bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a wearable consumer noise measurement device in a laboratory setting
Authors: Roberts Benjamin , Jacobs Neva , Mathis Claire , Reamer Heidi , Kardous Chucri (Chuck) , Gaffney Shannon , L. Neitzel Richard
Published: July 2022

Exposure to noise occurs throughout daily life and, depending on the intensity, duration, and context, can lead to hearing loss, disturbed sleep, decreased academic achievement, and other negative health outcomes. Recently, smartwatches that use the device's onboard microphone to measure noise levels were released. This study evaluated the accuracy of these smartwatches in a controlled laboratory setting. For broadband pink noise, a total of 11 441 measurements were collected. The results showed that, on average, the smartwatch reported 3.4 dBA lower than the reference system on average. For the octave-band, a total of 18 449 measurements were collected. The smartwatch measured lower than the reference microphone from the 125 Hz to 1000 Hz octave bands, were somewhat in agreement at 2000 Hz, measured higher sound pressure levels than the reference microphone at 4000 Hz, and then lower at 8000 Hz. Despite not meeting the ANSI criteria for sound level meters, in some cases, these smartwatches still provide a reasonable degree of accuracy and have the potential for use in studies that require the measurement of personal noise exposure over an extended period.
Associations of Device-Measured Physical Activity, Sedentary Behavior, and Executive Function in Preadolescents: A Latent Profile Approach
Authors: Zhu Yuxin , Sun Fenghua , Chow Gary C.C. , Tao Sisi , Cooper Simon B. , Zhang Borui , Wong Thomson W.L.
Published: July 2022

Purpose: This study investigated the associations between physical activity (PA), sedentary behavior, and executive function in preadolescents. Methods: One hundred and twenty preadolescents were recruited from 2 Hong Kong primary schools. PA and sedentary behavior were recorded for 7 consecutive days by accelerometer. Executive function performance, including inhibition (Stroop task and Flanker task) and working memory (Sternberg paradigm task), were measured. Body mass index and cardiorespiratory fitness (multistage fitness test) were tested. Latent profile analysis explored the profiles of PA and sedentary behavior in preadolescents. Results: Three distinct profiles were identified: low activity, average activity, and high activity. Participants in low activity performed worse in the accuracy of Stroop task (vs average activity, P = .03; vs high activity, P < .01), Flanker task (vs average activity, P = .02; vs high activity, P < .001), and Sternberg paradigm task (vs average activity, P < .01; vs high activity, P < .01). No significant difference was observed between participants with average and high activities. No significant association was observed for profiles on body mass index and cardiorespiratory fitness. Conclusion: Supplementing the consensus of the literature that moderate to vigorous PA benefits cognition, the authors conclude that light PA may also enhance preadolescents’ executive functioning.
Noncanonical activation of GLI signaling in SOX2
+
cells drives medulloblastoma relapse
Authors: Swiderska-Syn Marzena , Mir-Pedrol Júlia , Oles Alexander , Schleuger Olga , Salvador April D. , Greiner Sean M. , Seward Cara , Yang Fan , Babcock Benjamin R. , Shen Chen , Wynn Daniel T. , Sanchez-Mejias Avencia , Gershon Timothy R. , Martin Vanesa , McCrea Heather J. , Lindsey Kathryn G. , Krieg Carsten , Rodriguez-Blanco Jezabel
Published: July 2022

SRY (sex determining region Y)–box 2 (SOX2)–labeled cells play key roles in chemoresistance and tumor relapse; thus, it is critical to elucidate the mechanisms propagating them. Single-cell transcriptomic analyses of the most common malignant pediatric brain tumor, medulloblastoma (MB), revealed the existence of astrocytic
Sox2
+
cells expressing sonic hedgehog (SHH) signaling biomarkers. Treatment with vismodegib, an SHH inhibitor that acts on Smoothened (Smo), led to increases in astrocyte-like

Sox2
+

cells. Using SOX2-enriched MB cultures, we observed that SOX2
+
cells required SHH signaling to propagate, and unlike in the proliferative tumor bulk, the SHH pathway was activated in these cells downstream of Smo in an MYC-dependent manner. Functionally different GLI inhibitors depleted vismodegib-resistant SOX2
+
cells from MB tissues, reduced their ability to further engraft in vivo, and increased symptom-free survival. Our results emphasize the promise of therapies targeting GLI to deplete SOX2
+
cells and provide stable tumor remission.
Microrobotic swarms for selective embolization
Authors: Law Junhui , Wang Xian , Luo Mengxi , Xin Liming , Du Xingzhou , Dou Wenkun , Wang Tiancong , Shan Guanqiao , Wang Yibin , Song Peng , Huang Xi , Yu Jiangfan , Sun Yu
Published: July 2022

Inspired by the collective intelligence in natural swarms, microrobotic agents have been controlled to form artificial swarms for targeted drug delivery, enhanced imaging, and hyperthermia. Different from these well-investigated tasks, this work aims to develop microrobotic swarms for embolization, which is a clinical technique used to block blood vessels for treating tumors, fistulas, and arteriovenous malformations. Magnetic particle swarms were formed for selective embolization to address the low selectivity of the present embolization technique that is prone to cause complications such as stroke and blindness. We established an analytical model that describes the relationships between fluid viscosity, flow rate, branching angle, magnetic field strength, and swarm integrity, based on which an actuation strategy was developed to maintain the swarm integrity inside a targeted region under fluidic flow conditions. Experiments in microfluidic channels, ex vivo tissues, and in vivo porcine kidneys validated the efficacy of the proposed strategy for selective embolization.
Imaging mesoscopic antiferromagnetic spin textures in the dilute limit from single-geometry resonant coherent x-ray diffraction
Authors: Bluschke Martin , Basak Rourav , Barbour Andi , Warner Ashley N. , Fürsich Katrin , Wilkins Stuart , Roy Sujoy , Lee James , Christiani Georg , Logvenov Gennady , Minola Matteo , Keimer Bernhard , Mazzoli Claudio , Benckiser Eva , Frano Alex
Published: July 2022

