bluuebunny/crossref_metadata_2025 huggingface dataset:
How to vocode: Using channel vocoders for cochlear-implant research
Authors: Cychosz Margaret , Winn Matthew B. , Goupell Matthew J.
Published: April 2024

The channel vocoder has become a useful tool to understand the impact of specific forms of auditory degradation—particularly the spectral and temporal degradation that reflect cochlear-implant processing. Vocoders have many parameters that allow researchers to answer questions about cochlear-implant processing in ways that overcome some logistical complications of controlling for factors in individual cochlear implant users. However, there is such a large variety in the implementation of vocoders that the term “vocoder” is not specific enough to describe the signal processing used in these experiments. Misunderstanding vocoder parameters can result in experimental confounds or unexpected stimulus distortions. This paper highlights the signal processing parameters that should be specified when describing vocoder construction. The paper also provides guidance on how to determine vocoder parameters within perception experiments, given the experimenter's goals and research questions, to avoid common signal processing mistakes. Throughout, we will assume that experimenters are interested in vocoders with the specific goal of better understanding cochlear implants.
Understanding the relationship between the Bering Sea Cold Pool and vocal presence of odontocetes in the context of climate change
Authors: Miksis-Olds Jennifer L. , Seger Kerri D. , Johnson Jennifer J.
Published: April 2024

The Cold Pool is a subsurface layer with water temperatures below 2 °C that is formed in the eastern Bering Sea. This oceanographic feature of relatively cooler bottom temperature impacts zooplankton and forage fish dynamics, driving different energetic pathways dependent upon Bering Sea climatic regime. Odontocetes echolocate to find prey, so tracking foraging vocalizations acoustically provides information to understand the implications of climate change on Cold Pool variability influencing regional food web processes. Vocal foraging dynamics of ice-associated and seasonally migrant marine mammal species suggest that sperm whales spend more time searching for prey in warm years when the Cold Pool is reduced but are more successful at capturing prey during cold years when the Cold Pool is stronger. Beluga whale foraging vocal activity was relatively consistent across climate regimes but peaked during the warm regime. Killer whale foraging vocal activity peaked in both warm and cold regimes with indicators of different ecotypes exploiting changing prey conditions across climate regimes. Foraging activity of odontocete apex predators may serve as a sentinel indicator of future ecosystem change related to prey availability that is linked to a diminishing Cold Pool as water temperatures rise and seasonal sea ice decreases due to climate change.
Women and Men Professors as Role Models and Their Effect on Academics’ Career Decisions
Authors: Lesch Lara , Scharfenkamp Katrin , Wicker Pamela
Published: April 2024

This study investigated the perception of role model attributes of women and men sport professors, how these attributes influence the choice of academic role models, and how such role models affect career objectives. The study draws on social cognitive (career) theory. Data were collected with a quantitative online survey (N = 792) targeted at major students (under- and postgraduate [n = 515], doctoral [n = 122]), and faculty members (postdoc researchers [n = 43] and professors [n = 112]), in sport management/economics/sociology or a general sports-science program in different countries. Data were analyzed by mean comparisons and regression analyses. The results suggest that women perceive women professors as more competent and as better teachers. Women perceive more similarity with women professors, and the intention to imitate the role model seems to influence both women and men in their role model choice. Women’s interest in an academic career is positively impacted by women and men role models, while men’s career objectives are only influenced by men professors. Implications of the study are that the applied theoretical framework is appropriate for investigating both women’s and men’s role models and career objectives. Furthermore, the study helps academic policymakers and sport faculty members to understand the importance of professors as role models.
SF3A2 promotes progression and cisplatin resistance in triple-negative breast cancer via alternative splicing of MKRN1
Authors: Deng Ling , Liao Li , Zhang Yin-Ling , Yang Shao-Ying , Hu Shu-Yuan , Andriani Lisa , Ling Yun-Xiao , Ma Xiao-Yan , Zhang Fang-Lin , Shao Zhi-Ming , Li Da-Qiang
Published: April 2024

Triple-negative breast cancer (TNBC) is the deadliest subtype of breast cancer owing to the lack of effective therapeutic targets. Splicing factor 3a subunit 2 (SF3A2), a poorly defined splicing factor, was notably elevated in TNBC tissues and promoted TNBC progression, as confirmed by cell proliferation, colony formation, transwell migration, and invasion assays. Mechanistic investigations revealed that E3 ubiquitin-protein ligase UBR5 promoted the ubiquitination-dependent degradation of SF3A2, which in turn regulated UBR5, thus forming a feedback loop to balance these two oncoproteins. Moreover, SF3A2 accelerated TNBC progression by, at least in part, specifically regulating the alternative splicing of makorin ring finger protein 1 (
MKRN1
) and promoting the expression of the dominant and oncogenic isoform,
MKRN1-T1
. Furthermore, SF3A2 participated in the regulation of both extrinsic and intrinsic apoptosis, leading to cisplatin resistance in TNBC cells. Collectively, these findings reveal a previously unknown role of SF3A2 in TNBC progression and cisplatin resistance, highlighting SF3A2 as a potential therapeutic target for patients with TNBC.
An in vitro neurogenetics platform for precision disease modeling in the mouse
Authors: Cortes Daniel E. , Escudero Mélanie , Korgan Austin C. , Mitra Arojit , Edwards Alyssa , Aydin Selcan C. , Munger Steven C. , Charland Kevin , Zhang Zhong-Wei , O'Connell Kristen M. S. , Reinholdt Laura G. , Pera Martin F.
Published: April 2024

