bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of the automated column agglutination technique for titration of anti‐A/B antibodies in ABO‐incompatible living kidney transplantation
Authors: Matsuura Hideaki , Sugiura Yukari , Matsuno Takahiro , Tomiya Yume , Shiraki Mari , Kato Chiaki , Ishihara Keiko , Fukami Harue , Niwa Reiko , Hayashi Megumi , Matsushita Tadashi , Kato Hidefumi , Watarai Yoshihiko , Ito Taihei , Kenmochi Takashi , Fujii Sumie , Miura Yasuo
Published: November 2021

Introduction

Quantitative measurement of anti‐A/‐B antibody titers is important during ABO‐incompatible living kidney transplantation (ABOi‐LKT).

Methods

We conducted a multi‐institutional study to measure the antibody titers using the automated column agglutination technique (auto‐CAT) and tube test (TT) method in ABOi‐LKT recipients. Statistical analysis was performed to evaluate the two methods.

Results

We examined 111 samples from 35 ABOi‐LKT recipients at four institutions. The correlation coefficient of the two methods was >0.9; the concordance rate and clinically acceptable concordance rate for the IgG titers were 60.4% and 88.3%, respectively. Perioperative status did not influence the statistical significance. Parallel changes were observed in the IgG antibody titers measured using the auto‐CAT or TT technique by desensitizing therapy in time‐course monitoring.

Conclusion

Auto‐CAT is comparable with the TT technique and is feasible for IgG anti‐A/B antibody titration in ABOi‐LKT recipients.
Efficacy and safety of an anti‐CD20 monoclonal antibody, rituximab, for lupus nephritis: A meta‐analysis
Authors: Teng Siyuan , Tian Yu , Luo Nan , Zheng Qiang , Shao Mingfang , Li Lei
Published: November 2021

Background

The efficacy and safety of rituximab (RTX) for lupus nephritis are still a controversial issue.

Methods

We systematically searched MEDLINE, EMBASE, and the Cochrane Library databases for all clinical controlled studies.

Results

Six studies with 588 patients were included in our meta‐analysis. RTX increased total renal remission rates (TR, odds ratio [OR] 2.16, 95% CI 1.31 to 3.55, P = .003) and complete renal remission rate (CR, OR 2.42, 95% CI 1.18 to 4.94, P = .02) compared with the control group. Subgroup analyses showed that rituximab was more effective at increasing the rate of TR and CR for lupus nephritis patients compared with mycophenolate mofetil (TR, OR 4.6, 95% CI 1.29 to 16.47, P = .02; CR, OR 2.56, 95% CI 1.19 to 5.47, P = .02) and cyclophosphamide (TR, OR 2.89, 95% CI 1.31 to 6.40, P = .009; CR, OR 2.75, 95% CI 1.19 to 6.4, P = .02). Rituximab also had advantage in reducing Systemic Lupus Erythematosus Disease Activity Index score (–2.49, 95% CI –3.77 to –1.22, P = .0001). There were no significant differences between the RTX group and control group on the change of proteinuria (–0.36 g/d, 95% CI –0.71 to –0.00 g/d, P = .05) and serum creatinine (0.13 mg/dL, 95% CI –0.15 to 0.42 mg/dL, P = .36). RTX treatment did not increase the risk of adverse events compared to the control group.

Conclusions

This study provides clear beneficial effects of RTX in patients with lupus nephritis. In addition, RTX therapy did not increase the risk of adverse events compared to the control group.
Utility of mass spectrometry and artificial intelligence for differentiating primary lung adenocarcinoma and colorectal metastatic pulmonary tumor
Authors: Shigeeda Wataru , Yosihimura Ryuichi , Fujita Yuji , Saiki Hidekazu , Deguchi Hiroyuki , Tomoyasu Makoto , Kudo Satoshi , Kaneko Yuka , Kanno Hironaga , Inoue Yoshihiro , Saito Hajime
Published: November 2021

Background

Rapid intraoperative diagnosis for unconfirmed pulmonary tumor is extremely important for determining the optimal surgical procedure (lobectomy or sublobar resection). Attempts to diagnose malignant tumors using mass spectrometry (MS) have recently been described. This study evaluated the usefulness of MS and artificial intelligence (AI) for differentiating primary lung adenocarcinoma (PLAC) and colorectal metastatic pulmonary tumor.

Methods

Pulmonary samples from 40 patients who underwent pulmonary resection for PLAC (20 tumors, 20 normal lungs) or pulmonary metastases originating from colorectal metastatic pulmonary tumor (CRMPT) (20 tumors, 20 normal lungs) were collected and analyzed retrospectively by probe electrospray ionization‐MS. AI using random forest (RF) algorithms was employed to evaluate the accuracy of each combination.

Results

The accuracy of the machine learning algorithm applied using RF to distinguish malignant tumor (PLAC or CRMPT) from normal lung was 100%. The algorithms offered 97.2% accuracy in differentiating PLAC and CRMPT.

Conclusions

MS combined with an AI system demonstrated high accuracy not only for differentiating cancer from normal tissue, but also for differentiating between PLAC and CRMPT with a short working time. This method shows potential for application as a support tool facilitating rapid intraoperative diagnosis to determine the surgical procedure for pulmonary resection.
Interhospital transport of critically ill patients: A prospective observational study of patient and transport characteristics
Authors: Eiding Helge , Kongsgaard Ulf E. , Olasveengen Theresa M. , Heyerdahl Fridtjof
Published: November 2021

Background

The cohort of critically ill patients transported between Intensive Care Units (ICUs) in Norway has not been studied previously. The aim of this study was to describe the characteristics of patients and transports for different types of interhospital transfers and explore whether there were differences in morbidity and mortality between the different transfer categories and the general Norwegian ICU population.