The detection and manipulation of antiferromagnetic domains and topological antiferromagnetic textures are of central interest to solid-state physics. A fundamental step is identifying tools to probe the mesoscopic texture of an antiferromagnetic order parameter. In this work, we demonstrate that Bragg coherent diffractive imaging can be extended to study the mesoscopic texture of an antiferromagnetic order parameter using resonant magnetic x-ray scattering. We study the onset of the antiferromagnet transition in PrNiO
3
, focusing on a temperature regime in which the antiferromagnetic domains are dilute in the beam spot and the coherent diffraction pattern modulating the antiferromagnetic peak is greatly simplified. We demonstrate that it is possible to extract the arrangements and sizes of these domains from single diffraction patterns and show that the approach could be extended to a time-structured light source to study the motion of dilute domains or the motion of topological defects in an antiferromagnetic spin texture.
Knowledge overconfidence is associated with anti-consensus views on controversial scientific issues
Authors: Light Nicholas , Fernbach Philip M. , Rabb Nathaniel , Geana Mugur V. , Sloman Steven A.
Published: July 2022

Public attitudes that are in opposition to scientific consensus can be disastrous and include rejection of vaccines and opposition to climate change mitigation policies. Five studies examine the interrelationships between opposition to expert consensus on controversial scientific issues, how much people actually know about these issues, and how much they think they know. Across seven critical issues that enjoy substantial scientific consensus, as well as attitudes toward COVID-19 vaccines and mitigation measures like mask wearing and social distancing, results indicate that those with the highest levels of opposition have the lowest levels of objective knowledge but the highest levels of subjective knowledge. Implications for scientists, policymakers, and science communicators are discussed.
G6PD-mediated increase in de novo NADP
+
biosynthesis promotes antioxidant defense and tumor metastasis
Authors: Zhang Yang , Xu Yi , Lu Wenyun , Li Jinyang , Yu Sixiang , Brown Eric J. , Stanger Ben Z. , Rabinowitz Joshua D. , Yang Xiaolu
Published: July 2022

Metastasizing cancer cells are able to withstand high levels of oxidative stress through mechanisms that are poorly understood. Here, we show that under various oxidative stress conditions, pancreatic cancer cells markedly expand NADPH and NADP
+
pools. This expansion is due to up-regulation of glucose-6-phosphate dehydrogenase (G6PD), which stimulates the cytoplasmic nicotinamide adenine dinucleotide kinase (NADK1) to produce NADP
+
while converting NADP
+
to NADPH. G6PD is activated by the transcription factor TAp73, which is, in turn, regulated by two pathways. Nuclear factor–erythroid 2 p45-related factor-2 suppresses expression of the ubiquitin ligase PIRH2, stabilizing the TAp73 protein. Checkpoint kinases 1/2 and E2F1 induce expression of the
TAp73
gene. Levels of G6PD and its upstream activators are elevated in metastatic pancreatic cancer. Knocking down G6PD impedes pancreatic cancer metastasis, whereas forced G6PD expression promotes it. These findings reveal an intracellular network that maintains redox homeostasis through G6PD-mediated increase in de novo NADP
+
biosynthesis, which may be co-opted by tumor cells to enable metastasis.
Dissecting motor skill acquisition: Spatial coordinates take precedence
Authors: Maceira-Elvira Pablo , Timmermann Jan E. , Popa Traian , Schmid Anne-Christine , Krakauer John W. , Morishita Takuya , Wessel Maximilian J. , Hummel Friedhelm C.
Published: July 2022

Practicing a previously unknown motor sequence often leads to the consolidation of motor chunks, which enable its accurate execution at increasing speeds. Recent imaging studies suggest the function of these structures to be more related to the encoding, storage, and retrieval of sequences rather than their sole execution. We found that optimal motor skill acquisition prioritizes the storage of the spatial features of the sequence in memory over its rapid execution early in training, as proposed by Hikosaka in 1999. This process, seemingly diminished in older adults, was partially restored by anodal transcranial direct current stimulation over the motor cortex, as shown by a sharp improvement in accuracy and an earlier yet gradual emergence of motor chunks. These results suggest that the emergence of motor chunks is preceded by the storage of the sequence in memory but is not its direct consequence; rather, these structures depend on, and result from, motor practice.
Targeted BACE-1 inhibition in microglia enhances amyloid clearance and improved cognitive performance
Authors: Singh Neeraj , Das Brati , Zhou John , Hu Xiangyou , Yan Riqiang
Published: July 2022