The power and scope of disease modeling can be markedly enhanced through the incorporation of broad genetic diversity. The introduction of pathogenic mutations into a single inbred mouse strain sometimes fails to mimic human disease. We describe a cross-species precision disease modeling platform that exploits mouse genetic diversity to bridge cell-based modeling with whole organism analysis. We developed a universal protocol that permitted robust and reproducible neural differentiation of genetically diverse human and mouse pluripotent stem cell lines and then carried out a proof-of-concept study of the neurodevelopmental gene
DYRK1A
. Results in vitro reliably predicted the effects of genetic background on
Dyrk1a
loss-of-function phenotypes in vivo. Transcriptomic comparison of responsive and unresponsive strains identified molecular pathways conferring sensitivity or resilience to
Dyrk1a1A
loss and highlighted differential messenger RNA isoform usage as an important determinant of response. This cross-species strategy provides a powerful tool in the functional analysis of candidate disease variants identified through human genetic studies.
Recurrent mutations in tumor suppressor
FBXW7
bypass Wnt/β-catenin addiction in cancer
Authors: Zhong Zheng , Virshup David M.
Published: April 2024

Pathologic Wnt/β-catenin signaling drives various cancers, leading to multiple approaches to drug this pathway. Appropriate patient selection can maximize success of these interventions. Wnt ligand addiction is a druggable vulnerability in
RNF43
-mutant/
RSPO
-fusion cancers. However, pharmacologically targeting the biogenesis of Wnt ligands, e.g., with PORCN inhibitors, has shown mixed therapeutic responses, possibly due to tumor heterogeneity. Here, we show that the tumor suppressor
FBXW7
is frequently mutated in
RNF43
-mutant/
RSPO
-fusion tumors, and
FBXW7
mutations cause intrinsic resistance to anti-Wnt therapies. Mechanistically, FBXW7 inactivation stabilizes multiple oncoproteins including Cyclin E and MYC and antagonizes the cytostatic effect of Wnt inhibitors. Moreover, although
FBXW7
mutations do not mitigate β-catenin degradation upon Wnt inhibition,
FBXW7
-mutant
RNF43
-mutant/
RSPO
-fusion cancers instead lose dependence on β-catenin signaling, accompanied by dedifferentiation and loss of lineage specificity. These
FBXW7
-mutant Wnt/β-catenin–independent tumors are susceptible to multi–cyclin-dependent kinase inhibition. An in-depth understanding of primary resistance to anti–Wnt/β-catenin therapies allows for more appropriate patient selection and use of alternative mechanism-based therapies.
Therapeutic administration of a cross-reactive mAb targeting the fusion glycoprotein of Nipah virus protects nonhuman primates
Authors: Zeitlin Larry , Cross Robert W. , Woolsey Courtney , West Brandyn R. , Borisevich Viktoriya , Agans Krystle N. , Prasad Abhishek N. , Deer Daniel J. , Stuart Lauren , McCavitt-Malvido Maria , Kim Do H. , Pettitt James , Crowe James E. , Whaley Kevin J. , Veesler David , Dimitrov Antony , Abelson Dafna M. , Geisbert Thomas W. , Broder Christopher C.
Published: April 2024

No licensed vaccines or therapies exist for patients infected with Nipah virus (NiV), although an experimental human monoclonal antibody (mAb) cross-reactive to the NiV and Hendra virus (HeV) G glycoprotein, m102.4, has been tested in a phase 1 trial and has been provided under compassionate use for both HeV and NiV exposures. NiV is a highly pathogenic zoonotic paramyxovirus causing regular outbreaks in humans and animals in South and Southeast Asia. The mortality rate of NiV infection in humans ranges from 40% to more than 90%, making it a substantial public health concern. The NiV G glycoprotein mediates host cell attachment, and the F glycoprotein facilitates membrane fusion and infection. We hypothesized that a mAb against the prefusion conformation of the F glycoprotein may confer better protection than m102.4. To test this, two potent neutralizing mAbs against NiV F protein, hu1F5 and hu12B2, were compared in a hamster model. Hu1F5 provided superior protection to hu12B2 and was selected for comparison with m102.4 for the ability to protect African green monkeys (AGMs) from a stringent NiV challenge. AGMs were exposed intranasally to the Bangladesh strain of NiV and treated 5 days after exposure with either mAb (25 milligrams per kilogram). Whereas only one of six AGMs treated with m102.4 survived until the study end point, all six AGMs treated with hu1F5 were protected. Furthermore, a reduced 10 milligrams per kilogram dose of hu1F5 also provided complete protection against NiV challenge, supporting the upcoming clinical advancement of this mAb for postexposure prophylaxis and therapy.
The Ptk2-Pma1 pathway enhances tolerance to terbinafine in
Trichophyton rubrum
Authors: Ishii Masaki , Yamada Tsuyoshi , Ishikawa Kazuki , Ichinose Koji , Monod Michel , Ohata Shinya
Published: April 2024

