bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute appendicitis during the clinical course of COVID‐19 in a 13‐year‐old boy: Complication or coincidental?
Authors: Nurullayev Elnur , Gördü Bilge , Özsürekçi Yasemin , Haliloglu Mithat , Soyer Tutku
Published: September 2021

Gastrointestinal symptoms appear to be one of the most common presentations of SARS‐CoV‐2 infection, later named COVID‐19. The symptoms such as nausea, emesis, abdominal pain, and diarrhoea may be recognised as either a finding of COVID‐19 or prominent presentation of multi‐inflammatory syndrome in children (MIS‐C). COVID‐19 may present with acute appendicitis and/or may mimic its clinical findings. Although, coexistence of acute appendicitis and COVID‐19 has been well documented, it is not clear whether appendicitis is a complication of COVID‐19 or coincidence in children. A 13‐year‐old boy who developed acute appendicitis during the clinical course of COVID‐19 is presented to discuss the possibility of causal relationship between appendicitis and COVID‐19 in children.
High Ki‐67 proliferation index and lack of chemotherapy are associated with reduced overall survival in patients with triple negative breast cancer: A retrospective cohort in a major breast centre in Hong Kong
Authors: Hung Ray Ka‐wai , Chiu Tiffany Hoi‐wun , Tsoi Yee‐kei , Chan Wing‐cheong
Published: September 2021

Background

Triple negative breast cancer (TNBC) is the most aggressive molecular subtype of breast cancer. The management of TNBC is challenging due to the lack of effective treatment. In this study, all patients diagnosed to have TNBC, managed in the Department of Surgery, North District Hospital, were identified and possible prognostic markers including age, menopausal status, Ki‐67 proliferation index, TNM stage and the treatment received by the patients were assessed for possible association on the overall survival rate.

Methods

The pathology results of patients diagnosed to have breast cancer from 2012 to 2017 were reviewed. Relevant information was retrieved by reviewing the clinical notes in the clinical management system retrospectively.

Result

A total of 169 patients with TNBC were identified. The 5‐year overall survival rate in this group of patients is 68%. In univariate analysis, age, high Ki‐67 proliferation index, T3 and T4 disease, lymph node involvement, distant metastasis, the lack of chemotherapy and the lack of radiotherapy are significant prognostic indicators. When analysing them in multivariate analysis, T4 disease (HR, 4.663; 95% CI, 1.209–17.988), lymph node involvement (2.361; 95% CI, 1.002–5.561), distant metastasis (2.262; 95% CI, 1.012–5.057), high Ki‐67 proliferation index (HR, 2.329; 95% CI, 1.026–5.278) and lack of chemotherapy (HR, 3.725; 95% CI, 1.247–11.123) remain statistically significant.

Conclusion

Beside advance disease status, high Ki‐67 proliferation index and lack of systemic chemotherapy are another two important prognostic factors in patients with triple negative breast cancer. Chemotherapy is strongly advised in patients with TNBC whenever they are medically fit.
Preliminary experience with indocyanine green lymphography during microsurgical subinguinal varicocelectomy
Authors: Cho Chak‐Lam , Chiu Peter Ka‐Fung , Chu Ringo Wing‐Hong
Published: September 2021

Objective

The aim of the present study was to evaluate the feasibility to expand the use of indocyanine green (ICG) to lymphatic‐sparing microsurgical subinguinal varicocelectomy (MSV) in addition to ICG angiogram by using video microsurgery platform.

Patients and Methods

Seven patients with 12 varicoceles had MSV and intraoperative ICG lymphography performed from July 2019 to February 2020. Intraoperative ICG lymphography was employed to confirm and preserve lymphatics after intra‐parenchymal testicular injection of ICG.

Results

Lymphatic vessels were clearly identified on ICG lymphography in all varicocele units with intra‐parenchymal testicular injection. ICG lymphography did not significantly interfere with the quality of subsequent ICG angiography in the majority of patients. All patients were discharged uneventfully within 24 h after the operation. No complications were reported with a median follow up duration of 9 months.

Conclusions

The use of intraoperative ICG lymphography consistently provides objective assessment of lymphatic vessels during the procedure of MSV.
Transarterial chemoembolisation plus stereotactic body radiotherapy as conversion therapy for large right lobe hepatocecullar carcinoma
Authors: Lam Tang‐yu , Wong Wai‐man , Lee Ching‐ching , Cheung Chin‐cheung
Published: September 2021

Huge right lobe hepatocecullar carcinoma (HCC) at presentation is not uncommon in Hong Kong. The aim of this study was to evaluate whether transarterial chemoembolisation (TACE) followed by stereotactic body radiotherapy (SBRT) can be used as a conversion therapy for huge right lobe HCC. We retrospectively reviewed two groups of patients with solitary huge right lobe HCC (defined as > = 10 cm in size) treated with direct surgery or conversion therapy (TACE + SBRT) first. From 2009 to 2014, 23 patients with huge right lobe HCC with resection done in our centre were reviewed. Eleven patients had direct surgery and 12 patients had received conversion therapy first. The mean tumour size for the conversion therapy group was significantly larger 13.9 cm versus 11.2 cm (p = .03). Patients in the conversion therapy group also had other unfavourable factors at presentation. Overall median survival for direct surgery group was 63 months while that of conversion therapy group was 40 months (p = .48). Operative time was 313 min for the direct surgery group versus 317 min for the conversion therapy group (p = .95). We concluded that TACE + SBRT can be a feasible conversion therapy for borderline resectable huge right lobe HCC.
Endoscopic submucosal dissection versus endoscopic mucosal resection for rectal carcinoid tumor. A meta‐analysis and meta‐regression with single‐arm analysis
Authors: Yong Jie Ning , Lim Xiong Chang , Nistala Kameswara Rishi Yeshayahu , Lim Lincoln Kai En , Lim Grace En Hui , Quek Jingxuan , Tham Hui Yu , Wong Neng Wei , Tan Ker‐Kan , Chong Choon Seng
Published: September 2021

Objective

As there has been so far no consensus on the best endoscopic resection technique, a meta‐analysis was conducted to compare the efficacy and safety of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for treating rectal carcinoid tumors.