Methods

All transports of critically ill adult patients transferred between two geographically different Intensive Care Units during a one‐year period were registered. Patient and transport data were obtained from The Norwegian Intensive Care Registry, The Norwegian Cause of Death Registry, the hospital Electronic Patient Journal, the Air Ambulance Journal System, and the Emergency Medical Communication Centre database.

Results

821 transports of 788 surgical and medical patients were enrolled. Simplified Acute Physiology Scores (SAPSII) were 43, 36 and 38 for urgent secondary transport, non‐urgent secondary transport and return transfers, respectively. These were comparable to nationwide SAPSII scores that were 40 for university hospitals and 34 for local hospitals during the same time period. The return transfers had a median SOFA‐score of 4.7 and 53% were mechanically ventilated. Only 33% of return transfers were performed by established teams.

Conclusion

Intensive care patients transferred between ICUs are as critically ill as the rest of the ICU population, with a similar morbidity and mortality. The return transfers of ICU‐patients appear under‐triaged compared to secondary transports in terms of allocated resources.
Indications and diagnosis‐specific features of maternal and neonatal peripartum intensive care unit admissions: A retrospective study
Authors: Taube Hamutal S. , Matot Idit , Levy Nadav , Goren Or , Marom Ronella , Weiniger Carolyn F.
Published: November 2021

Background

Although peripartum intensive care unit admission indications are well‐reported, clinical and laboratory details rarely are. We described admission indications and categorised laboratory values and vital signs according to admission diagnosis.

Methods

Retrospective Institutional Review Board approved study. We identified intensive care unit admission diagnosis, laboratory values and vital signs from patient charts. Groups were compared according to admission diagnoses. Data were analysed using descriptive statistics.

Results

We included 91 general intensive care unit admissions among 56,865 deliveries (2011–2015) with complete data. The most common admission diagnosis was postpartum haemorrhage followed by hypertensive diseases of pregnancy and respiratory complications. Women with postpartum haemorrhage had lower mean (standard deviation) platelet counts (120.2 (45.8) vs. 181.2 (109.9), p = .003) and temperatures (35.7 (1.1) vs. 36.5 (1.2), p = .002). Women with hypertensive diseases of pregnancy had higher mean (standard deviation) blood pressures (systolic 150.4 (29.1) vs. 127.4 (21.0), p = .013, diastolic 100.3 (18.7) vs. 76.1 (16.1), p = .001), creatinine (1.1 (0.6) vs. 0.8 (0.3), p = .003), urea (14.6 (7.7) vs. 10.5 (4.7), p = .005) and liver enzymes, including aspartate transaminase (258.4 (297.0) vs. 41.4 (42.9), p = .000), alanine transaminase (184.4 (199.2) vs. 35.1 (75.9), p = .000), and alkaline phosphatase (166.6 (112.6) vs. 96.0 (60.0), p = .006). Women with respiratory complications had lower mean (standard deviation) oxygen saturations (93.7 (6.1) vs. 98.0 (2.6), p = .000), and higher mean (standard deviation) temperatures (37.1 (0.8) vs. 36.0 (1.2), p = .001).

Conclusions

We report differences in laboratory values and vital signs, according to intensive care unit admission diagnosis. Recognising these differences might help individualise patient assessment and care.
α‐synuclein suppresses microglial autophagy and promotes neurodegeneration in a mouse model of Parkinson’s disease
Authors: Tu Hai‐Yue , Yuan Bao‐Shi , Hou Xiao‐Ou , Zhang Xiao‐Jun , Pei Chong‐Shuang , Ma Ya‐Ting , Yang Ya‐Ping , Fan Yi , Qin Zheng‐Hong , Liu Chun‐Feng , Hu Li‐Fang
Published: November 2021

The cell‐to‐cell transfer of α‐synuclein (α‐Syn) greatly contributes to Parkinson's disease (PD) pathogenesis and underlies the spread of α‐Syn pathology. During this process, extracellular α‐Syn can activate microglia and neuroinflammation, which plays an important role in PD. However, the effect of extracellular α‐Syn on microglia autophagy is poorly understood. In the present study, we reported that extracellular α‐Syn inhibited the autophagy initiation, as indicated by LC3‐II reduction and p62 protein elevation in BV2 and cultured primary microglia. The in vitro findings were verified in microglia‐enriched population isolated from α‐Syn‐overexpressing mice induced by adeno‐associated virus (AAV2/9)‐encoded wildtype human α‐Syn injection into the substantia nigra (SN). Mechanistically, α‐Syn led to microglial autophagic impairment through activating toll‐like receptor 4 (Tlr4) and its downstream p38 and Akt‐mTOR signaling because Tlr4 knockout and inhibition of p38, Akt as well as mTOR prevented α‐Syn‐induced autophagy inhibition. Moreover, inhibition of Akt reversed the mTOR activation but failed to affect p38 phosphorylation triggered by α‐Syn. Functionally, the in vivo evidence showed that lysozyme 2 Cre (Lyz2cre)‐mediated depletion of autophagy‐related gene 5 (Atg5) in microglia aggravated the neuroinflammation and dopaminergic neuron losses in the SN and exacerbated the locomotor deficit in α‐Syn‐overexpressing mice. Taken together, the results suggest that extracellular α‐Syn, via Tlr4‐dependent p38 and Akt‐mTOR signaling cascades, disrupts microglial autophagy activity which synergistically contributes to neuroinflammation and PD development.
Observation unit use among patients with cancer following emergency department visits: Results of a multicenter prospective cohort from CONCERN
Authors: Klotz Adam D. , Caterino Jeffrey M. , Durham Danielle , Felipe Rico Juan , Pallin Daniel J. , Grudzen Corita R. , McNaughton Caroline , Marcelin Isabelle , Abar Beau , Adler David , Bastani Aveh , Bernstein Steven L. , Bischof Jason J. , Coyne Christopher J. , Henning Daniel J. , Hudson Matthew F. , Lyman Gary H , Madsen Troy E. , Reyes‐Gibby Cielito C. , Ryan Richard J. , Shapiro Nathan I. , Swor Robert , Thomas Charles R. , Venkat Arvind , Wilson Jason , Jim Yeung Sai‐Ching , Yilmaz Sule , Stutman Robin , Baugh Christopher W.
Published: November 2021