The increasing prevalence of dermatophyte resistance to terbinafine, a key drug in the treatment of dermatophytosis, represents a significant obstacle to treatment.
Trichophyton rubrum
is the most commonly isolated fungus in dermatophytosis. In
T. rubrum
, we identified TERG_07844, a gene encoding a previously uncharacterized putative protein kinase, as an ortholog of budding yeast
Saccharomyces cerevisiae
polyamine transport kinase 2 (Ptk2), and found that
T. rubrum
Ptk2 (TrPtk2) is involved in terbinafine tolerance. In both
T. rubrum
and
S. cerevisiae
, Ptk2 knockout strains were more sensitive to terbinafine compared with the wild types, suggesting that promotion of terbinafine tolerance is a conserved function of fungal Ptk2. Pma1 is activated through phosphorylation by Ptk2 in
S. cerevisiae
. Overexpression of
T. rubrum
Pma1 (TrPma1) in
T. rubrum
Ptk2 knockout strain (ΔTrPtk2) suppressed terbinafine sensitivity, suggesting that the induction of terbinafine tolerance by TrPtk2 is mediated by TrPma1. Furthermore, omeprazole, an inhibitor of plasma membrane proton pump Pma1, increased the terbinafine sensitivity of clinically isolated terbinafine-resistant strains. These findings suggest that, in dermatophytes, the TrPtk2-TrPma1 pathway plays a key role in promoting intrinsic terbinafine tolerance and may serve as a potential target for combinational antifungal therapy against terbinafine-resistant dermatophytes.
Identification of a short sequence motif in the influenza A virus pathogenicity factor PB1-F2 required for inhibition of human NLRP3
Authors: Silva Filo , Boal-Carvalho Inês , Williams Nathalia , Chabert Mehdi , Niu Chengyue , Hedhili Dalila , Choltus Hélèna , Liaudet Nicolas , Gaïa Nadia , Karenovics Wolfram , Francois Patrice , Schmolke Mirco
Published: April 2024

Influenza A virus infection activates the NLRP3 inflammasome, a multiprotein signaling complex responsible for the proteolytic activation and release of the proinflammatory cytokine IL-1β from monocytes and macrophages. Some influenza A virus (IAV) strains encode a short 90-amino acid peptide (PB1-F2) on an alternative open reading frame of segment 2, with immunomodulatory activity. We recently demonstrated that contemporary IAV PB1-F2 inhibits the activation of NLRP3, potentially by NEK7-dependent activation. PB1-F2 binds to NLRP3 with its C-terminal 50 amino acids, but the exact binding motif was unknown. On the NLRP3 side, the interface is formed through the leucine-rich-repeat (LRR) domain, potentially in conjunction with the pyrin domain. Here, we took advantage of PB1-F2 sequences from IAV strains with either weak or strong NLRP3 interaction. Sequence comparison and structure prediction using Alphafold2 identified a short four amino acid sequence motif (TQGS) in PB1-F2 that defines NLRP3-LRR binding. Conversion of this motif to that of the non-binding PB1-F2 suffices to lose inhibition of NLRP3 dependent IL-1β release. The TQGS motif further alters the subcellular localization of PB1-F2 and its colocalization with NLRP3 LRR and pyrin domain. Structural predictions suggest the establishment of additional hydrogen bonds between the C-terminus of PB1-F2 and the LRR domain of NLRP3, with two hydrogen bonds connecting to threonine and glutamine of the TQGS motif. Phylogenetic data show that the identified NLRP3 interaction motif in PB1-F2 is widely conserved among recent IAV-infecting humans. Our data explain at a molecular level the specificity of NLRP3 inhibition by influenza A virus.

IMPORTANCE

Influenza A virus infection is accompanied by a strong inflammatory response and high fever. The human immune system facilitates the swift clearance of the virus with this response. An essential signal protein in the proinflammatory host response is IL-1b. It is released from inflammatory macrophages, and its production and secretion depend on the function of NLRP3. We had previously shown that influenza A virus blocks NLRP3 activation by the expression of a viral inhibitor, PB1-F2. Here, we demonstrate how this short peptide binds to NLRP3 and provide evidence that a four amino acid stretch in PB1-F2 is necessary and sufficient to mediate this binding. Our data identify a new virus-host interface required to block one signaling path of the innate host response against influenza A virus.
Extracellular vesicles in mycobacteria: new findings in biogenesis, host-pathogen interactions, and diagnostics
Authors: Salgueiro Vivian C. , Passemar Charlotte , Vázquez-Iniesta Lucía , Lerma Laura , Floto Andrés , Prados-Rosales Rafael
Published: April 2024