Methods

MEDLINE and EMBASE databases were searched for articles on the treatment of rectal carcinoid tumors using ESD vs EMR published up to October 2020 for outcomes including en bloc and complete resection, margin involvement, procedure time, requirement for additional surgery, bleeding, perforation and recurrence. Risk ratio and weighted mean differences were used for a DerSimonian and Laird random effects pairwise meta‐analysis. Single‐arm meta‐analyses of proportions and random effects meta‐regression analysis were also conducted.

Results

Twenty‐two studies involving 1360 rectal carcinoid tumors were included, in which 655 and 705 rectal carcinoid tumors were resected with ESD and EMR, respectively. The resection efficacy of ESD was comparable to that of EMR for tumors <10 mm. However, there were a significantly higher complete resection rate, and lower rates of vertical margin involvement and requirement for additional surgery using ESD than using EMR for tumors ≤20 mm. ESD had a longer procedure time and an increased likelihood of bleeding than EMR.

Conclusions

ESD is more effective in providing a curative treatment for rectal carcinoid tumors ≤20 mm in size as ESD can achieve a higher complete resection rate with lower vertical margin involvement than EMR. While they are suitable for treating rectal carcinoid tumors <10 mm as both techniques provide similar efficacy.
An updated overview on the regulatory circuits of polyhydroxyalkanoates synthesis
Authors: Mitra Ruchira , Xu Tong , Chen Guo‐Qiang , Xiang Hua , Han Jing
Published: September 2021

Polyhydroxyalkanoates (PHA) are a promising and sustainable alternative to the petroleum‐based synthetic plastics. Regulation of PHA synthesis is receiving considerable importance as engineering the regulatory factors might help developing strains with improved PHA‐producing abilities. PHA synthesis is dedicatedly regulated by a number of regulatory networks. They tightly control the PHA content, granule size and their distribution in cells. Most PHA‐accumulating microorganisms have multiple regulatory networks that impart a combined effect on PHA metabolism. Among them, several factors ranging from global to specific regulators, have been identified and characterized till now. This review is an attempt to categorically summarize the diverse regulatory circuits that operate in some important PHA‐producing microorganisms. However, in several organisms, the detailed mechanisms involved in the regulation of PHA synthesis is not well‐explored and hence further research is needed. The information presented in this review might help researcher to identify the prevailing research gaps in PHA regulation.
An up‐to‐date review of cardiac pacemakers and implantable cardioverter defibrillators
Authors: Kuang Ronny JD , Pirakalathanan Janu , Lau Theodore , Koh Daniel , Kotschet Emily , Ko Brian , Lau Kenneth K
Published: September 2021

Cardiac pacemakers are one of the most frequently encountered cardiac devices seen on chest imaging. They may include single or dual chamber pacemakers, automated implantable cardioverter defibrillators (AICD), biventricular pacemakers used for cardiac resynchronisation therapy (CRT), wireless CRT, leadless pacemakers, and subcutaneous implantable cardioverter defibrillators (SICD). This review aims to provide an up‐to‐date review on current implantable pacemaker and defibrillator devices.
Effectiveness of an optimized text message and Internet intervention for smoking cessation: A randomized controlled trial
Authors: Graham Amanda L. , Papandonatos George D. , Cha Sarah , Amato Michael S. , Jacobs Megan A. , Cohn Amy M. , Abroms Lorien C. , Whittaker Robyn
Published: September 2021

Aims

To evaluate the effectiveness of a combined internet and text message intervention for smoking cessation compared with an internet intervention alone. The text message intervention was optimized for engagement in an earlier multiphase optimization (MOST) screening phase.

Design

A parallel, two‐group, individually randomized clinical trial (RCT) was conducted in a MOST confirming phase. Recruitment spanned December 2018 to March 2019. Follow‐up was conducted at 3 and 9 months, beginning March 2019 and ending January 2020.

Setting

United States: a digital study conducted among new registrants on a free tobacco cessation website.

Participants

Eligible individuals were 618 adult current smokers in the United States, age 18 years or older who signed up for text messages during website registration (67.2% female, 70.4% white).

Interventions

The treatment arm (WEB+TXT; n = 311) received access to the website and text messaging. The control arm (WEB; n = 307) received access to the website alone.

Measurements

The primary outcome was self‐reported 30‐day point prevalence abstinence (ppa) at 9 months post‐randomization analyzed under intent to treat (ITT), counting non‐responders as smoking. Secondary outcomes included 3‐month measures of 30‐day ppa, intervention engagement and intervention satisfaction.

Findings

Abstinence rates at 9 months were 23.1% among WEB+TXT and 23.2% among WEB (OR = 1.00, 95% CI = 0.69–1.45; P = 0.99). WEB+TXT increased engagement with 5 of 6 interactive features (standardized mean difference (SMD) = 0.26–0.47, all P < 0.001) and repeat website visits (48.7% vs 38.9%, SMD = 0.14, P = 0.02). Satisfaction metrics favored WEB+TXT (satisfied: 96.3% vs 90.5%, SMD = 0.17, P = 0.008; recommend to friend: 95.9% vs 90.1%, SMD = 0.16, P = 0.028).

