 January 2015 to 29 October 2019. People with amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy, or progressive bulbar palsy were included. We fitted latent class regression models incorporating comorbidities (class indicators), age, sex, and bulbar onset (covariates), and survival (distal outcome) with multimorbidity as a hypothesised latent variable. We also investigated the association between the Charlson Comorbidity Index and survival in Cox regression and compared its discrimination and calibration to age alone.

Results

A total of 937 people with MND were identified (median age = 67 years, 60.2% male); 64.8% (n = 515) had two or more comorbidities. We identified a subpopulation with high prevalence of cardiovascular disease, but when accounting for the relationship between age and individual comorbidities, there was no difference in survival. Both Charlson Comorbidity Index (hazard ratio [HR] per unit increase = 1.11, 95% confidence interval [CI] = 1.07–1.15, p < 0.0001) and age (HR per year increase = 1.04, 95% CI = 1.03–1.05, p < 0.0001) were significantly associated with survival, but discrimination was higher for age compared to Charlson Comorbidity Index (C‐index = 0.63 vs. 0.59).

Conclusions

Multimorbidity is common in MND, necessitating holistic interdisciplinary management, but age is the dominant predictor of prognosis in people with MND. Excluding people with MND and multimorbidity from trial participation may do little to homogenise the cohort in terms of survival potential and could harm generalisability.
A fixed structure learning automata‐based optimization algorithm for structure learning of Bayesian networks
Authors: Asghari Kayvan , Masdari Mohammad , Soleimanian Gharehchopogh Farhad , Saneifard Rahim
Published: May 2021

One of the useful knowledge representation tools, which can describe the joint probability distribution between some random variables with a graphical model and can be trained by a dataset, is the Bayesian network (BN). A BN is composed of a network structure and a conditional probability distribution table for each node. Discovering an optimal BN structure is an NP‐hard optimization problem that various meta‐heuristic algorithms are applied to solve this problem by researchers. The genetic algorithms, ant colony optimization, evolutionary programming, artificial bee colony, and bacterial foraging optimization are some of the meta‐heuristic methods to solve this problem using a dataset. Most of these methods are applying a scoring metric to generate the best network structure from a set of candidates. A Fixed Structure Learning Automata‐Based (FSLA‐B) algorithm is presented in this paper to solve the structure learning problem of BNs. There is a fixed structure learning automaton for each pair of vertices in the BN's graph structure in the proposed algorithm. The action of this automaton determines the presence and direction of an edge between the vertices. The proposed algorithm performs a guided search procedure using the FSLA and escapes from local optimums. Several datasets are utilised in this paper to evaluate the performance of the proposed algorithm. By performing various experiments, multiple meta‐heuristic algorithms are compared with the introduced new one. The obtained results represented that the proposed algorithm could produce competitive results and find the near‐optimal solution for the BN structure learning problem.
Hybrid intelligent framework for automated medical learning
Authors: Belhadi Asma , Djenouri Youcef , Diaz Vicente Garcia , Houssein Essam H. , Lin Jerry Chun‐Wei
Published: May 2021

This paper investigates the automated medical learning and proposes hybrid intelligent framework, called Hybrid Automated Medical Learning (HAML). The goal is the efficient combination of several intelligent components in order to automatically learn the medical data. Multi agents system is proposed by using distributed deep learning, and knowledge graph for learning medical data. The distributed deep learning is used for efficient learning of the different agents in the system, where the knowledge graph is used for dealing with heterogeneous medical data. To demonstrate the usefulness and accuracy of the HAML framework, intensive simulations on medical data were conducted. A wide range of experiments were conducted to verify the efficiency of the proposed system. Three case studies are discussed in this research, the first case study is related to process mining, and more precisely on the ability of HAML to detect relevant patterns from event medical data. The second case study is related to smart building, and the ability of HAML to recognize the different activities of the patients. The third one is related to medical image retrieval, and the ability of HAML to find the most relevant medical images according to the image query. The results show that the developed HAML achieves good performance compared to the most up‐to‐date medical learning models regarding both the computational and cost the quality of returned solutions.
Centennial relationships between ocean temperature and Atlantic puffin production reveal shifting decennial trends
Authors: Hansen Erpur S. , Sandvik Hanno , Erikstad Kjell Einar , Yoccoz Nigel G. , Anker‐Nilssen Tycho , Bader Jürgen , Descamps Sébastien , Hodges Kevin , Mesquita Michel d. S. , Reiertsen Tone K. , Varpe Øystein
Published: May 2021