Abnormal accumulation of β-amyloid (Aβ) peptides is a culprit in Alzheimer’s disease (AD); blocking Aβ generation is therefore being explored as a logical approach for AD treatment. Here, we demonstrate that targeted inhibition of β-site amyloid precursor protein (APP) cleaving enzyme-1 (BACE-1) in microglia has unique advantages. When
Bace-1
was deleted in Alzheimer’s 5xFAD microglia, fewer amyloid plaques developed, and this reduction was not due to changes in APP processing but rather to enhanced Aβ clearance, in line with the increase in a microglial gene signature favoring phagocytosis. Moreover, deletion of
Bace-1
in microglia enhances functions of autophagolysosomes and Aβ-induced metabolic reprogramming necessary for Aβ degradation by favoring phosphorylation of mammalian target of rapamycin complex (mTOR) at Ser
2448
and modulating the PI3K–mTOR–HIF-1α signaling pathways. Mice with deletion of
Bace-1
in microglia showed no reduction in long-term potentiation, unlike global deletion of
Bace-1
. Our results suggest that targeted inhibition of BACE-1 in microglia is a superior strategy for AD treatment.
Circularity in mixed-plastic chemical recycling enabled by variable rates of polydiketoenamine hydrolysis
Authors: Demarteau Jeremy , Epstein Alexander R. , Christensen Peter R. , Abubekerov Mark , Wang Hai , Teat Simon J. , Seguin Trevor J. , Chan Christopher W. , Scown Corinne D. , Russell Thomas P. , Keasling Jay D. , Persson Kristin A. , Helms Brett A.
Published: July 2022

Footwear, carpet, automotive interiors, and multilayer packaging are examples of products manufactured from several types of polymers whose inextricability poses substantial challenges for recycling at the end of life. Here, we show that chemical circularity in mixed-polymer recycling becomes possible by controlling the rates of depolymerization of polydiketoenamines (PDK) over several orders of magnitude through molecular engineering. Stepwise deconstruction of mixed-PDK composites, laminates, and assemblies is chemospecific, allowing a prescribed subset of monomers, fillers, and additives to be recovered under pristine condition at each stage of the recycling process. We provide a theoretical framework to understand PDK depolymerization via acid-catalyzed hydrolysis and experimentally validate trends predicted for the rate-limiting step. The control achieved by PDK resins in managing chemical and material entropy points to wide-ranging opportunities for pairing circular design with sustainable manufacturing.
Rescue of autosomal dominant hearing loss by in vivo delivery of mini dCas13X-derived RNA base editor
Authors: Xiao Qingquan , Xu Zhijiao , Xue Yuanyuan , Xu Chunlong , Han Lei , Liu Yuanhua , Wang Fang , Zhang Runze , Han Shuang , Wang Xing , Li Geng-Lin , Li Huawei , Yang Hui , Shu Yilai
Published: July 2022

Programmable RNA editing tools enable the reversible correction of mutant transcripts, reducing the potential risk associated with permanent genetic changes associated with the use of DNA editing tools. However, the potential of these RNA tools to treat disease remains unknown. Here, we evaluated RNA correction therapy with Cas13-based RNA base editors in the myosin VI p.C442Y heterozygous mutation (
Myo6
C442Y/+
) mouse model that recapitulated the phenotypes of human dominant-inherited deafness. We first screened several variants of Cas13-based RNA base editors and guide RNAs (gRNAs) targeting
Myo6
C442Y
in cultured cells and found that mini dCas13X.1-based adenosine base editor (mxABE), composed of truncated Cas13X.1 and the RNA editing enzyme adenosine deaminase acting on RNA 2 deaminase domain variant (ADAR2dd
E488Q
), exhibited both high efficiency of A > G conversion and low frequency of off-target edits. Single adeno-associated virus (AAV)–mediated delivery of mxABE in the cochlea corrected the mutated
Myo6
C442Y
to
Myo6
WT
allele in homozygous
Myo6
C442Y/C442Y
mice and resulted in increased
Myo6
WT
allele in the injected cochlea of
Myo6
C442Y/+
mice. The treatment rescued auditory function, including auditory brainstem response and distortion product otoacoustic emission up to 3 months after AAV-mxABE-
Myo6
injection in
Myo6
C442Y/+
mice. We also observed increased survival rate of hair cells and decreased degeneration of hair bundle morphology in the treated compared to untreated control ears. These findings provide a proof-of-concept study for RNA editing tools as a therapeutic treatment for various semidominant forms of hearing loss and other diseases.
Intranasal vaccination with lipid-conjugated immunogens promotes antigen transmucosal uptake to drive mucosal and systemic immunity
Authors: Hartwell Brittany L. , Melo Mariane B. , Xiao Peng , Lemnios Ashley A. , Li Na , Chang Jason Y.H. , Yu Jingyou , Gebre Makda S. , Chang Aiquan , Maiorino Laura , Carter Crystal , Moyer Tyson J. , Dalvie Neil C. , Rodriguez-Aponte Sergio A. , Rodrigues Kristen A. , Silva Murillo , Suh Heikyung , Adams Josetta , Fontenot Jane , Love J. Christopher , Barouch Dan H. , Villinger Francois , Ruprecht Ruth M. , Irvine Darrell J.
Published: July 2022