Conclusions

A randomized controlled trial found no evidence that a combined internet and text message intervention for smoking cessation compared with an internet intervention alone increased 9‐month abstinence rates among adult current smokers in the United States, despite evidence of higher levels of intervention engagement and satisfaction at 3 months.
Genome‐wide analysis reveals genetic overlap between alcohol use behaviours, schizophrenia and bipolar disorder and identifies novel shared risk loci
Authors: Wiström Erik D. , O'Connell Kevin S. , Karadag Naz , Bahrami Shahram , Hindley Guy F. L. , Lin Aihua , Cheng Weiqiu , Steen Nils Eiel , Shadrin Alexey , Frei Oleksandr , Djurovic Srdjan , Dale Anders M. , Andreassen Ole A. , Smeland Olav B.
Published: September 2021

Background and aim

Schizophrenia (SCZ) and bipolar disorder (BD) have a high comorbidity of alcohol use disorder (AUD), and both comorbid AUD and excessive alcohol consumption (AC) have been linked to greater illness severity. We aimed to identify genomic loci jointly associated with SCZ, BD, AUD and AC to gain further insights into their shared genetic architecture.

Design

We analysed summary data (P values and Z scores) from genome‐wide association studies (GWAS) using conjunctional false discovery rate (conjFDR) analysis, which increases power to discover shared genomic loci. We functionally characterized the identified loci using publicly available biological resources.

Setting

AUD and AC data provided by the Million Veteran Program, derived from the United States Department of Veterans Affairs Healthcare System. SCZ and BD data provided by the Psychiatric Genomics Consortium, based on cohorts from countries in Europe, North America and Australia.

Participants

AUD (34 658 cases, 167 346 controls), AC (n = 200 680), SCZ (31 013 cases and 38 918 controls), BD (20 352 cases and 31 358 controls). All participants were of European ancestry.

Measurements

Genomic loci shared between alcohol traits, SCZ and BD at conjFDR <0.05.

Findings

Conditional Q‐Q plots showed single‐nucleotide polymorphism (SNP) enrichment for both alcohol traits across different levels of significance with SCZ and BD, and vice versa. Using conjFDR analysis we leveraged this genetic enrichment and identified several loci shared between SCZ and AUD (n = 28) and AC (n = 24), BD and AUD (n = 2) and AC (n = 8) at conjFDR <0.05. Among these loci, 24 are novel for AUD, 15 are novel for AC, three are novel for SCZ and one is novel for BD. There was a mixture of same and opposite effect directions among the shared loci.

Conclusions

Alcohol use disorder and alcohol consumption share genomic loci with the psychiatric disorders schizophrenia and bipolar disorder with a mixed pattern of effect directions, indicating a complex genetic relationship between the phenotypes.
Trends towards revealing the genetic architecture of sheep tail patterning: Promising genes and investigatory pathways
Authors: Kalds P. , Luo Q. , Sun K. , Zhou S. , Chen Y. , Wang X.
Published: September 2021

Different sheep breeds have evolved after initial domestication, generating various tail phenotypic patterns. The phenotypic diversity of sheep tail patterns offers ideal materials for comparative analysis of its genetic basis. Evolutionary biologists, animal geneticists, breeders, and producers have been curious to clearly understand the underlying genetics behind phenotypic differences in sheep tails. Understanding the causal gene(s) and mutation(s) underlying these differences will help probe an evolutionary riddle, improve animal production performance, promote animal welfare, and provide lessons that help comprehend human diseases related to fat deposition (i.e., obesity). Historically, fat tails have served as an adaptive response to aridification and climate change. However, the fat tail is currently associated with compromised mating and animal locomotion, fat distribution in the animal body, increased raising costs, reduced consumer preference, and other animal welfare issues such as tail docking. The developing genomic approaches provide unprecedented opportunities to determine causal variants underlying phenotypic differences among populations. In the last decade, researchers have performed several genomic investigations to assess the genomic causality underlying phenotypic variations in sheep tails. Various genes have been suggested with the prominence of several potentially significant causatives, including the BMP2 and PDGFD genes associated with the fat tail phenotype and the TBXT gene linked with the caudal vertebrae number and tail length. Although the potential genes related to sheep tail characteristics have been revealed, the causal variant(s) and mutation(s) of these high‐ranking candidate genes are still elusive and need further investigation. The review discusses the potential genes, sheds light on a knowledge gap, and provides possible investigative approaches that could help determine the specific genomic causatives of sheep tail patterns. Besides, characterizing and revealing the genetic determinism of sheep tails will help solve issues compromising sheep breeding and welfare in the future.
Cigarette, e‐cigarette, and dual use during the third trimester of pregnancy in a national sample of heterosexual and sexual minority women
Authors: Beck Dana C. , Veliz Phil T. , McCabe Sean E. , Boyd Carol J. , Evans‐Polce Rebecca
Published: September 2021

Background and Objectives

Research investigating e‐cigarettes/e‐products and dual use with cigarettes among pregnant sexual minority individuals in the United States is lacking. This study addresses this gap using a national sample.

Methods

Two waves of national panel data (2015–2018) from the Population Assessment of Tobacco and Health study were used. The sample included 1842 women, 237 identified as sexual minorities (n = 17 lesbian, n = 177 bisexual, n = 43 something else), who indicated pregnancy during the past 12 months at Waves 3 or 4. Covariates included race, ethnicity, past‐year income, and education. Cigarette, e‐cigarette, or dual use was examined during the last trimester.