Since the discovery of extracellular vesicles (EVs) in mycobacterial species 15 years back, we have learned that this phenomenon is conserved in the
Mycobacterium
genus and has critical roles in bacterial physiology and host-pathogen interactions.
Mycobacterium tuberculosis
(
Mtb
), the tuberculosis (TB) causative agent, produces EVs both
in vitro
and
in vivo
including a diverse set of biomolecules with demonstrated immunomodulatory effects. Moreover,
Mtb
EVs (MEVs) have been shown to possess vaccine properties and carry biomarkers with diagnostic capacity. Although information on MEV biogenesis relative to other bacterial species is scarce, recent studies have shed light on how MEVs originate and are released to the extracellular space. In this minireview, we discuss past and new information about the vesiculogenesis phenomenon in
Mtb
, including biogenesis, MEV cargo, aspects in the context of host-pathogen interactions, and applications that could help to develop effective tools to tackle the disease.
Taqman PACMAN: a simple molecular approach for positive rapid antigen test confirmation during periods of low prevalence
Authors: McCracken Gregory R. , Patriquin Glenn , Hatchette Todd F. , Davidson Ross J. , Goodall Barbara , Barrett Lisa , MacDonald James , Heinstein Charles , Pettipas Janice , Ross John , LeBlanc Jason J.
Published: April 2024

Antigen-based rapid diagnostic tests (Ag-RDTs) were widely deployed to enhance SARS-CoV-2 testing capacity during the COVID-19 pandemic. Consistent with national guidance for low prevalence settings, positive Ag-RDTs were confirmed using nucleic acid amplification tests (NAATs) to avoid false positive results. However, increasing demands for positive Ag-RDT confirmation competed with other testing priorities in clinical laboratories. This work hypothesized that real-time RT-PCR without nucleic acid extraction (NAE) would be sufficiently sensitive to support positive Ag-RDT confirmation. Ag-RDT and NAAT results from community-based asymptomatic testing sites prior to the omicron variant wave were compared to calculate the weekly false positive rate (FPR) and false detection rate (FDR). Real-time RT-PCR was compared with and without NAE using 752 specimens previously tested positive for SARS-CoV-2 using commercial NAATs and 344 specimens from Ag-RDT-positive individuals. The impact of SARS-CoV-2 prevalence on laboratory resources required to sustain Ag-RDT confirmation was modeled for the RT-PCR with and without NAE. Overall, FPR was low [0.07% (222/330,763)] in asymptomatic testing sites, but FDR was high [30.7% (222/724)]. When RT-PCR was compared with and without NAE, 100% concordance was obtained with NAAT-positive specimens, including those from Ag-RDT-positive individuals. NAE-free RT-PCR significantly reduced time to results, human resources, and overall costs. A 30.7% FDR reaffirms the need for NAAT-based confirmation of positive Ag-RDT results during low SARS-CoV-2 prevalence. NAE-free RT-PCR was shown to be a simple and cost-sparing NAAT-based solution for positive Ag-RDT confirmation, and its implementation supported data-driven broader Ag-RDT deployment into communities, workplaces, and households.

IMPORTANCE

Rapid antigen testing for SARS-CoV-2 was widely deployed during the COVID-19 pandemic. In settings of low prevalence, national guidance recommends that positive antigen test results be confirmed with molecular testing. Given the high testing burden on clinical laboratories during the COVID-19 pandemic, the high volume of positive antigen tests submitted for confirmatory testing posed challenges for laboratory workflow. This study demonstrated that a simple PCR method without prior nucleic acid purification is an accurate and cost-effective solution for positive rapid antigen test confirmation. Implementing this method allowed molecular confirmatory testing for positive antigen tests to be sustained as antigen testing was expanded into large populations such as workplaces, schools, and households.
Osteoid osteoma of the distal radius presenting as an inconspicuous swelling in a young child
Authors: Nachu Monish , Tontanahal Sagar , Kurian Binu T
Published: April 2024

Osteoid osteoma is a benign osteoblastic tumour with a predilection for the lower extremity that rarely affects the forearm. It is commonly seen in adolescents and young adults, and is seldom diagnosed in the paediatric age group. We report a boy in his early childhood who presented with a swelling over the distal forearm, which was incidentally noted by the mother 3 months ago. Plain radiographs showed diffuse sclerosis of the dorsal cortex of the distal radius. CT scan showed a central lucent nidus in the intramedullary region and surrounding sclerosis in the radial metaphysis, confirming the diagnosis of osteoid osteoma. The patient was successfully treated by surgical en bloc resection of the nidus and was asymptomatic at 1-year follow-up. Non-specific symptoms at presentation make it a challenge to diagnose osteoid osteoma in children and it needs to be considered in the differential diagnosis when radiographs show lytic lesions in the bone.
Collaborative design of a health research training programme for nurses and midwives in Tshwane district, South Africa: a study protocol
Authors: Gundo Rodwell , Mulaudzi Mavis Fhumulani
Published: April 2024

Introduction

Nurses are essential for implementing evidence-based practices to improve patient outcomes. Unfortunately, nurses lack knowledge about research and do not always understand research terminology. This study aims to develop an in-service training programme for health research for nurses and midwives in the Tshwane district of South Africa.