To combat the HIV epidemic and emerging threats such as SARS-CoV-2, immunization strategies are needed that elicit protection at mucosal portals of pathogen entry. Immunization directly through airway surfaces is effective in driving mucosal immunity, but poor vaccine uptake across the mucus and epithelial lining is a limitation. The major blood protein albumin is constitutively transcytosed bidirectionally across the airway epithelium through interactions with neonatal Fc receptors (FcRn). Exploiting this biology, here, we demonstrate a strategy of “albumin hitchhiking” to promote mucosal immunity using an intranasal vaccine consisting of protein immunogens modified with an amphiphilic albumin-binding polymer-lipid tail, forming amph-proteins. Amph-proteins persisted in the nasal mucosa of mice and nonhuman primates and exhibited increased uptake into the tissue in an FcRn-dependent manner, leading to enhanced germinal center responses in nasal-associated lymphoid tissue. Intranasal immunization with amph-conjugated HIV Env gp120 or SARS-CoV-2 receptor binding domain (RBD) proteins elicited 100- to 1000-fold higher antigen-specific IgG and IgA titers in the serum, upper and lower respiratory mucosa, and distal genitourinary mucosae of mice compared to unmodified protein. Amph-RBD immunization induced high titers of SARS-CoV-2–neutralizing antibodies in serum, nasal washes, and bronchoalveolar lavage. Furthermore, intranasal amph-protein immunization in rhesus macaques elicited 10-fold higher antigen-specific IgG and IgA responses in the serum and nasal mucosa compared to unmodified protein, supporting the translational potential of this approach. These results suggest that using amph-protein vaccines to deliver antigen across mucosal epithelia is a promising strategy to promote mucosal immunity against HIV, SARS-CoV-2, and other infectious diseases.
A hitchhiker’s guide to mucosal and systemic immunity
Authors: Szoka Francis C.
Published: July 2022

PEGylated lipid protein immunogens delivered intranasally to mice and macaques drive production of IgG and IgA antibodies at other mucosal sites (Hartwell
et al.
).
Triazole Priming as an Adaptive Response and Gateway to Resistance in Aspergillus fumigatus
Authors: Harish Ety , Sarkar Argha , Handelman Mariana , Abo Kandil Amar , Shadkchan Yana , Wurster Sebastian , Kontoyiannis Dimitrios P. , Osherov Nir
Published: July 2022

Invasive aspergillosis (IA), caused predominantly by
Aspergillus fumigatus
, is the most common opportunistic mold infection in immunocompromised patients. Resistance of
A. fumigatus
to triazoles has been increasingly reported, leading to poor outcomes of IA to the front-line azoles.
Characterization of Functional B-Cell Epitopes at the Amino Terminus of
Shigella
Invasion Plasmid Antigen B (IpaB)
Authors: Li Siqi , Han Xinfeng , Upadhyay Ipshita , Zhang Weiping
Published: July 2022

Currently, there are no effective measures for control or prevention of
Shigella
infection, the most common cause of diarrhea in children 3 to 5 years of age in developing countries. Challenges in developing
Shigella
vaccines include virulence heterogeneity among species and serotypes.
Multiomic Analyses Reveal the Effects of Supplementing Phytosterols on the Metabolic Function of the Rumen Microbiota in Perinatal Cows
Authors: Lv Donghai , Gao Jian , Wu Zichen , Sun Zhanying , Hao Lizhuang , Liu Suozhu , Tan Zhankun , Cheng Yanfen , Zhu Weiyun
Published: July 2022

Perinatal cows suffer serious physiological stress and energy deficiency. Phytosterols have bioactive functions for gut microbes.
Interplay between Sulfur Assimilation and Biodesulfurization Activity in Rhodococcus qingshengii IGTS8: Insights into a Regulatory Role of the Reverse Transsulfuration Pathway
Authors: Martzoukou Olga , Glekas Panayiotis D. , Avgeris Margaritis , Mamma Diomi , Scorilas Andreas , Kekos Dimitris , Amillis Sotiris , Hatzinikolaou Dimitris G.
Published: July 2022

Precise genome editing of the model biocatalyst
Rhodococcus qingshengii
IGTS8 was performed for the first time, more than 3 decades after its initial discovery. We thus gained insight into the regulation of
dsz
gene expression and biocatalyst activity, depending on the presence of two reverse transsulfuration enzymes, CβS and MetB.
The Gut Bacterial Community Potentiates Clostridioides difficile Infection Severity
Authors: Lesniak Nicholas A. , Schubert Alyxandria M. , Flynn Kaitlin J. , Leslie Jhansi L. , Sinani Hamide , Bergin Ingrid L. , Young Vincent B. , Schloss Patrick D.
Published: July 2022

Clostridioides difficile
colonization can be asymptomatic or develop into an infection ranging in severity from mild diarrhea to toxic megacolon, sepsis, and death. Models that predict severity and guide treatment decisions are based on clinical factors and
C. difficile
characteristics.
Multiple Photolyases Protect the Marine Cyanobacterium
Synechococcus
from Ultraviolet Radiation
Authors: Haney Allissa M. , Sanfilippo Joseph E. , Garczarek Laurence , Partensky Frédéric , Kehoe David M.
Published: July 2022

Cells use DNA photolyases to protect their DNA from the damaging effects of UV radiation. Marine cyanobacteria possess many genes that appear to encode photolyases, but the function of the proteins encoded by these genes is unclear.
Impaired Succinate Oxidation Prevents Growth and Influences Drug Susceptibility in Mycobacterium tuberculosis
Authors: Adolph Cara , McNeil Matthew B. , Cook Gregory M.
Published: July 2022

New drugs are urgently required to combat the tuberculosis epidemic that claims 1.5 million lives annually. Inhibitors of mycobacterial energy metabolism have shown significant promise clinically; however, further advancing this nascent target space requires a more fundamental understanding of the respiratory enzymes and pathways used by
Mycobacterium tuberculosis
.
Phage-Encoded Sigma Factors Alter Bacterial Dormancy
Authors: Schwartz D. A. , Lehmkuhl B. K. , Lennon J. T.
Published: July 2022