The current warming of the oceans has been shown to have detrimental effects for a number of species. An understanding of the underlying mechanisms may be hampered by the non‐linearity and non‐stationarity of the relationships between temperature and demography, and by the insufficient length of available time series. Most demographic time series are too short to study the effects of climate on wildlife in the classical sense of meteorological patterns over at least 30 years. Here we present a harvest time series of Atlantic puffins (Fratercula arctica) that goes back as far as 1880. It originates in the world's largest puffin colony, in southwest Iceland, which has recently experienced a strong decline. By estimating an annual chick production index for 128 years, we found prolonged periods of strong correlations between local sea surface temperature (SST) and chick production. The sign of decennial correlations switches three times during this period, where the phases of strong negative correlations between puffin productivity and SST correspond to the early 20th century Arctic warming period and to the most recent decades. Most of the variation (72%) in chick production is explained by a model in which productivity peaks at an SST of 7.1°C, clearly rejecting the assumption of a linear relationship. There is also evidence supporting non‐stationarity: The SST at which puffins production peaked has increased by 0.24°C during the 20th century, although the increase in average SST during the same period has been more than three times faster. The best supported models indicate that the population's decline is at least partially caused by the increasing SST around Iceland.
Functional biogeography of Neotropical moist forests: Trait–climate relationships and assembly patterns of tree communities
Authors: Pinho Bruno X. , Tabarelli Marcelo , ter Braak Cajo J. F. , Wright S. Joseph , Arroyo‐Rodríguez Víctor , Benchimol Maíra , Engelbrecht Bettina M. J. , Pierce Simon , Hietz Peter , Santos Bráulio A. , Peres Carlos A. , Müller Sandra C. , Wright Ian J. , Bongers Frans , Lohbeck Madelon , Niinemets Ülo , Slot Martijn , Jansen Steven , Jamelli Davi , de Lima Renato A. F. , Swenson Nathan , Condit Richard , Barlow Jos , Slik Ferry , Hernández‐Ruedas Manuel A. , Mendes Gabriel , Martínez‐Ramos Miguel , Pitman Nigel , Kraft Nathan , Garwood Nancy , Guevara Andino Juan Ernesto , Faria Deborah , Chacón‐Madrigal Eduardo , Mariano‐Neto Eduardo , Júnior Valdecir , Kattge Jens , Melo Felipe P. L.
Published: May 2021

Aim

Here we examine the functional profile of regional tree species pools across the latitudinal distribution of Neotropical moist forests, and test trait–climate relationships among local communities. We expected opportunistic strategies (acquisitive traits, small seeds) to be overrepresented in species pools further from the equator, but also in terms of abundance in local communities in currently wetter, warmer and more seasonal climates.

Location

Neotropics.

Time period

Recent.

Major taxa studied

Trees.

Methods

We obtained abundance data from 471 plots across nine Neotropical regions, including c. 100,000 trees of 3,417 species, in addition to six functional traits. We compared occurrence‐based trait distributions among regional species pools, and evaluated single trait–climate relationships across local communities using community abundance‐weighted means (CWMs). Multivariate trait–climate relationships were assessed by a double‐constrained correspondence analysis that tests both how CWMs relate to climate and how species distributions, parameterized by niche centroids in climate space, relate to their traits.

Results

Regional species pools were undistinguished in functional terms, but opportunistic strategies dominated local communities further from the equator, particularly in the Northern Hemisphere. Climate explained up to 57% of the variation in CWM traits, with increasing prevalence of lower‐statured, light‐wooded and softer‐leaved species bearing smaller seeds in more seasonal, wetter and warmer climates. Species distributions were significantly but weakly related to functional traits.