Purpose

Emergency department (ED) visits by patients with cancer frequently end in hospitalization. As concerns about ED and hospital crowding increase, observation unit care may be an important strategy to deliver safe and efficient treatment for eligible patients. In this investigation, we compared the prevalence and clinical characteristics of cancer patients who received observation unit care with those who were admitted to the hospital from the ED.

Methods

We performed a multicenter prospective cohort study of patients with cancer presenting to an ED affiliated with one of 18 hospitals of the Comprehensive Oncologic Emergency Research Network (CONCERN) between March 1, 2016 and January 30, 2017. We compared patient characteristics with the prevalence of observation unit care usage, hospital admission, and length of stay.

Results

Of 1051 enrolled patients, 596 (56.7%) were admitted as inpatients, and 72 (6.9%) were placed in an observation unit. For patients admitted as inpatients, 23.7% had a length of stay ≤2 days. The conversion rate from observation to inpatient was 17.1% (95% CI 14.6–19.4) among those receiving care in an observation unit. The average observation unit length of stay was 14.7 h. Patient factors associated ED disposition to observation unit care were female gender and low Charlson Comorbidity Index.

Conclusion

In this multicenter prospective cohort study, the discrepancy between observation unit care use and short inpatient hospitalization may represent underutilization of this resource and a target for process change.
Phase 1 trial of intraperitoneal paclitaxel in combination with intravenous cisplatin and oral capecitabine in patients with advanced gastric cancer and peritoneal metastases (IPGP study)
Authors: Vatandoust Sina , Bright Tim , Roy Amitesh Chandra , Abbas Muhammad Nazim , Watson David Ian , Gan Susan , Bull Jeff , Sorich Michael , Scott‐Hoy Alex , Luu Lee‐Jen , Karapetis Christos Stelios
Published: November 2021

Aims

Gastric cancer with peritoneal involvement has a poor prognosis. Intraperitoneal (IP) paclitaxel has shown promising results in these patients. However, this approach has only been studied in the Asian population, and in combination with S‐1. We investigated the maximum tolerated dose of IP paclitaxel, with a standard chemotherapy combination, in the Australian population.

Methods

The study of the population included metastatic human epidermal growth factor receptor 2 (HER2) negative gastric adenocarcinoma with peritoneal involvement. Treatment included six 21‐day cycles of cisplatin (80 mg/m2 IV, day 1) plus capecitabine (1000 mg/m2 PO BD, days 1–14) plus IP paclitaxel (days 1 and 8). IP paclitaxel doses for cohort 1–3 were 10, 20, and 30 mg/m2, respectively, in a 3 + 3 standard dose‐escalation design.

Results

Fifteen patients were enrolled of which 6 were female and the median age was 63. Two patients developed dose‐limiting toxicities. No grade 4/5 toxicities were recorded. The maximum tolerated dose was not reached. Therefore, as defined by the study protocol, the recommended phase‐2 dose for IP paclitaxel was determined to be 30 mg/m2. The 12‐month survival rate was 46.7%, and the median survival was 11.5 months (interquartile range [IQR]: 15.3–6.9).

Conclusions

IP paclitaxel is safe in combination with cisplatin and capecitabine and the recommended phase‐2 dose is 30 mg/m2.
Regorafenib outcomes from the population based South Australian Metastatic Colorectal Cancer Registry
Authors: Alawawdeh Anas , Price Timothy , Karapetis Christos , Piantadosi Cynthia , Padbury Rob , Roy Amitesh , Maddern Guy , Moore James , Carruthers Scott , Roder David , Townsend Amanda R.
Published: November 2021

Aim

Reviewing outcomes of regorafenib use in metastatic colorectal cancer using real‐world data from the South Australian Metastatic Colorectal Cancer Registry.

Methods

A retrospective review of the characteristics and outcomes of patients who received regorafenib in the Registry up to December 2018. The registry started in February 2006.

Results

Fifty‐three patients received regorafenib therapy since approved by the therapeutic goods administration in November 2013. The median age was 66 (range 34–82). 66% were male, 66% had stage IV disease at diagnosis, 53% had liver only involvement, whereas 13% had liver and lung disease and 6% had lung only involvement. 75% had left‐sided primary. KRAS was available in 35/53 patients with 49% of them being WT. BRAF status was known in 8/53 with 25% of them having a mutated variant. MSI testing was known in 14 patients in whom 21% of them had MSI‐High tumors. Prior lines of treatment received: one line 4%, two 9%, three 23%, four 26%, >four 37%. Prior biological use: bevacizumab 72%, anti‐EGFR 100% (for RAS WT). Median survival from diagnosis was 3.3 years (95% CI, 2.8–3.8 years). Median survival from the start of regorafenib was 7.1 months (95% CI, 4.8–9.4 months) and the 12‐month survival rate was 28%.