As obligate parasites, phages exert strong top-down pressure on host populations with eco-evolutionary implications for community dynamics and ecosystem functioning. The process of phage infection, however, is constrained by bottom-up processes that influence the energetic and nutritional status of susceptible hosts.
One-Pot Isothermal LAMP-CRISPR-Based Assay for Klebsiella pneumoniae Detection
Authors: Qiu Xiaotong , Liu Xueping , Ma Xiao , Wang Ruixue , Chen Shenglin , Li Fang , Li Zhenjun
Published: July 2022

Klebsiella pneumoniae
is a significant threat to global health. At present, the methods of
K. pneumoniae
detection are culture-based and instrument-dependent and are not suitable for rapid diagnostic.
Exploring the Transient Microbe Population on Citrus Butterfly Wings
Authors: Kamala Jayanthi P. D. , Vyas Meenal
Published: July 2022

This is a first study reporting the presence of culturable microbes on an unusual ecological niche such as butterfly wings. Our findings also establish that microbes inhabit these niches before the butterfly has contact with the environment. The findings in this report have opened up a new area of research which will not only help understand the microbiome of insect wings but might prove beneficial in other specialized studies.
The
In Vitro
Replication Cycle of Achromobacter xylosoxidans and Identification of Virulence Genes Associated with Cytotoxicity in Macrophages
Authors: Pickrum Adam M. , Riegert Molly O. , Wells Clive , Brockman Kenneth , Frank Dara W.
Published: July 2022

Patients affected by CF develop chronic bacterial infections characterized by inflammatory exacerbations and tissue damage. Advancements in sequencing technologies have broadened the list of opportunistic pathogens colonizing the CF lung.
A. xylosoxidans
is increasingly recognized as an opportunistic pathogen in CF, yet our understanding of the bacterium as a contributor to human disease is limited.
The transition from continental to lithospheric breakup recorded in proto-oceanic crust: Insights from the NW South China Sea
Authors: Chao Peng , Manatschal Gianreto , Zhang Cuimei , Chenin Pauline , Ren Jianye , Pang Xiong , Zheng Jingyun
Published: July 2022

The formation of a new plate boundary and creation of the first oceanic crust, two of the most important processes of plate tectonics, still remains little understood. While older studies used to assumed a sharp ocean-continent boundary between continent and ocean, recent studies suggest a progressive oceancontinent transition (OCT) between unequivocal continental and oceanic crusts. In the latter view, breakup is not instantaneous but a lasting phase, which raises questions about the nature of the OCT basement and the processes operating between continental and lithospheric breakup. Based on detailed observations of high-quality and yet unpublished reflection seismic data, we describe and interpret the characteristic structures of the NW-South China Sea OCT and their relationship with overlying syn-breakup phase sediments. We show that the OCT displays a transition from fault-dominated rifting to magma-dominated seafloor spreading. On its continent-ward side, the OCT is made of hybrid crust where tectonic thinning of continental crust is compensated by syn-extensional magmatic thickening. Oceanward, the hybrid crust evolves into a fully magmatic but fault-dominated proto-oceanic crust, and finally turns into a mature Penrose-type oceanic crust. Relying on the growth structures observed in the syn-breakup sedimentary sequences and magmatic additions, we propose a kinematic restoration of the breakup phase. We suggest out-of-sequence flip-flop faulting to explain the switch from asymmetrical, fault-dominated-extension, to fully magmatic and largely symmetrical syn-extension accretion recorded in the syn-breakup sedimentary sequences overlying the OCT.
Recognising immunotherapy-induced meningoencephalitis: a case during treatment for primary metastatic melanoma of the bladder neck
Authors: Grunhut Joel , Brown Shimron , Lutzky Jose , Skoczylas Leor
Published: July 2022

Although novel immunotherapy has shown promise for patients with melanoma, a more activated state of the immune system may lead to adverse systemic effects. Immunotherapy-induced meningoencephalitis is a rare and seldom reported adverse effect of immunotherapy but with the expanding role of immunotherapy in cancer treatments it must be recognised. Patients receiving immunotherapy should receive a proper warning about the potential for this life-threatening condition. Herein, we report a patient in his 70s with neurological changes after his second treatment with dual immunotherapy for a primary metastatic melanoma of the bladder neck.
Pre-excitation syndrome presenting with acute myocardial infarction
Authors: Rajendran Kapil , Thankachan Anjos , Sreedharan Mohanan Kurukkanparambil , Salam Abdul
Published: July 2022

A male in his mid 50s, chronic smoker and hypertensive for 10 years presented with history suggestive of typical angina, electrocardiographic evidence of pre-excitation and serial elevation of cardiac biomarkers. Serial electrocardiograms showed subtle changes (axis shift, horizontal ST-segment changes) that could be presumptive of an anterior wall myocardial infarction. Speckle tracking echocardiography revealed territorial reduction of longitudinal strain corresponding to the left anterior descending artery with coronary angiography corroborating the same and underwent successful revascularisation. Exercise stress testing showed abrupt and complete disappearance of delta wave and normalisation of PR interval which indicates that the patient has low risk of developing malignant arrhythmias and sudden cardiac death.
Isolated post laparoscopic DIEA injury in bilateral DIEP breast reconstruction
Authors: Pezas Theodore Paul , Saour Samer , Ali Farida
Published: July 2022