Results

Sexual minorities had higher adjusted odds of cigarette use during their last trimester of pregnancy relative to heterosexual women (adjusted odds ratio [AOR] = 1.55, 95% confidence interval [CI] = 1.08, 2.23). Bisexual women had higher odds of smoking cigarettes during their third trimester compared with heterosexual women (AOR = 1.82, 95% CI = 1.21, 2.72). Lesbian women were more likely to use e‐cigarettes/e‐products (AOR = 9.15, 95% CI = 2.29, 36.5) and indicate dual use (AOR = 6.00, 95% CI = 1.43, 25.1) during their third trimester of pregnancy compared with heterosexual women.

Conclusion and Scientific Significance

Maternal health among US sexual minority women would benefit from clinicians equipped to provide accurate information and support for Food and Drug Administration‐approved smoking cessation, information about e‐cigarettes/e‐products, and dual use. This study is the first to examine cigarette, e‐cigarette, and dual use during the third trimester of pregnancy using a national sample, with specific attention to differences in sexual orientation.
Seasonal agricultural activity and crime
Authors: Charlton Diane , James Alexander , Smith Brock
Published: September 2021

Sudden shocks to labor demand have sometimes been shown to increase local crime rates. We build on this literature by estimating the causal effect of labor‐intensive seasonal agricultural activity on crime. We analyze a unique data set that describes criminal activity and fruit, vegetable, and horticultural (FVH) employment by month and U.S. county from 1990 to 2016. We find that the FVH labor share is associated with reduced property and violent crime rates, and possibly the number of property crimes committed within county years. Examining heterogeneities based on ethnicity, labor‐intensive FVH activity decreases the rate of non‐Hispanic arrests and victimization, and increases the number of Hispanic arrests and victims (consistent with rising local Hispanic populations). Taken together, results are broadly consistent with the idea that agricultural harvest of labor‐intensive crops enhances local labor market opportunities that reduce incentives to commit crimes. Results are robust to a battery of alternative specifications that address the inherent challenges associated with measuring seasonal agricultural labor.
Non‐invasive prenatal diagnosis for translocation carriers—YES please or NO go?
Authors: Srebniak Malgorzata I. , Jehee Fernanda S. , Joosten Marieke , Boter Marjan , de Valk Walter G. , van der Helm Robert , Sistermans Erik A. , Voorhoeve Els , Bhola Shama , Hoffer Mariette J. V. , den Hollander Nicolette , Macville Merryn V. E. , Van Opstal Diane
Published: September 2021

Introduction

The presence of an unbalanced familial translocation can be reliably assessed in the cytotrophoblast of chorionic villi. However, carriers of a balanced translocation often decline invasive testing. This study aimed to investigate whether an unbalanced translocation can also be diagnosed in cell free DNA by whole‐genome non‐invasive prenatal screening (NIPS).

Material and methods

Pregnant women carrying a fetus with an unbalanced familial translocation, for whom NIPS as well as microarray data were available, were included in this retrospective assessment. NIPS was performed in the course of the TRIDENT study.

Results

In 12 cases, both NIPS and microarray data were available. In 10 of 12 cases the unbalanced translocation was correctly identified by NIPS without prior knowledge on parental translocation. One was missed because the fetal fraction was too low. One was missed because of technical restrictions in calling 16p gains.

Conclusions

This study supports the hypothesis that routine NIPS may be used for prenatal diagnosis of unbalanced inheritance of familial translocations, especially with prior knowledge of the translocation allowing focused examination of the involved chromosomal regions. Our study showed that routine shallow sequencing designed for aneuploidy detection in cell free DNA may be sufficient for higher resolution NIPS, if specialized copy number software is used and if sufficient fetal fraction is present.
Diabetic retinopathy and visual impairment in a Norwegian diabetic coast population with a high dietary intake of fish oils. An observational study
Authors: Alsbirk Knud Erik , Seland Johan Harald , Assmus Jörg
Published: September 2021

Purpose

To present retinal and visual findings in a Norwegian west coast diabetic population and to elucidate the effect of dietary intake of marine polyunsaturated fatty acids (PUFAs) on the development of diabetic retinopathy (DR).

Methods

In an eye practice in an archipelago of 314 km², serving a population of about 40 000, we recorded the prevalence of visual impairment and DR in a referred diabetic population. 510 consecutive patients were included, 238 females and 272 males. 50 patients had type I and 460 had type II diabetes mellitus (DM). Self‐reported medication, diet supplements, HbA1c and fish consumption were registered.

Results

In the type I group, the median age was 44.5 and median DM duration 11.5 years [1–44]. 48% had photographic evidence of DR, 8 patients (16%) had proliferative retinopathy (PDR), and 6 patients (12%) had diabetic macular oedema (DME). All had best‐corrected visual acuity (BCVA) of 0.5 (log MAR 0.3) or better in the best eye. In the type II group, the median DM duration was 8 years [1–53], and median age was 66. 98% had best eye BCVA at or better than 0.5 (log MAR 0.3) in the best eye.