Conclusion

The survival outcome for those patients from our population‐based registry who access regorafenib is in keeping with reports from large, randomized trials. Thus, clinicians can quote local real world data when discussing efficacy and access to regorafenib therapy for mCRC patients.
Watching fracking
Authors: SZOLUCHA ANNA
Published: November 2021

The UK government's efforts to facilitate shale gas exploration have been matched by a surge of public opposition. The latter has manifested in a broad spectrum of activities in which local communities have “watched fracking”—meaning they have observed, protested, and filmed outside the drilling site, often taking note of when the pumps start and stop. Drawing on ethnographic fieldwork in northwest England, I analyze residents’ various “watching” activities as one dynamic through which they sought to mediate situated modes of sociopolitical erasure. Watching fracking was a form of directly participating in public matters, compensating the watchers for the state's perceived failures and those of corporate models of community engagement. It also helped members of the anti‐fracking community distance themselves from the state and their own feelings of alienation. By thus highlighting how disappointment with state formations interacts with an activist subjectivity, anthropologists can deepen our understanding of the changing relationship between state and society. [fracking, public engagement, state, citizen science, protest, extractive industry, Lancashire, United Kingdom]
Role of the supinator muscle in the pathophysiological mechanism of a pulled elbow
Authors: Kimura Masahiko
Published: November 2021

A pulled elbow is a common childhood orthopaedic injury that is usually caused by longitudinal traction on the hand. The pathophysiological mechanism of a pulled elbow involves interposition of the annular ligament into the radiohumeral joint. Recent ultrasonographic studies have shown that both the supinator muscle and annular ligament were trapped into the radiohumeral joint. This paper discusses why pulled elbows can occur during pronation and how a pulled elbow can be reduced either by hyperpronation or supination followed by elbow flexion based on the function of the supinator muscle.
Acute drug poisonings leading to hospitalization
Authors: Andersen Charlotte Uggerhøj , Nielsen Lars Peter , Møller Jørn Munkhof , Olesen Anne Estrup
Published: November 2021

Knowledge about current trends and epidemiology in poisonings is important to maintain quality in diagnostics, treatment and prevention. We performed a cross‐sectional study of all cases (n = 261) admitted with drug poisoning to Aalborg University Hospital during 1 year in 2017–2018. Median age was 30 (22–49) years, and 58% were female. Fifty percent were suicide attempts. In most cases, involved drugs were identified by history taking; blood analysis barely revealed any additional paracetamol and salicylicate poisonings. Drugs prescribed to the patient or available over the counter were involved in nearly two thirds of cases. Weak analgesics dominated by paracetamol (n = 91, 35%) was the most frequently involved group of drugs followed by opioids and benzodiazepines. Gender differences were observed with respect to involvement of weak analgesics and central stimulants. A higher prevalence of unidentified involved drugs was observed in 26 cases (10%) in which the length of admission exceeded 2 days and/or intensive care was needed. No deaths, cardiac arrhythmias or physical complications occurred. Thus, current handling of the acute poisoning seems effective in most cases. However, a more tailored use of blood analyses including a toxicological screen in selected cases may represent an opportunity for improvement.
Home pharmacological therapy in early COVID‐19 to prevent hospitalization and reduce mortality: Time for a suitable proposal
Authors: Pandolfi Sergio , Chirumbolo Salvatore , Ricevuti Giovanni , Valdenassi Luigi , Bjørklund Geir , Lysiuk Roman , Doşa Monica Daniela , Lenchyk Larysa , Fazio Serafino
Published: November 2021

The COVID‐19 pandemic is a highly dramatic concern for mankind. In Italy, the pandemic exerted its major impact throughout the period of February to June 2020. To date, the awkward amount of more than 134,000 deaths has been reported. Yet, post‐mortem autopsy was performed on a very modest number of patients who died from COVID‐19 infection, leading to a first confirmation of an immune‐thrombosis of the lungs as the major COVID‐19 pathogenesis, likewise for SARS. Since then (June–August 2020), no targeted early therapy considering this pathogenetic issue was approached. The patients treated with early anti‐inflammatory, anti‐platelet, anticoagulant and antibiotic therapy confirmed that COVID‐19 was an endothelial inflammation with immuno‐thrombosis. Patients not treated or scarcely treated with the most proper and appropriate therapy and in the earliest, increased the hospitalization rate in the intensive care units and also mortality, due to immune‐thrombosis from the pulmonary capillary district and alveoli. The disease causes widespread endothelial inflammation, which can induce damage to various organs and systems. Therapy must be targeted in this consideration, and in this review, we demonstrate how early anti‐inflammatory therapy may treat endothelia inflammation and immune‐thrombosis caused by COVID‐19, by using drugs we are going to recommend in this paper.
Structural and molecular determinants of mineralocorticoid receptor signalling
Authors: Grossmann Claudia , Almeida‐Prieto Brian , Nolze Alexander , Alvarez de la Rosa Diego
Published: November 2021

During the past decades, the mineralocorticoid receptor (MR) has evolved from a much‐overlooked member of the steroid hormone receptor family to an important player, not only in volume and electrolyte homeostasis but also in pathological changes occurring in an increasing number of tissues, especially the renal and cardiovascular systems. Simultaneously, a wealth of information about the structure, interaction partners and chromatin requirements for genomic signalling of steroid hormone receptors became available. However, much of the information for the MR has been deduced from studies of other family members and there is still a lack of knowledge about MR‐specific features in ligand binding, chromatin remodelling, co‐factor interactions and general MR specificity‐conferring mechanisms that can completely explain the differences in pathophysiological function between MR and its closest relative, the glucocorticoid receptor. This review aims to give an overview of the current knowledge of MR structure, signalling and co‐factors modulating its activity.