Main conclusions

Neotropical moist forest regions share similar sets of functional strategies, from which local assembly processes, driven by current climatic conditions, select for species with different functional strategies. We can thus expect functional responses to climate change driven by changes in relative abundances of species already present regionally. Particularly, equatorial forests holding the most conservative traits and large seeds are likely to experience the most severe changes if climate change triggers the proliferation of opportunistic tree species.
Exploring Biases in Atom Probe Tomography Compositional Analysis of Minerals
Authors: Cappelli Chiara , Smart Sandi , Stowell Harold , Pérez‐Huerta Alberto
Published: May 2021

Atom probe tomography (APT) is emerging as a key nanogeochemistry technique for diverse geoscience applications. Estimating stoichiometric mineral compositions is particularly challenging for features at nanoscale. APT provides reliable measurements for metallic systems but the reliability for oxides is problematic, notably due to oxygen deficit. Here, we use laser‐assisted APT to compare results for spinel and garnet crystals. APT compositional results were compared with those by electron microprobe to determine the possible APT analytical inaccuracy. Extensive data processing was accomplished, including correlation histograms, 2D ion distribution maps and 1D elements concentration profiles, to disclose the possible mechanisms leading to mineral stoichiometry biases. Multiple events and neutral molecules formation are probable the main processes responsible for atom deficit. In particular, the amount of the same isotope–same charge state ion pairs correlated with aluminium and oxygen deficits suggests that the co‐evaporation in a dead space–dead time window could lead to a significant decrease of detected ions. Also, molecular species dissociation and direct current evaporation could partially account for further atom loss. Overall, better APT compositional estimation was obtained for spinel, which has lesser variation in lattice sites and greater overall lattice symmetry, higher thermal conductivity and lower band gap compared with garnet.
Kali Age Crisis as Jaina‐Brahmana conflict: A contribution to Indian Feudalism debate
Authors: Rao Nagendra
Published: May 2021

This paper reviews and reinterprets the representation of the Kali Age Crisis as the reflection of feudalism, thus analyzing the feudalism debate. It substantiates the argument that the Kali Age Crisis did not represent feudalism. The apprehension of Brahmanas regarding the Kali Age did not emerge from political decentralization. It was the result of the competition from Jainism, particularly in south India. The Brahmanas were wary of the Jainas consuming a major share of the state patronage, thereby depriving the Brahmanas of the material resources, which they aimed to monopolize.
Short‐term scheduling with machine calibration
Authors: Xu Dehua , Xu Zhijun , Xu Limin , Yu Xianyu
Published: May 2021

In most of the past research on scheduling, it is conventional to model machine deterioration by decreasing production speed over time. However, as is observed, there is a fair number of scenarios in practice where deterioration has a little impact on machine speed but a great impact on production accuracy and a machine is unusable unless it has been calibrated recently. In this paper, we consider a single‐machine short‐term scheduling issue in distributed production systems where the engineer calibrates the machines in a round‐robin manner. The objective is to minimize total job completion time, which is a popular criterion indicating total holding or inventory cost. We consider two cases of the problem and show that one of them can be solved optimally by providing an extended shortest processing time first rule. As for the other case, which is intractable, we propose a polynomial‐time approximation scheme based on the extended rule and an exchange procedure. Computational experiments show that the proposed polynomial‐time approximation scheme is very promising even if limited number of exchangeable jobs is allowed.
Herd solutions from genetic evaluations can be used as a tool to rescale the expected expression of genetic potential in cattle
Authors: Kenny David , Sleator Roy D. , Murphy Craig P. , Evans Ross D. , Berry Donagh P.
Published: May 2021