Methods and analysis

This protocol outlines a codesign study guided by the five stages of design thinking proposed by the Hasso-Plattner Institute of Design at Stanford University. The participants will include nurses and midwives at two hospitals in the Tshwane district, Gauteng Province. The five stages will be implemented in three phases: Phase 1: Stage 1—empathise and Stage 2—define. Exploratory sequential mixed methods including focus group discussions with nurses and midwives (n=40), face-to-face interviews (n=6), and surveys (n=330), will be used in this phase. Phase 2: Stage 3—ideate and Stage 4—prototype. A team of research experts (n=5), nurses and midwives (n=20) will develop the training programme based on the identified learning needs. Phase 3: Stage 5—test. The programme will be delivered to clinical nurses and midwives (n=41). The training programme will be evaluated through pretraining and post-training surveys and face-to-face interviews (n=4) following training. SPSS V.29 will be used for quantitative analysis, and content analysis will be used to analyse qualitative data.

Ethics and dissemination

The protocol was approved by the Faculty of Health Sciences Research Ethics Committee of the University of Pretoria (reference number 123/2023). The protocol is also registered with the National Health Research Database in South Africa (reference number GP_202305_032). The study findings will be disseminated through conference presentations and publications in peer-reviewed journals.
Supplements for cognitive ability in patients with mild cognitive impairment or Alzheimer’s disease: a protocol for systematic review and network meta-analysis of randomised controlled trials
Authors: Zhang Xin-Yue , Li Ya-Qin , Yin Zi-Han , Bao Qiong-Nan , Xia Man-Ze , Chen Zheng-Hong , Zhong Wan-Qi , Wu Ke-Xin , Yao Jin , Liang Fan-Rong
Published: April 2024

Introduction

Considering the increasing incidence of Alzheimer’s disease (AD) and mild cognitive impairment (MCI) worldwide, there is an urgent need to identify efficacious, safe and convenient treatments. Numerous investigations have been conducted on the use of supplements in this domain, with oral supplementation emerging as a viable therapeutic approach for AD or MCI. Nevertheless, given the multitude of available supplements, it becomes imperative to identify the optimal treatment regimen.

Methods and analysis

Eight academic databases and three clinical trial registries will be searched from their inception to 1 June 2023. To identify randomised controlled trials investigating the effects of supplements on patients with AD or MCI, two independent reviewers (X-YZ and Y-QL) will extract relevant information from eligible articles, while the risk of bias in the included studies will be assessed using the Rob 2.0 tool developed by the Cochrane Collaboration. The primary outcome of interest is the overall cognitive function. Pair-wise meta-analysis will be conducted using RevMan V.5.3, while network meta-analysis will be carried out using Stata 17.0 and ADDIS 1.16.8. Heterogeneity test, data synthesis and subgroup analysis will be performed if necessary. The GRADE system will be employed to assess the quality of evidence. This study is scheduled to commence on 1 June 2023 and conclude on 1 October 2023.

Ethics and dissemination

Ethics approval is not required for systematic review and network meta-analysis. The results will be submitted to a peer-reviewed journal or at a conference.

Trial registration number

PROSPERO (CRD42023414700).
Quality measures of virtual care in ambulatory healthcare environments: a scoping review
Authors: Petrie Samuel , Laur Celia , Rios Patricia , Suarez Ally , Makanjuola Oluwatoni , Burke Emeralda , Bhattacharyya Onil , Mukerji Geetha
Published: April 2024

Objectives

Delivery of virtual care increased throughout the COVID-19 pandemic and persisted after physical distancing measures ended. However, little is known about how to measure the quality of virtual care, as current measures focus on in-person care and may not apply to a virtual context. This scoping review aims to understand the connections between virtual care modalities used with ambulatory patient populations and quality measures across the Quintuple Aim (provider experience, patient experience, per capita cost, population health and health equity).

Design

Virtual care was considered any interaction between patients and/or their circle of care occurring remotely using any form of information technology. Five databases (MEDLINE, Embase, PsycInfo, Cochrane Library, JBI) and grey literature sources (11 websites, 3 search engines) were searched from 2015 to June 2021 and again in August 2022 for publications that analysed virtual care in ambulatory settings. Indicators were extracted, double-coded into the Quintuple Aim framework; patient and provider experience indicators were further categorised based on the National Academy of Medicine quality framework (safety, effectiveness, patient-centredness, timeliness, efficiency and equity). Sustainability was added to capture the potential for continued use of virtual care.

Results

13 504 citations were double-screened resulting in 631 full-text articles, 66 of which were included. Common modalities included video or audio visits (n=43), remote monitoring (n=11) and mobile applications (n=11). The most common quality indicators were related to patient experience (n=58 articles), followed by provider experience (n=25 articles), population health outcomes (n=23 articles) and health system costs (n=19 articles).