LINKED ARTICLES

This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone‐Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc
Diagnostic accuracy outcomes of office‐based (outpatient) biopsies in patients with laryngopharyngeal lesions: A systematic review
Authors: Owusu‐Ayim Mervyn , Ranjan Sushil R. , Lim Alison E. , Rogers Alexander D. G. , Montgomery Jenny , Flach Susanne , Manickavasagam Jaiganaesh
Published: November 2021

Background

In‐office biopsies (IOB) using local anaesthetic for laryngopharyngeal tumours has become an increasingly popular approach since the advent of distal chip endoscopes. Although a wide range of studies advocate use in clinical practice, the widespread application of the procedure is hampered by concerns regarding diagnostic accuracy.

Objective

To assess the diagnostic accuracy of IOB performed via flexible endoscopy. In addition, to analyse modifiable factors that may affect diagnostic accuracy of IOB.

Design

A systematic review following the PRISMA guidelines was conducted. PubMed, EMBASE, the Cochrane Library, Web of Science and CINAHL were used in the literature database search. Quality assessment of included studies was perfomed using the Newcastle‐Ottawa Scale.

Results

A total of 875 studies were identified, 16 of which were included into the systematic review; 1572 successful biopsies were performed using flexible endoscopy; 1283 cases were accurately diagnosed in the outpatient setting (81.6%) and 289 samples did not provide an accurate diagnosis (18.4%). The median sensitivity of IOB was 73%, and the specificity was 96.7%. Analysis of variable factors did not show any significant differences in method of approach, size of equipment (forceps) and additional lighting system or learning curve.

Conclusion

IOB are a viable tool for diagnostic workup of laryngopharyngeal tumours. Clinicians should be wary of reported limitations of IOB when benign or pre‐malignant diagnoses are made. In cases suspicious of malignancy, confirmatory investigation should be conducted.
Sorafenib attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis via HIF‐1α/SLC7A11 pathway
Authors: Yuan Siyu , Wei Can , Liu Guofang , Zhang Lijun , Li Jiahao , Li Lingling , Cai Shiyi , Fang Ling
Published: November 2021

Objectives

Evidences demonstrate that sorafenib alleviates liver fibrosis via inhibiting HSC activation and ECM accumulation. The underlying mechanism remains unclear. Ferroptosis, a novel programmed cell death, regulates diverse physiological/pathological processes. In this study, we aim to investigate the functional role of HSC ferroptosis in the anti‐fibrotic effect of sorafenib.

Materials and Methods

The effects of sorafenib on HSC ferroptosis and ECM expression were assessed in mouse model of liver fibrosis induced by CCl4. In vitro, Fer‐1 and DFO were used to block ferroptosis and then explored the anti‐fibrotic effect of sorafenib by detecting α‐SMA, COL1α1 and fibronectin proteins. Finally, HIF‐1α siRNA, plasmid and stabilizers were applied to assess related signalling pathway.

Results

Sorafenib attenuated liver injury and ECM accumulation in CCl4‐induced fibrotic livers, accompanied by reduction of SLC7A11 and GPX4 proteins. In sorafenib‐treated HSC‐T6 cells, ferroptotic events (depletion of SLC7A11, GPX4 and GSH; accumulation iron, ROS and MDA) were discovered. Intriguingly, these ferroptotic events were not appeared in hepatocytes or macrophages. Sorafenib‐elicited HSC ferroptosis and ECM reduction were abrogated by Fer‐1 and DFO. Additionally, both HIF‐1α and SLC7A11 proteins were reduced in sorafenib‐treated HSC‐T6 cells. SLC7A11 was positively regulated by HIF‐1α, inactivation of HIF‐1α/SLC7A11 pathway was required for sorafenib‐induced HSC ferroptosis, and elevation of HIF‐1α could inhibit ferroptosis, ultimately limited the anti‐fibrotic effect.

Conclusions

Sorafenib triggers HSC ferroptosis via HIF‐1α/SLC7A11 signalling, which in turn attenuates liver injury and fibrosis.
Changing Chinese Diets to Achieve a Win–Win Solution for Health and the Environment
Authors: Sheng Fangfang , Wang Jingjing , Chen Kevin Z. , Fan Shenggen , Gao Haixiu
Published: November 2021

Diets are key determinants of nutrition and health and play a significant role in the environment. In this article, we aim to (i) describe dietary transitions and health in China and the consequent environmental challenges; (ii) identify differences between current Chinese diets and healthy reference diets; (iii) conduct a systematic review assessing the health impacts of four reference diets on the Chinese population, and (iv) simulate changes in greenhouse gas emissions under different diet scenarios. The results show differences between the Chinese diets and reference diets, with the current Chinese diet including mainly grains (especially refined rice), excessive meat consumption, and insufficient consumption of fruit and milk. If all Chinese consumers adopt one of the healthy reference diets all the time, the incidence of diet‐related chronic disease and mortality would be significantly reduced. Such dietary shifts would also reduce greenhouse gas emissions by 146–202 million tons (18–25 percent) compared with the projected emissions level in 2030.
The effect of the Affordable Care Act Medicaid expansion on marriage
Authors: Hampton Matt , Lenhart Otto
Published: November 2021