Scarring from previous open abdominal surgery in patients undergoing autologous deep inferior epigastric perforator (DIEP) breast reconstruction has been reported to increase overall flap and donor site complication rates. The evidence to date demonstrates that it can be performed safely although with significantly higher postoperative donor site morbidity. It would seem logical that minimal access laparoscopic surgery is less likely to be associated with increased risks to flap vascularity or donor-site complications; however, there is little evidence available in the literature about the impact of previous laparoscopic surgery to the DIEP harvest site. The typical positions for port placement in standard laparoscopic procedures are usually distant from ideal perforator locations reducing the risk of perforator damage. We present a case of unilateral isolated injury to the proximal deep inferior epigastric artery (DIEA) following previous laparoscopic abdominal surgery in a patient undergoing bilateral mastectomy and breast reconstruction with bilateral free DIEP flaps.
Update on the management of diabetes in long-term care facilities
Authors: Idrees Thaer , Castro-Revoredo Iris A , Migdal Alexandra L , Moreno Emmelin Marie , Umpierrez Guillermo E
Published: July 2022

The number of patients with diabetes is increasing among older adults in the USA, and it is expected to reach 26.7 million by 2050. In parallel, the percentage of older patients with diabetes in long-term care facilities (LTCFs) will also rise. Currently, the majority of LTCF residents are older adults and one-third of them have diabetes. Management of diabetes in LTCF is challenging due to multiple comorbidities and altered nutrition. Few randomized clinical trials have been conducted to determine optimal treatment for diabetes management in older adults in LTCF. The geriatric populations are at risk of hypoglycemia since the majority are treated with insulin and have different levels of functionality and nutritional needs. Effective approaches to avoid hypoglycemia should be implemented in these settings to improve outcome and reduce the economic burden. Newer medication classes might carry less risk of developing hypoglycemia along with the appropriate use of technology, such as the use of continuous glucose monitoring. Practical clinical guidelines for diabetes management including recommendations for prevention and treatment of hypoglycemia are needed to appropriately implement resources in the transition of care plans in this vulnerable population.
Medical students’ exposure to and attitudes towards product promotion and incentives from the pharmaceutical industry in 2019: a national cross-sectional study in France
Authors: Molina Martin , Boëffard Adeline , Esvan Maxime , Bastian Benjamin
Published: July 2022

Objectives

To measure medical students’ exposure to pharmaceutical product promotion and incentives nationwide, and to evaluate students’ attitudes towards the pharmaceutical industry, access to education on promotional strategies and knowledge of institutional policies about drug company-student relationships.

Design

Cross-sectional survey based on a 48-item anonymous questionnaire.

Setting

All 37 French medical schools, from March to April 2019.

Participants

French medical students in their 4th year of study and beyond, having studied exclusively in France.

Main outcome measure

Cumulative frequency of students’ exposure to pharmaceutical product promotion and incentives.

Secondary outcome measures

Exposure within the last 6 months, attitudes regarding interactions with the industry, access to education on pharmaceutical product promotion and incentives and knowledge of institutional policies.

Results

6280 responses were analysed (10.4% out of a total of 60 550 eligible students). 5992 students (96.3% poststratification, 99% CI (96.1% to 96.5%)) had already been exposed to pharmaceutical product promotion and incentives and 4650 (78.1%, 99% CI (77.7% to 78.6%)) within the last 6 months. 5140 students (85.4%, 99% CI (84.8% to 85.8%)) had met a pharmaceutical representative. Regarding attitudes, 2195 students (36.8%, 99% CI (36.0% to 37.5%)) thought receiving a gift could influence their own prescriptions while 3252 (53.6%, 99% CI (53.1% to 54.2%)) thought it could influence their colleagues’ prescriptions. 4533 students (76.0%, 99% CI (75.6% to 76.5%)) reported never having attended any lecture on promotional strategies. Exposure seemed to depend on the year of study and specialty. 5122 (88.1%, 99% CI (87.7% to 88.4%)) did not know whether their faculty had a policy regarding drug company-student interactions.

Conclusion

In France in 2019, medical students’ exposure to pharmaceutical product promotion and incentives remains considerable and starts early during medical training. Education on promotional strategies and institutional policies should be improved to ensure responsible and ethical behaviour in prescribing medications.
Setting the top 10 priorities for obesity and weight-related research (POWeR): a stakeholder priority setting process
Authors: Butler Ailsa R , Astbury Nerys M , Goddard Lucy , Hajizadeh Anisa , Seeber Philippa , Crawley Bruce , Aveyard Paul , Jebb Susan A
Published: July 2022

Objectives

To identify and prioritise the most impactful, unanswered questions for obesity and weight-related research.

Design

Prioritisation exercise of research questions using online surveys and an independently facilitated workshop.

Setting

Online/virtual.

Participants

We involved members of the public including people living with obesity, researchers, healthcare professionals and policy-makers in all stages of this study.

Primary outcome measures

Top 10 research questions to be prioritised in future obesity and weight-related research.

Results

Survey 1 produced 941 questions, from 278 respondents. Of these, 49 questions held satisfactory evidence in the scientific literature and 149 were out of scope. The remaining 743 questions were, where necessary, amalgamated and rephrased, into a list of 149 unique and unanswered questions. In the second survey, 405 respondents ranked the questions in order of importance. During the workshop, a subset of 38 survey respondents and stakeholders, agreed a final list of 10 priority research questions through small and large group consultation and consensus. The top 10 priority research questions covered: the role of the obesogenic environment; effective weight loss and maintenance strategies; prevention in children; effective prevention and treatment policies; the role of the food industry; access to and affordability of a healthy diet; sociocultural factors associated with weight; the biology of appetite and food intake; and long-term health modelling for obesity.