Conclusions

The connections between virtual care modalities and quality domains identified here can inform clinicians, administrators and other decision-makers how to monitor the quality of virtual care and provide insights into gaps in current quality measures. The next steps include the development of a balanced scorecard of virtual care quality indicators for ambulatory settings to inform quality improvement.
Association between proton pump inhibitors and risk of hepatic encephalopathy in patients undergoing transjugular intrahepatic portosystemic shunt: a protocol for a systematic review and meta-analysis
Authors: Su Yun , Chen Yueqiao , Zheng Jinghui , Yao Chun
Published: April 2024

Introduction

Hepatic encephalopathy (HE) is a major complication of acute liver failure, cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS) placement. Its clinical manifestations range from mild cognitive deficits to coma. Furthermore, HE is a financial burden to a patient’s family and significantly affects the patient’s quality of life. In clinical practice, proton pump inhibitors (PPIs) are widely used for the treatment of HE. The use of PPIs is associated with an increased risk of post-TIPS HE; however, findings on the risk relationship between PPIs and post-TIPS HE are inconsistent. Therefore, a systematic evaluation of the relationship is needed to further provide valid evidence for the rational use of PPIs in patients who undergo TIPS.

Methods and analysis

PubMed, Web of Science, Cochrane Library and Embase will be searched extensively for relevant information. Information from 1 July 2023 to 31 July 2023 in these databases will be included. Primary outcomes will be the use of PPIs and incidence of HE after TIPS; secondary outcomes will be survival, dose dependence and adverse events. This meta-analysis will be reported in accordance with the 50 Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The risk of bias, heterogeneity and quality of evidence of the included studies will be evaluated prior to the data analysis. All data will be analysed using Review Manager (V.5.4.1) and Stata (V.17.0) statistical software.

Ethics and dissemination

Ethical approval will not be necessary for this review and meta-analysis. The results of the study will be published in a peer-reviewed journal.

PROSPERO registration number

CRD42022359208.
Incidence of hypopituitarism in adults undergoing radiotherapy for neck and head cancer: protocol for a systematic review and meta-analysis
Authors: Barros-Sevillano Shamir , Cabanillas-Lazo Miguel , Sedano-Chiroque Franshesca L , Escajadillo-Vergara Camila , Espinoza-Martinez David , Pinedo-Torres Isabel
Published: April 2024

Introduction

When children with head and neck cancer receive radiation therapy as part of their treatment, a considerable frequency of hypopituitarism has been recognised. However, in adults, it has been little studied and it is possible that patients may be inadvertently affected. The objective is to estimate the incidence of anterior pituitary dysfunction in adults undergoing radiotherapy for head and neck cancer.

Methods and analysis

A total of five databases will be used to perform the document search: PubMed, Scopus, Web of Science (Core Collection), Ovid-MEDLINE and Embase. Cohort studies will be included without restriction by language or date. The main outcome will be the incidence of adenohypophyseal dysfunction for each axis: prolactin, growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinising hormone and follicle-stimulating hormone. Incidence meta-analysis will be performed using the Freeman-Tukey double arcsine method. In addition, a random-effects model will be used along with a 95% CI. Subgroup analyses will be performed according to tumour location, radiation dose and endocrine assessment time. Meta-regression will be applied according to patient’s age and time elapsed until diagnosis.

Ethics and disclosure

Since this will be a systematic review of published data, no ethics committee approval is required. The results will be presented at conferences and finally published in a peer-reviewed journal.

PROSPERO registration number

CRD42021235163.
Intraoperative intensive blood pressure management strategy and the outcome of patients who had an acute ischaemic stroke undergoing endovascular treatment under general anaesthesia: study protocol for a prospective randomised controlled trial
Authors: Li Binben , Niu Ting , Dai Yuanqiang , Bu Lan , Pan Ke , Lu Lingyu , Bo Lulong
Published: April 2024

Background

Endovascular thrombectomy is the recommended treatment for acute ischaemic stroke, but the optimal blood pressure management strategy during the procedure under general anaesthesia remains controversial. In this study protocol, we propose an intraoperative intensive blood pressure range (110–140 mm Hg systolic blood pressure) based on a retrospective analysis and extensive literature review. By comparing the outcomes of patients who had an acute ischaemic stroke undergoing mechanical thrombectomy under general anaesthesia with standard blood pressure management (140–180 mm Hg systolic blood pressure) versus intensive blood pressure management, we aim to determine the impact of intraoperative intensive blood pressure management strategy on patient prognosis.

Methods and analysis

The study is a double-blinded, randomised, controlled study, with patients randomised into either the standard blood pressure management group or the intensive blood pressure management group. The primary endpoint of the study will be the sequential analysis of modified Rankin Scale scores at 90 days after mechanical thrombectomy.

Ethics and dissemination

The study has been approved by the ethics committee of Shanghai Changhai Hospital with an approval number CHEC2023-015. The results of the study will be published in peer-reviewed international journals.