This paper investigates the impact of the Affordable Care Act Medicaid expansions on marital behavior. We use data from the American Community Survey from 2008 to 2019 and estimate difference‐in‐differences models to test for effects on marriage and divorce outcomes. We find that expansions led to a 0.95% reduction in marriage stock and a 2.22% increase in divorce stock, with effects being larger among low educated individuals. We believe that two factors play a role as underlying mechanisms: (1) reduced reliance on spousal insurance coverage and (2) deciding to forego marriage or get divorced to meet eligibility restrictions.
Mental health outcomes and help‐seeking behaviours among Egyptian medical students: A cross‐sectional study
Authors: Kamel Mostafa M. , Westenberg Jean N. , Suen Janet , Jang Kerry L. , Maragha Tala , Badawy Adel , El‐Sawi Hosam , Krausz Michael
Published: November 2021

Aim

Approximately half of the population in Egypt is under the age of 25. Globally, mental illness represents the highest burden of disease in this age group. Yet in Egypt, there is still no youth‐specific mental health system in place and the vast majority of young people do not have access to any professional mental health support. The objective of this study was to describe the mental health needs of Egyptian youth and the resources they use when seeking help.

Methods

An online cross‐sectional survey was distributed among medical students at Tanta University in Egypt. Of the 707 individuals who completed the survey (90.9% response rate), 60.5% were female, 62.0% lived in urban and suburban areas, and the mean age of the sample was 20.5 (±1.8) years old.

Results

More than half (54%) of the students reported that they had been affected by mental health problems at some point in their lives. Anxiety and depression were the most common problems. Regarding help‐seeking behaviours, participants mainly searched the web or spoke to peers and relatives; few reported approaching medical professionals. The majority of participants (59.7%) reported being disappointed with the current mental health care system in Egypt.

Conclusions

There is a high prevalence of mental challenges among Egyptian youth and the health care system is not adequately prepared to respond to their needs. E‐Mental Health and online interventions seem to be a promising solution that could increase access to mental health services for Egyptian youth.
Mild early‐life stress exaggerates the impact of acute stress on corticolimbic resting‐state functional connectivity
Authors: Wang Huan , van Leeuwen Judith M. C. , de Voogd Lycia D. , Verkes Robbert‐Jan , Roozendaal Benno , Fernández Guillén , Hermans Erno J.
Published: November 2021

Abundant evidence shows that early‐life stress (ELS) predisposes for the development of stress‐related psychopathology when exposed to stressors later in life, but the underlying mechanisms remain unclear. To study predisposing effects of mild ELS on stress sensitivity, we examined in a healthy human population the impact of a history of ELS on acute stress‐related changes in corticolimbic circuits involved in emotional processing (i.e., amygdala, hippocampus and ventromedial prefrontal cortex [vmPFC]). Healthy young male participants (n = 120) underwent resting‐state functional magnetic resonance imaging (fMRI) in two separate sessions (stress induction vs. control). The Childhood Trauma Questionnaire (CTQ) was administered to index self‐reported ELS, and stress induction was verified using salivary cortisol, blood pressure, heart rate and subjective affect. Our findings show that self‐reported ELS was negatively associated with baseline cortisol, but not with the acute stress‐induced cortisol response. Critically, individuals with more self‐reported ELS exhibited an exaggerated reduction of functional connectivity in corticolimbic circuits under acute stress. A mediation analysis showed that the association between ELS and stress‐induced changes in amygdala–hippocampal connectivity became stronger when controlling for basal cortisol. Our findings show, in a healthy sample, that the effects of mild ELS on functioning of corticolimbic circuits only become apparent when exposed to an acute stressor and may be buffered by adaptations in hypothalamic–pituitary–adrenal axis function. Overall, our findings might reveal a potential mechanism whereby even mild ELS might confer vulnerability to exposure to stressors later in adulthood.
Beyond adaptive preferences: Rethinking women's complicity in their own subordination
Authors: Knowles Charlotte
Published: November 2021

An important question confronting feminist philosophers is why women are sometimes complicit in their own subordination. The dominant view holds that complicity is best understood in terms of adaptive preferences. This view assumes that agents will naturally gravitate away from subordination and towards flourishing as long as they do not have things imposed on them that disrupt this trajectory. However, there is reason to believe that ‘impositions’ do not explain all of the ways in which complicity can arise. This paper defends a phenomenological account of complicity, which offers an alternative explanation.
Forecasting high‐frequency excess stock returns via data analytics and machine learning
Authors: Akyildirim Erdinc , Nguyen Duc Khuong , Sensoy Ahmet , Šikić Mario
Published: November 2021

Borsa Istanbul introduced data analytics to present additional information about its market conditions. We examine whether this product can be utilized via various machine learning methods to predict intraday excess returns. Accordingly, these analytics provide significant prediction ratios above 50% with ideal profit ratios that can reach up to 33%. Among all the methods considered, XGBoost (logistic regression) performs better in predicting excess returns in the long‐term analysis (short‐term analysis). Results provide evidence for the benefits of both the analytics and the machine learning methods and raise further discussion on the semistrong market efficiency.
Deficiency of the paternally inherited gene Magel2 alters the development of separation‐induced vocalization and maternal behavior in mice
Authors: Bosque Ortiz Gabriela M. , Santana Gustavo M. , Dietrich Marcelo O.
Published: November 2021