Conclusions

This systematic and transparent process identified 149 unique and unanswered questions in the field of obesity and weight-related research culminating in a consensus among relevant stakeholders on 10 research priorities. Targeted research funding in these areas of top priority would lead to needed and impactful knowledge generation for the field of obesity and weight regulation and thereby improve population health.
Effective breastfeeding technique and associated factors among lactating mothers in Gidan District, North-East, Ethiopia: a community-based cross-sectional study
Authors: Asmamaw Desale Bihonegn , Habitu Yohannes Ayanaw , Negash Wubshet Debebe , Desta Dawit Zenamarkos , Mekonnen Eskedar Getie
Published: July 2022

Objective

To assess effective breastfeeding technique (EBT) and associated factors among lactating mothers in Gidan District, North-East Ethiopia.

Design

A community-based cross-sectional study.

Setting

Gidan District, North-East Ethiopia.

Participants

A total of 786 lactating mothers were included between 30 March and 29 April 2021.

Outcome

EBT.

Methods

A multistage sampling technique was employed to recruit participants. Pretested interviewer-administered questionnaires and an observational checklist were used to collect the data. Individual scores of three variables about breast feeding, namely positioning, attachment and suckling, were computed to generate the outcome variable, that is, breastfeeding technique. Binary logistic regression analyses were carried out to determine the association between independent variables and EBT. Statistical significance was declared at a value of p≤0.05 with a corresponding 95% CI.

Results

Overall, the prevalence of EBT was 42.9% (326/760). Having antenatal care follow-up (adjusted OR (AOR)=1.75; 95% CI 1.10 to 2.77), delivering at health institutions (hospital AOR=2.85; 95% CI 1.22 to 6.66 and health centre AOR=2.15; 95% CI 1.25 to 3.68), and receiving postpartum home visits by the health extension workers (HEWs) (AOR=2.12; 95% CI 1.55 to 2.92) were significantly associated with the practice of EBT.

Conclusion

The study showed that the prevalence of EBT was low. The finding highlights the importance of promoting utilisation of antenatal care follow-up, institutional delivery and postpartum home visits by HEWs, which play a substantial role in promoting EBT.
What are the barriers and facilitators to self-management of chronic conditions reported by women? A systematic review
Authors: Dwyer Lucy , Dowding Dawn , Kearney Rohna
Published: July 2022

Introduction

Pelvic organ prolapse (POP) can be effectively managed using a pessary. A scoping review found that pessary self-management appears to benefit women with no increased risk. Despite this, many are unwilling to self-manage their pessary. At present, there is a lack of understanding about what affects willingness to self-manage a pessary. However, there may be relevant, transferable findings from other literature about barriers to the self-management of other chronic conditions. Therefore, this systematic review aims to identify, appraise and synthesise the findings of published qualitative research exploring the barriers and facilitators to self-management of chronic conditions reported by women.

Methods and analysis

The systematic review will be conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a guide for the systematic review of qualitative data. A search of MEDLINE, CINAHL, Embase and PsycInfo will be undertaken to identify relevant articles that meet the eligibility criteria using the search terms ‘Women’, ‘Woman’ ‘Female,’ ‘Chronic’, ‘Long-term’, ‘Disease’, ‘Illness’, ‘Condition’ ‘Health,’ ‘Self-management,’ ‘Qualitative,’ ‘Barrier’ and ‘Facilitator’. A hand search of the reference list of non-original research identified during the search but excluded will be conducted for additional publications, which meet the inclusion and exclusion criteria. Studies published before 2005 and those not available in English will be excluded. Data relevant to the topic will be extracted and critical appraisal of all included publications undertaken.

Ethics and dissemination

No ethical or Health Research Authority approval is required to undertake the systematic review. The systematic review findings will be disseminated by publication. The findings will also inform subsequent exploratory work regarding pessary self-management.

PROSPERO registration number

CRD42022327643.
Assessing research methodologies used to evaluate inequalities in end-of-life cancer care research: a scoping review protocol
Authors: Davis Laura E , Webber Colleen , Datta Geetanjali D , Wiens Allison , Harper Sam , Hallet Julie , Coburn Natalie G , Konikoff Lauren , Tanuseputro Peter , Mahar Alyson L
Published: July 2022

Introduction

To provide equitable cancer care at the end of life, it is essential to first understand the evidence underpinning the existence of unequal cancer outcomes. Study design, measurement and analytical decisions made by researchers are a function of their social systems, academic training, values and biases, which influence both the findings and interpretation of whether inequalities or inequities exist. Methodological choices can lead to results with different implications for research and policy priorities, including where supplementary programmes and services are offered and for whom. The objective of this scoping review is to provide an overview of the methods, including study design, measures and statistical approaches, used in quantitative and qualitative observational studies of health equity in end-of-life cancer care, and to consider how these methods align with recommended approaches for studying health equity questions.

Methods and analysis

This scoping review follows Arksey and O’Malley’s expanded framework for scoping reviews. We will systematically search Medline, Embase, CINAHL and PsycINFO electronic databases for quantitative and qualitative studies that examined equity stratifiers in relation to end-of-life cancer care and/or outcomes published in English or French between 2010 and 2021. Two authors will independently review all titles, abstracts and full texts to determine which studies meet the inclusion criteria. Data from included full-text articles will be extracted into a data form that will be developed and piloted by the research team. Extracted information will be summarised quantitatively and qualitatively.