Conclusion

None of the 510 patients had BCVA worse than 0.3 (log MAR 0.48) due to diabetic retinopathy. Compared to similar studies, we found a very low visual impairment rate. A possible protective effect of PUFA on the prevalence and progression of diabetic microangiopathy including retinopathy is discussed.
Oxygen for the delivery room respiratory support of moderate‐to‐late preterm infants. An international survey of clinical practice from 21 countries
Authors: Sotiropoulos James X. , Kapadia Vishal , Vento Maximo , Rabi Yacov , Saugstad Ola D. , Kumar R. Kishore , Schmölzer Georg M. , Zhang Huyan , Yuan Yuan , Lim Gina , Kusuda Satoshi , Arimitsu Takeshi , Nguyen Tinh Thu , Kitsommart Ratchada , Yeo Kee Thai , Oei Ju Lee
Published: September 2021

Aim

The aim of this study was to determine clinician opinion regarding oxygen management in moderate‐late preterm resuscitation.

Methods

An anonymous online questionnaire was distributed through email/social messaging platforms to neonatologists in 21 countries (October 2020‐March 2021) via REDCap.

Results

Of the 695 respondents, 69% had access to oxygen blenders and 90% had pulse oximeters. Respondents from high‐income countries were more likely to have oxygen blenders than those from middle‐income countries (72% vs. 66%). Most initiated respiratory support with FiO2 0.21 (43%) or 0.3 (36%) but only 45% titrated FiO2 to target SpO2. Most (89%) considered heart rate as a more important indicator of response than SpO2. Almost all (96%) supported the need for well‐designed trials to examine oxygenation in moderate‐late preterm resuscitation.

Conclusion

Most clinicians resuscitated moderate‐late preterm infants with lower initial FiO2 but some cannot/will not target SpO2 or titrate FiO2. Most consider heart rate as a more important indicator of infant response than SpO2.Large and robust clinical trials examining oxygen use for moderate‐late preterm resuscitation, including long‐term neurodevelopmental outcomes, are supported amongst clinicians.
Review Article: vaccination for patients with inflammatory bowel disease during the COVID‐19 pandemic
Authors: Doherty Jayne , Fennessy Sean , Stack Roisin , O’ Morain Neil , Cullen Garret , Ryan Elizabeth J. , De Gascun Cillian , Doherty Glen A.
Published: September 2021

Background

Poor immune responses are frequently observed in patients with inflammatory bowel disease (IBD) receiving established vaccines; risk factors include immunosuppressants and active disease.

Aims

To summarise available information regarding immune responses achieved in patients with IBD receiving established vaccines. Using this information, to identify risk factors in the IBD population related to poor vaccine‐induced immunity that may be applicable to vaccines against COVID‐19.

Methods

We undertook a literature review on immunity to currently recommended vaccines for patients with IBD and to COVID‐19 vaccines and summarised the relevant literature.

Results

Patients with IBD have reduced immune responses following vaccination compared to the general population. Factors including the use of immunomodulators and anti‐TNF agents reduce response rates. Patients with IBD should be vaccinated against COVID‐19 at the earliest opportunity as recommended by International Advisory Committees, and vaccination should not be deferred because a patient is receiving immune‐modifying therapies. Antibody titres to COVID‐19 vaccines appear to be reduced in patients receiving anti‐TNF therapy, especially in combination with immunomodulators after one vaccination. Therefore, we should optimise any established risk factors that could impact response to vaccination in patients with IBD before vaccination.

Conclusions

Ideally, patients with IBD should be vaccinated at the earliest opportunity against COVID‐19. Patients should be in remission and, if possible, have their corticosteroid dose minimised before vaccination. Further research is required to determine the impact of different biologics on vaccine response to COVID‐19 and the potential for booster vaccines or heterologous prime‐boost vaccinations in the IBD population.
Vedolizumab clearance in neonates, susceptibility to infections and developmental milestones: a prospective multicentre population‐based cohort study
Authors: Julsgaard Mette , Baumgart Daniel C. , Baunwall Simon M. D. , Hansen Mette M. , Grosen Anne , Bibby Bo M. , Uldbjerg Niels , Kjeldsen Jens , Sørensen Heidi G. , Larsen Lone , Wildt Signe , Weimers Petra , Haderslev Kent V. , Vind Ida , Svenningsen Lise , Brynskov Jørn , Lyhne Søren , Vestergaard Thea , Hvas Christian L. , Kelsen Jens ,   for the NOVA Study Group
Published: September 2021

Background

Little is known about the consequences of intrauterine exposure to, and the post‐natal clearance of, vedolizumab.

Aims

To investigate the levels of vedolizumab in umbilical cord blood of newborns and rates of clearance after birth, as well as how these correlated with maternal drug levels, risk of infection and developmental milestones during the first year of life

Methods

Vedolizumab‐treated pregnant women with inflammatory bowel disease were prospectively recruited from 12 hospitals in Denmark and Canada in 2016‐2020. Demographics were collected from medical records. Infant developmental milestones were evaluated by the Ages and Stages Questionnaire (ASQ‐3). Vedolizumab levels were measured at delivery and, in infants, every third month until clearance. Non‐linear regression analysis was applied to estimate clearance.

Results

In 50 vedolizumab‐exposed pregnancies, we observed 43 (86%) live births, seven (14%) miscarriages, no congenital malformations and low risk of adverse pregnancy outcomes. Median infant:mother vedolizumab ratio at birth was 0.44 (95% confidence interval [CI], 0.32‐0.56). The mean time to vedolizumab clearance in infants was 3.8 months (95% CI, 3.1‐4.4). No infant had detectable levels of vedolizumab at 6 months of age. Developmental milestones at 12 months were normal or above average. Neither vedolizumab exposure in the third trimester (RR 0.54, 95% CI, 0.28‐1.03) nor combination therapy with thiopurines (RR 1.29, 95% CI, 0.60‐2.77) seemed to increase the risk of infections in the offspring.