The behavior of offspring results from the combined expression of maternal and paternal genes. Genomic imprinting silences some genes in a parent‐of‐origin specific manner, a process that, among all animals, occurs only in mammals. How genomic imprinting affects the behavior of mammalian offspring, however, remains poorly understood. Here, we studied how the loss of the paternally inherited gene Magel2 in mouse pups affects the emission of separation‐induced ultrasonic vocalizations (USV). Using quantitative analysis of more than 1000 USVs, we characterized the rate of vocalizations as well as their spectral features from postnatal days 6–12 (P6–P12), a critical phase of mouse development that covers the peak of vocal behavior in pups. Our analyses show that Magel2 deficient offspring emit separation‐induced vocalizations at lower rates and with altered spectral features mainly at P8. We also show that dams display altered behavior towards their own Magel2 deficient offspring at this age. In a test to compare the retrieval of two pups, dams retrieve wildtype control pups first and faster than Magel2 deficient offspring. These results suggest that the loss of Magel2 impairs the expression of separation‐induced vocalization in pups as well as maternal behavior at a specific age of postnatal development, both of which support the pups' growth and development.
Clinical outcomes after joint surgery in patients on turoctocog alfa pegol (N8‐GP) prophylaxis: A post hoc analysis
Authors: Hampton Kingsley , Tiede Andreas , Shivamurthy Shwetha , Chowdary Pratima
Published: November 2021

Introduction

Joint damage in haemophilia often requires surgical correction. However, the surgery effect on bleeding rates and other clinical joint outcomes can be unclear.

Aim

To investigate the effects of joint surgery on joint annualized bleeding rates (JABRs) and physical health outcomes in patients with haemophilia A undergoing N8‐GP prophylaxis.

Methods

Patients in the pathfinder 2 trial received N8‐GP prophylaxis, enrolling in the pathfinder 3 trial for indicated surgery. Patients returned to pathfinder 2 post‐surgery, continuing N8‐GP prophylaxis until end‐of‐trial. JABRs were calculated from bleeding across all joints for pre‐surgery (immediately before surgery) and post‐surgery (to pathfinder 2 study end) periods. Joint‐health‐related outcomes were derived from patient records.

Results

Data (41 joint surgeries; n = 30) were analysed statistically using datamining and descriptively. Pre‐surgery mean JABR was higher in patients who later were operated than in 146 non‐operated patients (p = .004). In operated patients, mean JABR decreased from 1.33 pre‐surgery to .37 post‐surgery (p = .011). In all but three patients, JABR improved or remained the same post‐surgery. In the three patients whose JABR remained at one (all with multiple joint arthropathy), post‐surgery bleeds were mostly at non‐operated sites. Two of the three patients whose JABR increased post‐surgery had undergone surgery for reasons unlikely to improve JABR. Mobility parameters often improved in patients whose JABR remained at zero.

Conclusion

Patients with haemophilia treated with N8‐GP prophylaxis benefit from surgeries. However, this analysis could not differentiate the relative contributions of surgical interventions and prophylactic treatment to the improvement of JABR.
Does social modeling increase infants’ willingness to accept unfamiliar foods?
Authors: DeJesus Jasmine M. , Venkatesh Shruthi
Published: November 2021

Despite a rich knowledge base about infants’ social learning and studies observing social referencing in other species in food contexts, we know surprisingly little about social learning about food among human infants. This gap in the literature is particularly surprising considering that feeding unfamiliar foods to infants is a very common experience as infants begin to eat solid foods. The present study examines whether parental social modeling influences infants’ willingness to accept unfamiliar foods. In two Zoom sessions, parents will be asked to feed unfamiliar foods to their 6‐ to 24‐month‐old infants (different unfamiliar foods in each session). In both sessions, infants’ food acceptance and rejection will be measured. In the first session, parents will be asked to do what they would typically do; spontaneous social modeling will be recorded. In the second session, parents will be instructed to model eating the unfamiliar food. We will examine associations between infants’ willingness to eat unfamiliar foods, parent social modeling, and extant parent and infant characteristics.
Increasing lobster processing margins through scenario linear programming
Authors: Fruytier Pierre‐André M. , Jensson Páll
Published: November 2021

In the lobster processing industry, savvy decision‐makers call for robust, fast, and cheap decision support systems to simulate scenarios in hard‐to‐predict market conditions for planning sales and operations of the next season. For optimizing the planning of simulated scenarios, linear programming models are customized to the constraints of each business case, and to data readily available from past seasons. For illustration, two significantly different cases are presented with results. Considerations regarding cross training and cell operations is discussed to resolve shifting bottlenecks and consequently improve financial performance. Depending on cases, direct margins could be improved by up to two‐digit rates.
Non‐pharmacological interventions using information and communication technology for behavioral and psychological symptoms of dementia: A systematic review and meta‐analysis protocol
Authors: Seok Jo Woon , Shin Jinhee , Kang Bada , Lee Hyangkyu , Cho Eunhee , Lee Kyung Hee
Published: November 2021

Aim

To review and examine the effectiveness of non‐pharmacological interventions on behavioural and psychological symptoms of dementia using information and communication technology.

Design

This is a systematic review and meta‐analysis.

Methods

The databases including PubMed, CINAHL with Full Text (EBSCOhost), PsycINFO, Embase, and the Cochrane Library will be searched for all published studies. Studies will be screened and selected with criteria described in PICOS format. Risk of bias will be assessed by the National Institute for Health and Clinical Excellence checklist. Data will be extracted from eligible studies and used to perform a meta‐analysis examining the overall effects and effects on individual outcomes. Additionally, we will conduct meta‐regression to examine the association between explanatory variables and behavioural and psychological symptoms. This study has been funded since June 2020.

Discussion

This study will be the first to reveal the effects of non‐pharmacological interventions using information and communication technology on behavioural and psychological symptoms of dementia. Furthermore, this study will provide updated and valid evidence of interventions using this for managing behavioural and psychological symptoms of dementia.