Ethics and dissemination

No ethics approval is required for this scoping review. Results will be disseminated to researchers examining questions of health equity in cancer care through scientific publication and presentation at relevant conferences.
Accidental poisoning in children: a single centre case series study in Bangladesh
Authors: Ahmed Ahsan , Hasanul Banna Siam Md , Shojon Mohammad , Mahdi Hasan Md , Raheem Enayetur , Hossain Mohammad Sorowar
Published: July 2022

Background

Accidental poisoning is a leading cause of unintentional injuries among children in low-income and middle-income countries (LMICs). The overall aspect of this unintentional poisoning is poorly understood in Bangladesh. The objectives of this study were (1) to explore the socio-demographic factors and circumstantial context of accidental poisoning and (2) the prevalence of the type of substances causing it.

Methods

A descriptive case series study was conducted from April 2019 to February 2020 at a tertiary level hospital of the capital city Dhaka in Bangladesh. Children under 10 years of age admitted to the hospital with accidental poisoning were enrolled in this study. Parents of hospitalised children were interviewed face-to-face using a structured questionnaire. Descriptive statistics were used for data analysis.

Results

A total of 223 children were recruited in this study. Children between 2 and 5 years (60%), men (61%) and children with agility (65.5%) were among the prevalent victims. The majority of cases occurred (65%) in a nuclear family setting. Most mothers (85%) of these children were non-working and most incidents took place in parents’ homes (~82%). Nearly 70% of the poisoning incidents took place in the presence of parents and over half of these occurred in the bedroom. Kerosene was the prevalent cause (33%) of accidental poisoning while insecticide/pesticide ranked second (26.5%) followed by medicines (17%) and household chemicals (12). In one-third (31.4%) of the cases, poisoning chemicals were stored in soft drink bottles while two-thirds (67.3%) of the cases were kept in containers other than original ones. Although over 80 parents somewhat knew that chemicals could be harmful to the children if ingested, most of them did not take the safety measures.

Conclusion

In this present study we found that preschool-aged children were more victims of accidental poisoning mostly by ingesting kerosene and a majority of the incidents took place in the bedroom while parents were present at home. Our study findings would serve as a baseline for designing future intervention studies and policies.
Refining nosology by modelling variation among facial phenotypes: the RASopathies
Authors: Matthews Harold , Vanneste Michiel , Katsura Kaitlin , Aponte David , Patton Michael , Hammond Peter , Baynam Gareth , Spritz Richard , Klein Ophir D , Hallgrimsson Benedikt , Peeters Hilde , Claes Peter
Published: July 2022

Background

In clinical genetics, establishing an accurate nosology requires analysis of variations in both aetiology and the resulting phenotypes. At the phenotypic level, recognising typical facial gestalts has long supported clinical and molecular diagnosis; however, the objective analysis of facial phenotypic variation remains underdeveloped. In this work, we propose exploratory strategies for assessing facial phenotypic variation within and among clinical and molecular disease entities and deploy these techniques on cross-sectional samples of four RASopathies: Costello syndrome (CS), Noonan syndrome (NS), cardiofaciocutaneous syndrome (CFC) and neurofibromatosis type 1 (NF1).

Methods

From three-dimensional dense surface scans, we model the typical phenotypes of the four RASopathies as average ‘facial signatures’ and assess individual variation in terms of direction (what parts of the face are affected and in what ways) and severity of the facial effects. We also derive a metric of phenotypic agreement between the syndromes and a metric of differences in severity along similar phenotypes.

Results

CFC shows a relatively consistent facial phenotype in terms of both direction and severity that is similar to CS and NS, consistent with the known difficulty in discriminating CFC from NS based on the face. CS shows a consistent directional phenotype that varies in severity. Although NF1 is highly variable, on average, it shows a similar phenotype to CS.

Conclusions

We established an approach that can be used in the future to quantify variations in facial phenotypes between and within clinical and molecular diagnoses to objectively define and support clinical nosologies.
Genetic spectrum of Chinese children with cystic fibrosis: comprehensive data analysis from the main referral centre in China
Authors: Shen Yuelin , Tang Xiaolei , Chen Qionghua , Xu Hui , Liu Hui , Liu Jinrong , Yang Haiming , Li Huimin , Zhao Shunying
Published: July 2022

Background and objectives

Cystic fibrosis (CF) is a heterogeneous disease with a diverse genetic spectrum among populations. Few patients with CF of Chinese origin have been reported worldwide. The objective of this study is to characterise the genotypic features of CF in Chinese children.

Methods

We recruited and characterised the genetic manifestations of 103 Chinese children with CF in Beijing Children’s Hospital from 2010 to 2022. Whole-exome sequencing were performed to define the genotypes. Meanwhile, other 99 genetically confirmed patients with Chinese origin described in 45 references were also summarised.

Results

158 different variants including 23 novel observations were identified after sequencing. The majority ofCFTRvariants (82.3%) in Chinese have been observed only once or twice. 43.7% of the variants were only identified in patients of Chinese origin. The c.2909G>A(p.Gly970Asp), c.1766+5G>T and c.1657C>T(p.Arg553X) were the most frequent variants among Chinese patients, with allele frequency of 12.1%, 5.4% and 3.6%, respectively. The first two variants both showed significant Chinese ethnic tendency, while the latter one most likely came from Europeans for historical reasons. They also demonstrated significant differences in geographical distribution. c.1521_1523delCTT(p.F508del) was rarely observed in patients of pure Chinese origin, with an allele frequency of 1.8%. Two de novo variants (c.960dupA[p.Ser321IlefsX43] and c.2491-2A>G) and two deep-intronic variants (c.3718–2477C>T and c.3874-4522A>G) were identified, which were also quite rare among Chinese.

Conclusions

The genetic spectrum of CF in Chinese is unique and quite different from that observed in Caucasians. The geographical distributions of the most frequent variants were reported for the first time.