Conclusions

Neonatal vedolizumab clearance following intrauterine exposure is rapid. Infant vedolizumab levels did not correlate with the risk of infections during the first year of life. Continuation of vedolizumab throughout pregnancy is safe.
Targeting of cancer cell death mechanisms by curcumin: Implications to cancer therapy
Authors: Yu Chong , Yang Bo , Najafi Masoud
Published: September 2021

Cancer is known as a second major cause of death globally. Nowadays, several modalities have been developed for the treatment of cancer. Radiotherapy and chemotherapy are the most common modalities in most countries. However, newer modalities such as immunotherapy and targeted therapy drugs can kill cancer cells with minimal side effects. All anticancer agents work based on the killing of cancer cells. Numerous studies are ongoing to kill cancer cells more effectively without increasing side effects to normal tissues. The combination modalities with low toxic agents are interesting for this aim. Curcumin is one of the most common herbal agents that has shown several anticancer properties. It can regulate immune system responses against cancer. Furthermore, curcumin has been shown to potentiate cell death signalling pathways and attenuate survival signalling pathways in cancer cells. The knowledge of how curcumin induces cell death in cancers can improve therapeutic efficiency. In this review, the regulatory effects of curcumin on different cell death mechanisms and their signalling pathways will be discussed. Furthermore, we explain how curcumin may potentiate the anticancer effects of other drugs or radiotherapy through modulation of apoptosis, mitotic catastrophe, senescence, autophagy and ferroptosis.
The evolving status of immunotherapies in multiple myeloma: the future role of bispecific antibodies
Authors: Swan Dawn , Routledge David , Harrison Simon
Published: September 2021

Treatment outcomes in multiple myeloma (MM) have improved dramatically over the past 10 years. However, patients with high‐risk disease such as those with Stage III disease by the Revised International Staging System, the presence of adverse cytogenetics, or who are refractory to proteosome inhibitors, immunomodulatory drugs and monoclonal antibodies may have dismal outcomes. These patients represent an urgent ongoing need in MM. One of the hallmarks of MM is immune dysfunction and a tumour‐permissive immune microenvironment. Ameliorating the immune‐paresis could lead to improved outcomes. The role of immunotherapies has been growing at an exponential pace with numerous agents under development in clinical trials. In the present review, we provide an overview of immunotherapies in MM, focussing on bispecific antibodies (BsAbs). We review efficacy outcomes from the published clinical trials and consider the important safety aspects of these therapies, in particular the risk of cytokine‐release syndrome and immune effector cell‐associated neurotoxicity syndrome, and how these compare with patients receiving chimeric antigen receptor T cells. We discuss the MM epitopes being targeted by BsAbs, either in clinical or preclinical stages, and we consider where these therapies might best fit within the future ever‐changing paradigm of MM treatment.
Last Glacial central Mediterranean hydrology inferred from Lake Trasimeno’s (Italy) calcium carbonate geochemistry
Authors: Francke Alexander , Lacey Jack H. , Marchegiano Marta , Wagner Bernd , Ariztegui Daniel , Zanchetta Giovanni , Kusch Stephanie , Ufer Kristian , Baneschi Ilaria , Knödgen Katharina
Published: September 2021

There is still a paucity of hydrological data explaining the relationship between (rapid, millennial‐scale) climate forcing and Mediterranean rainfall since the Last Glacial. We show that distinct lake‐level fluctuations at Lake Trasimeno (Italy) are associated with changing aridity in the central Mediterranean during the last ~47 800 years. The lake‐level fluctuations are reconstructed based on carbonate mineral content and carbonate mineral species, as well as the stable oxygen and carbon isotope (δ18O and δ13C) geochemistry of endogenic carbonates. Low lake levels are linked to high carbonate, Mg‐calcite and aragonite contents, and high δ18O and δ13C values. Inferred hydrological changes are linked to glacial–interglacial and, tentatively within the limitations of our chronology, to millennial‐scale climate variability as well as the intensity of the Atlantic Meridional Overturning Circulation (AMOC). Prior to the Last Glacial Maximum (LGM), during intervals equivalent to Marine Isotope Stage 3 (MIS 3), a stronger AMOC associated with Greenland interstadial periods (Dansgaard/Oeschger (D/O) warm periods) and stronger Asian monsoon probably coincide with increased precipitation in central Italy as inferred from high lake levels at Lake Trasimeno. Periods of weak AMOC intensity such as during Greenland stadials (D/O cold periods), during Heinrich events, and weak Asian monsoons are correlated with lake level lowstands, which imply relatively dry conditions in central Italy. Lake Trasimeno’s water level during the LGM and the Lateglacial (MIS 2) is relatively stable, with recorded changes showing distinct similarities to orbital configurations. Although muted, high latitude climate forcing is still evident in the data during peak glacial conditions. The transition from D/O‐like hydrological variability at Lake Trasimeno during MIS 3 to orbitally controlled fluctuations during the Lateglacial to Holocene transition coincides with an increasing amplitude in local winter and summer insolation, probably indicating increasing seasonality and a larger temperature gradient between low‐ and high‐latitude settings.
Striving for Happily Ever After: Supportive Interventions for Youth Leaving Residential Placement. A Systematic Review of Reviews
Authors: Kvamme Line Solheim , Waaler Pamela , Helland Siri Saugestad , Kjøbli John
Published: September 2021

Background

Youth who reenter communities after forensic or residential care are overrepresented in prevalence rates for mental disorders, delinquency, incarceration, low academic achievement, and unemployment. Supportive interventions that aid youth in the reentry to their communities can be crucial for successful reintegration. In systematic reviews (SR) on this topic, only specific interventions or programs are described. Therefore, a summary of evidence about transitional interventions for various groups of reentry youth is needed.