The objective of this study was to determine whether response to selection for carcass weight (CW), conformation (CC) and fat (CF), and the association between heterosis and carcass performance varied by herd environment in cattle. Following edits, carcass information was available for 4,616,761 cattle, of which the majority were some crossbred combination of the following breeds: Angus, Aubrac, Belgian Blue, Blonde d’Aquitaine, Charolais, Hereford, Holstein‐Friesian, Jersey, Limousin, Saler, Shorthorn and Simmental. Herd environment was defined separately for each carcass trait using herd solutions outputted from carcass trait genetic evaluations. A total of 3,859 herds were stratified, for each trait, into one of five strata based on their corresponding percentile herd solution rank, with the response to selection and the effect of heterosis then estimated within each stratum. The response in CW and CC from selection on the respective estimated breeding values (EBV) increased between the lowest (0.71 kg and 0.89 CC score increase per unit increase in the respective EBV) and highest (0.99 kg and 1.25 CC score increase per unit increase in the respective EBV) corresponding herd stratum. The response in CF from selection on CF EBV, however, reduced between the lowest and highest CF herd stratum (respective increases of 0.93 and 0.83 CF scores per unit increase in CF EBV). In addition, the effect of a unit increase in heterosis coefficient on CW, CC and CF also varied by herd stratum. Furthermore, results (i.e. the area under relative operating characteristic curves) from the present study demonstrated that the response to selection and heterosis effects estimated for the different herd stratum can be used, along with EBVs and the herd solutions themselves, to improve the accuracy of phenotypic predictions. Results from the present study could help producers to make more informed breeding decisions that are bespoke to their herd.
Verapamil inhibits early acute liver failure through suppressing the NLRP3 inflammasome pathway
Authors: Han Mingying , Li Shouzhou , Li Lanrong
Published: May 2021

Acute liver failure (ALF) is a rare disease characterized by the sudden onset of serious hepatic injury, as manifested by a profound liver dysfunction and hepatic encephalopathy in patients without prior liver disease. In this paper, we aim to investigate whether verapamil, an antagonist of TXNIP, inhibits early ALF through suppressing the NLRP3 inflammasome pathway. Firstly, an ALF mouse model was induced by lipopolysaccharide (LPS)/D‐galactosamine (GalN) treatment. The optimal concentration of verapamil in treating early ALF mice was determined followed by investigation on its mechanism in LPS/GalN‐induced liver injury. Western blot analysis and co‐immunoprecipitation were performed to determine the activation of the TXNIP/NLRP3 inflammasome pathway. Subsequently, overexpression of NLRP3 in mouse liver was induced by transfection with AAV‐NRLP3 in vivo and in vitro to identity whether verapamil inhibited early ALF through suppressing the activation of NLRP3 inflammasome. We found that ALF was induced by LPS/GalN in mice but was alleviated by verapamil through a mechanism that correlated with suppression of the NLRP3 inflammasome pathway. Oxidative stress and inflammatory response were induced by intraperitoneal injection of LPS/GalN, but alleviated with injection of verapamil. Overexpression of NLRP3 via AAV in mouse liver in vivo and in vitro reduced the therapeutic effect of verapamil on LPS/GalN‐induced ALF. Taken together, the TXNIP antagonist verapamil could inhibit activation of the NLRP3 inflammasome, inflammatory responses and oxidative stress to alleviate LPS/GalN‐induced ALF.
Organoid models of the tumor microenvironment and their applications
Authors: Xia Tao , Du Wen‐Lin , Chen Xiao‐Yi , Zhang You‐Ni
Published: May 2021

A small percentage of data obtained from animal/2D culture models can be translated to humans. Therefore, there is a need to using native tumour microenvironment mimicking models to improve preclinical screening and reduce this attrition rate. For this purpose, currently, the utilization of organoids is expanding. Tumour organoids can recapitulate tumour microenvironment that is including cancer cells and non‐neoplastic host components. Indeed, tumour organoids, both phenotypically and genetically, resemble the tumour tissue that originated from it. The unique properties of the tumour microenvironment can significantly affect drug response and cancer progression. In this review, we will discuss about various organoid culture strategies for modelling the tumour immune microenvironment, their applications and advantages in cancer research such as testing cancer immunotherapeutics, developing novel approaches for personalized medicine, testing drug toxicity, drug screening, study cancer initiation and progression, and we will also review the limitations of organoid culture systems.