Trial registration number

ChiCTR2300070764.
Success in vaccination programming through community health workers: a qualitative analysis of interviews and focus group discussions from Nepal, Senegal and Zambia
Authors: Ogutu Emily A , Ellis Anna S , Hester Kyra A , Rodriguez Katie , Sakas Zoe , Jaishwal Chandni , Yang Chenmua , Dixit Sameer , Bose Anindya Sekhar , Sarr Moussa , Kilembe William , Bednarczyk Robert , Freeman Matthew C
Published: April 2024

Objectives

Community health workers are essential to front-line health outreach throughout low-income and middle-income countries, including programming for early childhood immunisation. Understanding how community health workers are engaged for successful early childhood vaccination among countries who showed success in immunisation coverage would support evidence-based policy guidance across contexts.

Design

We employed a multiple case study design using qualitative research methods.

Setting

We conducted research in Nepal, Senegal and Zambia.

Participants

We conducted 207 interviews and 71 focus group discussions with 678 participants at the national, regional, district, health facility and community levels of the health systems of Nepal, Senegal and Zambia, from October 2019 to April 2021. We used thematic analysis to investigate contributing factors of community health worker programming that supported early childhood immunisation within each country and across contexts.

Results

Implementation of vaccination programming relied principally on the (1) organisation, (2) motivation and (3) trust of community health workers. Organisation was accomplished by expanding cadres of community health workers to carry out their roles and responsibilities related to vaccination. Motivation was supported by intrinsic and extrinsic incentives. Trust was expressed by communities due to community health worker respect and value placed on their work.

Conclusion

Improvements in immunisation coverage was facilitated by community health worker organisation, motivation and trust. With the continued projection of health worker shortages, especially in low-income countries, community health workers bridged the equity gap in access to vaccination services by enabling wider reach to underserved populations. Although improvements in vaccination programming were seen in all three countries—including government commitment to addressing human resource deficits, training and remuneration; workload, inconsistency in compensation, training duration and scope, and supervision remain major challenges to immunisation programming. Health decision-makers should consider organisation, motivation and trust of community health workers to improve the implementation of immunisation programming.
Portuguese observational cross-sectional clinical imaging study protocol to investigate central dopaminergic mechanisms of successful weight loss through bariatric surgery
Authors: Pais Marta Lapo , Crisóstomo Joana , Abrunhosa Antero , Castelo-Branco Miguel
Published: April 2024

Introduction

Bariatric surgery (BS) is the treatment of choice for refractory obesity. Although weight loss (WL) reduces the prevalence of obesity-related comorbidities, not all patients maintain it. It has been suggested that central mechanisms involving dopamine receptors may play a role in successful WL. This protocol describes an observational cross-sectional study to test if the binding of central dopamine receptors is similar in individuals who responded successfully to BS and age- and gender-matched normal-weight healthy individuals (controls). As secondary goals, the protocol will investigate if this binding correlates with key parameters such as age, hormonal status, anthropometric metrics and neurobehavioural scores. Finally, as exploratory goals, we will include a cohort of individuals with obesity before and after BS to explore whether obesity and type of BS (sleeve gastrectomy and Roux-en-Y gastric bypass) yield distinct binding values and track central dopaminergic changes resulting from BS.

Methods and analysis

To address the major research question of this observational study, positron emission tomography (PET) with [11C]raclopride will be used to map brain dopamine type 2 and 3 receptors (D2/3R) non-displaceable binding potential (BPND) of individuals who have successfully responded to BS. Mean regional D2/3R BPNDvalues will be compared with control individuals by two one-sided test approaches. The sample size (23 per group) was estimated to demonstrate the equivalence between two independent group means. In addition, these binding values will be correlated with key parameters to address secondary goals. Finally, for exploratory analysis, these values will be compared within the same individuals (before and after BS) and between individuals with obesity and controls and types of BS.

Ethics and dissemination

The project and informed consent received ethical approval from the Faculty of Medicine and the Coimbra University Hospital ethics committees. Results will be disseminated in international peer-reviewed journals and conferences.
Public health relevance of medicines developed under paediatric legislation in Europe and the USA: a systematic mapping study
Authors: Volodina Anna , Jahn Albrecht , Jahn Rosa
Published: April 2024

Background

Legislation in the European Union (EU) and the USA promoting the development of paediatric medicines has contributed to new treatments for children. This study explores how such legislation responds to paediatric health needs in different country settings and globally, and whether it should be considered for wider implementation.

Methods

We searched EU and US regulatory databases for medicines with approved indications resulting from completed paediatric development between 2007 and 2018. Of 195 medicines identified, 187 could be systematically mapped to the burden of the target disease for six study countries (Australia, Brazil, Canada, Kenya, Russia, South Africa) and globally, using disability-adjusted life years (DALYs). All medicines were also screened for inclusion on the WHO Model List of Essential Medicines (EML) and the EML for children under 13 years (EMLc).

Results

The studied medicines were disproportionately focused on non-communicable diseases, which represented 68% of medicines and 21% of global paediatric DALYs. On the other hand, we found 28% of medicines for communicable, maternal, neonatal and nutritional disorders, representing 73% of global paediatric DALYs. Neonatal disorders and malaria were mapped with two medicines, tuberculosis and neglected tropical diseases with none. The gap between medicines and paediatric DALYs was greater in countries with lower income. Still, 34% of medicines are included in the EMLc and 48% in the EML.