Impact

Although non‐pharmacological interventions using information and communication technology for older adults living with dementia are continuously developing, their direct effect remains unclear. This study will evaluate the effectiveness of these interventions on behavioural and psychological symptoms of dementia and provide the evidence to implement these interventions among older adults living with dementia. Thus, caregivers and nursing staff can manage behavioural and psychological symptoms of dementia more effectively by incorporating information and communication technology.
Development of a risk calculator to predict attention‐deficit/hyperactivity disorder in very preterm/very low birth weight newborns
Authors: Franz Adelar Pedro , Caye Arthur , Lacerda Bárbara Calil , Wagner Flávia , Silveira Rita C. , Procianoy Renato Soibelmann , Moreira‐Maia Carlos Renato , Rohde Luis Augusto
Published: November 2021

Background

Very preterm/very low birth weight (VP/VLBW) newborns can have lifelong morbidities, as attention‐deficit/hyperactivity disorder (ADHD). Clinicians have no markers to discriminate which among those individuals will develop later ADHD, based only on the clinical presentation at birth. Our aim was to develop an individualized risk calculator for ADHD in VP/VLBW newborns.

Methods

This retrospective prognostic study included a consecutive sample of all VP/VLBW children (gestational age <32 weeks and/or birth weight <1.5 kg) born between 2010 and 2012 from a clinical cohort in a Brazilian tertiary care hospital. Children were clinically assessed at 6 years of age for ADHD using the Schedule for Affective Disorders and Schizophrenia for School‐Age Children (K‐SADS). The least absolute shrinkage and selection operator (LASSO) method was used for model‐building.

Results

Ninety‐six VP/VLBW children were assessed at 6 years of age (92% follow‐up), of whom 32 (33%) were diagnosed with ADHD. The area under the ROC curve (AUC) for ADHD prediction based on seven parameters (late‐onset sepsis confirmed by blood culture, necrotizing enterocolitis, neonatal seizures, periventricular leukomalacia, respiratory distress syndrome, length of hospital stay, and number of maternal ADHD symptoms) was .875 (CI, 0.800–0.942, p < .001; AUC corrected for optimism with bootstrapping: .806), a performance that is comparable to other medical risk calculators. Compared to approaches that would offer early intervention to all, or intervention to none, the risk calculator will be more useful in selecting VP/VLBW newborns, with statistically significant net benefits at cost:benefits of around 1:2 to around 10:6 (range of ADHD risk thresholds of 32%–62%, respectively). It also showed specificity for ADHD compared to other prevalent child psychopathologies.

Conclusions

The risk calculator showed good performance for early identification of VP/VLBW newborns at high risk of future ADHD diagnosis. External validity in population‐based samples is needed to extend clinical usefulness.
Fluorine‐18 fluorodeoxyglucose positron emission tomography‐computed tomography for staging of canine insulinoma: 3 cases (2019–2020)
Authors: Walczak R. , Kawalilak L. , Griffin L.
Published: November 2021

Objectives

Canine insulinomas are uncommon malignant functional pancreatic neuroendocrine tumours with a high metastatic rate. Diagnostic imaging aids with staging and surgical planning of these tumours; however, identification is unpredictable across modalities. High‐grade human pancreatic neuroendocrine tumours display increased avidity on 18F‐fluorodeoxyglucose positron emission tomography‐CT.

Materials and Methods

Dogs with clinicopathologic findings consistent with pancreatic insulinoma were prospectively enrolled. Patients underwent 18F‐fluorodeoxyglucose positron emission tomography‐CT and CT angiography, followed by exploratory laparotomy.

Results

Three patients met the inclusion criteria and had histologically confirmed insulinomas. Both metastatic lesions in patient 1 were mildly avid (SUVmax 2.79 and 3.01). In patient 2, the primary pancreatic insulinoma was minimally avid (SUVmax 2.16). The primary pancreatic lesion in patient 3 had similar avidity to normal pancreatic parenchyma (SUVmax 1.54) and was undetected on 18F‐fluorodeoxyglucose positron emission tomography‐CT. Insulinomas demonstrated variable attenuation and contrast enhancement patterns on CT angiography and certain lesions were more conspicuous than on 18F‐fluorodeoxyglucose positron emission tomography‐CT. Two metastatic lesions not visible on either imaging modality were discovered in patient 2 at surgery.

Clinical Significance

Canine insulinomas were inconsistently avid on 18F‐fluorodeoxyglucose positron emission tomography‐CT. This finding is likely attributable to the confounding clinicopathological features and multifaceted transformation of these tumours, in addition to the influence of variable tumour size, composition and vascularity. Unpredictable tumoural avidity limits the value of 18F‐fluorodeoxyglucose positron emission tomography‐CT for staging canine insulinomas.
From a Molar to a Molecular Approach to the Developmental Trajectory of Syntax Comprehension of Persons with Intellectual Disability
Authors: Facon Bruno , Magis David , Knutsen Dominique
Published: November 2021

The aim of our study was to investigate whether the developmental trajectories of syntax comprehension of participants with or without intellectual disability are comparable. We obtained results from a syntax comprehension test of 615 typically developing participants (mean chronological age  =  4.61 years, SD  =  0.85) and 615 participants with intellectual disability (mean chronological age  =  12.22 years, SD  =  3.14) matched on a nonverbal cognitive measure. We examined these results by applying several statistical approaches to the overall scores for the syntax test and then to the scores for each of its 92 items. Results showed negligible between‐group differences in developmental trajectories, at both levels of analysis (overall and item scores). This lack of effect suggests that the relationship between cognitive development and syntax comprehension is comparable for the two groups of participants. Theoretical and practical implications of these findings are discussed.