Method

This overview of SRs was preregistered in PROSPERO. We searched PsycINFO, Ovid MEDLINE, Cochrane Library, Campbell Library, Web of Science, Sociological Abstracts, Criminal Justice Abstracts, Social Care Online, and Epistemonikos. SRs that fit the search criteria were evaluated using the AMSTAR checklist for methodological quality and the GRADE tool for assessing confidence in effect estimates.

Results

We screened 2,349 publications for eligibility. Eight SRs were included for analysis. The methodological quality of five SRs was critically low, two were of low quality, and one was of moderate quality. Recidivism was reported as the only outcome in five SRs. Detrimental outcomes were reported in five SRs. Confidence in effect estimates was low or very low for all outcomes. Ninety‐five percent of primary study populations were from the United States.

Conclusion

We offer a rigorous appraisal of SRs on transitional interventions. The gaps of knowledge are vast regarding what works, how it works, and for whom. Development of a knowledge base should include defining the term ‘recidivism’, systematic reporting of demographics, and identifying effective common elements.
Motivational psychology and the call to professional public service in Canada
Authors: Paul Brown M. , White Jonny
Published: September 2021

This article explores the phenomenon of the call to professional public service in Canada. It draws on the testimonials of exemplars in Canada and elsewhere, and research findings from the fields of prosocial behaviour and public service motivation (PSM), and especially from motivational psychology, with its concepts of “flow” and “element,” to shed light on the dynamics of the call and steps professional public services can take to best mobilize individuals responding to it. The conclusion suggests there should be greater acknowledgement of the reality of the call, embeds the call in PSM theory, and sets out an agenda for research.
The utility of radiolabeled PSMA ligands for tumor imaging
Authors: Shahrokhi Pejman , Masteri Farahani Arezou , Tamaddondar Mohammad , Rezazadeh Farzaneh
Published: September 2021

Prostate‐specific membrane antigen (PSMA) is a glycosylated type‐II transmembrane protein expressed in prostatic tissue and significantly overexpressed in several prostate cancer cells. Despite its name, PSMA has also been reported to be overexpressed in endothelial cells of benign and malignant non‐prostate disease. So its clinical use was extended to detection, staging, and therapy of various tumor types. Recently small molecules targeting PSMA have been developed as imaging probes for diagnosis of several malignancies. Preliminary studies are emerging improved diagnostic sensitivity and specificity of PSMA imaging, leading to a change in patient management. In this review, we evaluated the first preclinical and clinical studies on PSMA ligands resulting future perspectives radiolabeled PSMA in staging and molecular characterization, based on histopathologic examinations of PSMA expression.
Dynamics of circulating dendritic cells and cytokines after kidney transplantation—No effect of remote ischaemic conditioning
Authors: Nielsen Marie B , Ravlo Kristian , Eijken Marco , Krogstrup Nicoline V , Bue Svendsen Morten , Abdel-Halim Chadi , Steen Petersen Mikkel , Birn Henrik , Oltean Mihai , Jespersen Bente , Møller Bjarne K
Published: September 2021

Inflammation resulting from ischaemia/reperfusion injury can cause kidney graft dysfunction, increase the risk of delayed graft function and possibly reduce long-term graft survival. Remote ischaemic conditioning may protect against ischaemia/reperfusion injury and mitigate the immunological response to the graft. We investigated the immunological effects of remote ischaemic conditioning on kidney transplantation from deceased donors in the randomized CONTEXT study. Three circulating dendritic cell (DC) subtypes identified in peripheral blood from kidney transplant recipients [myeloid DCs, plasmacytoid DCs and immunoglobulin-like transcript (ILT)3+ DCs] were measured at baseline, days 1, 3 and 5 and 1 and 3 months after transplantation. We also quantified 21 cytokines at baseline, days 1 and 5 and 3 months after transplantation. Neither DC counts nor cytokine levels differed between patients receiving remote ischaemic conditioning and controls; however, several parameters exhibited dynamic and parallel alterations in the two groups over time, reflecting the immunological response to the kidney transplantation and immunosuppression.
Improvement in immune dysfunction after FOLFOX chemotherapy for Stage III colon cancer is associated with improved minimal residual disease prognostic subtype and outcome
Authors: Murray Nigel P. , Villalon Ricardo , Hartmann Dan , Rodriguez Maria Patricia , Aedo Socrates
Published: September 2021

Aim

Minimal residual disease (MRD) is the net result of the biological properties of disseminated tumour cells and the effect of the immune system and treatment to eliminate them. The aim of this work is to report the changes in MRD status and immune function (lymphocyte count) after FOLFOX chemotherapy, and the outcome in Stage III colon cancer patients.

Method

This study is a prospective, single‐centre observational study. Lymphocyte counts were determined prior to and 1, 2 and 3 months after the completion of chemotherapy. Circulating tumour cells (CTCs) and bone marrow micrometastases were determined using immunocytochemistry with anticarcinoembryonic antigen prior to and 1 month after chemotherapy. MRD was classified as negative (Group I), micrometastasis positive only (Group II) and CTC positive (Group III). Changes in lymphocyte counts and MRD subtype following chemotherapy and relapse‐free progression were analysed.

Results

Of the total of 185 patients, 83 (44.9%) relapsed. The risk of relapse significantly increased from Groups I to III (p < 0.001) and with decreasing lymphocyte count (p < 0.01). The lymphocyte count significantly decreased from Groups I to III (p < 0.001). Multivariance Cox regression analysis showed hazard ratios of 3.58 (Group II), 17.43 (Group III) and 0.39 (lymphocyte count) in predicting relapse. Following chemotherapy, improved lymphocyte count was associated with improved MRD subtype (p < 0.0001). Neither baseline lymphocyte count nor MRD subtype predicted response to chemotherapy. Five‐year relapse‐free survival for combined lymphocyte–MRD subtypes was 95%, 57% and 5% for Groups I to III, respectively (p < 0.001).

Conclusion

Following chemotherapy, improvements in immune function were associated with improved MRD subtype and a better relapse‐free survival.
Rerouting a major Indonesian mining road to spare nature and reduce development costs
Authors: Engert Jayden E. , Ishida F‪rançoise Yoko , Laurance William F.
Published: September 2021

Road‐infrastructure projects are expanding rapidly worldwide while penetrating into previously undisturbed forests. In Sumatra, Indonesia, a planned 88‐km‐long mining road for transporting coal would imperil the Harapan Forest, the island's largest surviving tract of lowland rainforest. Such roads often lead to increased forest encroachment and illegal logging, fires, poaching, and mining. To evaluate the potential impact of the proposed road, we first manually mapped all existing roads inside and around the Harapan Forest using remote‐sensing imagery. We then calculated the expected increase in forest loss from three proposed mining‐road routes using a metric based on travel‐time mapping. Finally, we used least‐cost‐path analyses to identify new routes for the road that would minimize forest disruption and road‐construction costs. We found that road density inside and nearby the Harapan Forest is already 3–4 times higher than official data sources indicate. Based on our analyses, each of the three proposed mining‐road routes would lead to 3,000–4,300 ha of additional forest loss from human encroachment plus another 424 ha lost from road construction itself. We propose new routes for the mining road that would result in up to 3,321 ha less forest loss with markedly lower construction costs than any other planned route. We recommend approaches such as ours, using least‐cost‐path analysis, to minimize the environmental and financial costs of major development projects.
Dimensions of Curation Competing Values Model: Tool for Shifting Exhibition Priorities in Art Museums
Authors: Rowson Love Ann , Villeneuve Pat , Burns James , Wessel Brooke , Jiang Xiaonan
Published: September 2021

In this article we present the Dimensions of Curation Competing Values Model for exhibition curation. It is based on the work of Quinn and Rohrbaugh (1981), scholars who abandoned their quest for a universal model for organizational effectiveness when confronted with literature advocating alternate positions, such as whether an organization should look inward or focus outward to be effective. They acknowledged that any of these “recognized dilemmas” (p. 132) could produce organizational effectiveness depending on context. They conceptualized these seemingly contradictory positions as competing values and offered a 3‐dimensional model with the alternatives, along with a range of practices in between, arrayed along continua. We saw similarities with on‐going competing debates in the museum world, such as whether exhibitions should focus on objects or audiences, and adapted their model specifically for exhibition curation. Based on theory, literature, and field practices, Dimensions of Curation addresses ranges of possible interpretive focus, curatorial power, and curatorial intent. We demonstrate various combinations of the resulting eight exhibition models that we label descriptively as exhibitions that ____, with each model achieving different objectives and audience appeal. We envision Dimensions of Curation as a tool for practitioners to use to reflect on past exhibition practices, think intentionally about future exhibitions, and make changes, as desired, using the model as a road map. It also provides a shared vocabulary of practice for the field, as advocated by Carr (2007).
Cerebral palsy and epilepsy: a health informatics approach
Authors: Chin Richard F
Published: September 2021

This commentary is on the original article by Szpindel et al. on pages 259–265 of this issue.
HbA1c combined with glycated albumin or 1,5‐anhydroglucitol improves the efficiency of diabetes screening in a Chinese population
Authors: Qian Junyi , Chen Cheng , Wang Xiaohang , Tan Yuanyuan , Yang Jiao , Yuan Yuexing , Chen Juan , Guo Haijian , Wang Bei , Sun Zilin , Wang Yao
Published: September 2021

Aims

This study aimed to evaluate the ability of HbA1c combined with glycated albumin (GA) or 1,5‐anhydroglucitol (1,5‐AG) to detect diabetes in residents of Jiangsu, China.

Methods

The oral glucose tolerance test (OGTT) was performed on 2184 people in Jiangsu. HbA1c, GA, 1,5‐AG and other serum biochemical parameters were measured. Receiver operating characteristic curves were plotted to determine the optimal thresholds of HbA1c, GA and 1,5‐AG according to the Youden index.

Results

(1) The optimal thresholds of HbA1c, GA and 1,5‐AG for the screening of diabetes were ≥45 mmol/mol (6.3%), ≥13.0% and ≤23.0 μg/ml, respectively. (2) The sensitivities of HbA1c combined with GA and 1,5‐AG were both 85%, higher than that of HbA1c (70%, p < 0.001).

Conclusions

This study is suitable for cases where plasma glucose is unavailable. Among the residents of Jiangsu, HbA1c combined with GA or 1,5‐AG can improve the sensitivity of diabetes screening, reduce the miss rate and save the use of OGTT. GA and 1,5‐AG are superior in individuals with mild glucose metabolism disorder. GA enhances the detection of diabetes in the nonobese, and 1,5‐AG enhances the detection in those with hyperuricaemia.