Conclusions

Paediatric policies in the EU and the USA are only partially responsive to paediatric health needs. To be considered for wider implementation, paediatric incentives and obligations should be more targeted towards paediatric health needs. International harmonisation of legislation and alignment with global research priorities could further strengthen its impact on child health and support ongoing efforts to improve access to medicines. Furthermore, efforts should be made to ensure global access to authorised paediatric medicines.
Endoscopic resection of large non-pedunculated colorectal polyps: current standards of treatment
Authors: Taghiakbari Mahsa , Kim Dong Hyun Danny , Djinbachian Roupen , von Renteln Daniel
Published: April 2024

Colorectal cancer is a significant public health concern, and large non-pedunculated colorectal polyps pose a substantial risk for malignancy and incomplete resection, which may lead to interval cancer. The choice of resection technique is influenced by various factors, including polyp size, morphology, location, submucosal invasion depth and endoscopist expertise. For non-cancerous superficial large non-pedunculated polyps, conventional hot or cold snare polypectomy, endoscopic mucosal resection and endoscopic submucosal dissection are common techniques for non-surgical therapeutic endoscopic resection of these polyps. This manuscript provides a comprehensive review of literature on current endoscopic resection techniques for large non-pedunculated colorectal polyps, emphasising indications, advantages, limitations and outcomes.
Optimal glycaemic control and the reduced risk of colorectal adenoma and cancer in patients with diabetes: a population-based cohort study
Authors: Mao Xianhua , Cheung Ka Shing , Tan Jing-Tong , Mak Lung-Yi , Lee Chi-Ho , Chiang Chi-Leung , Cheng Ho Ming , Hui Rex Wan-Hin , Yuen Man Fung , Leung Wai Keung , Seto Wai-Kay
Published: April 2024

Objective

Whether varying degrees of glycaemic control impact colonic neoplasm risk in patients with diabetes mellitus (DM) remains uncertain.

Design

Patients with newly diagnosed DM were retrieved from 2005 to 2013. Optimal glycaemic control at baseline was defined as mean haemoglobin A1c (HbA1c)<7%. Outcomes of interest included colorectal cancer (CRC) and colonic adenoma development. We used propensity score (PS) matching with competing risk models to estimate subdistribution HRs (SHRs). We further analysed the combined effect of baseline and postbaseline glycaemic control based on time-weighted mean HbA1c during follow-up.

Results

Of 88 468 PS-matched patients with DM (mean (SD) age: 61.5 (±11.7) years; male: 47 127 (53.3%)), 1229 (1.4%) patients developed CRC during a median follow-up of 7.2 (IQR: 5.5–9.4) years. Optimal glycaemic control was associated with lower CRC risk (SHR 0.72; 95% CI 0.65 to 0.81). The beneficial effect was limited to left-sided colon (SHR 0.71; 95% CI 0.59 to 0.85) and rectum (SHR 0.71; 95% CI 0.57 to 0.89), but not right-sided colon (SHR 0.86; 95% CI 0.67 to 1.10). Setting suboptimal glycaemic control at baseline/postbaseline as a reference, a decreased CRC risk was found in optimal control at postbaseline (SHR 0.79), baseline (SHR 0.71) and both time periods (SHR 0.61). Similar associations were demonstrated using glycaemic control as a time-varying covariate (HR 0.75). A stepwise greater risk of CRC was found (P
trend
<0.001) with increasing HbA1c (SHRs 1.34, 1.30, 1.44, 1.58 for HbA1c 7.0% to <7.5%, 7.5% to <8.0%, 8.0% to <8.5% and ≥8.5%, respectively). Optimal glycaemic control was associated with a lower risk of any, non-advanced and advanced colonic adenoma (SHRs 0.73–0.87).

Conclusion

Glycaemic control in patients with DM was independently associated with the risk of colonic adenoma and CRC development with a biological gradient.
Neuroanatomical and prognostic associations of depression in Parkinson’s disease
Authors: Badenoch James B , Paris Alvar , Jacobs Benjamin Meir , Noyce Alastair J , Marshall Charles R , Waters Sheena
Published: April 2024

Background

Depression is reported as a risk factor, prodromal feature and late consequence of Parkinson’s disease (PD). We aimed to evaluate the timing, neuroanatomy and prognostic implications of depression in PD.

Methods

We used data from 434 023 participants from UK Biobank with 14.1 years of follow-up. Multivariable regression models established associations of depression with incident PD and regional brain volumes. Cox proportional hazards models assessed prognostic associations of depression in PD with incident dementia and all-cause mortality.

Results

Of 2632 individuals with incident PD, 539 (20.5%) were diagnosed with depression at some point. Depression was associated with an increased risk of subsequent PD (risk ratio 1.53, 95% CI 1.37 to 1.72). Among incident PD cases, depression prevalence rose progressively from 10 years pre-PD diagnosis (OR 2.10, 95% CI 1.57 to 2.83) to 10 years postdiagnosis (OR 3.51, 95% CI 1.33 to 9.22). Depression severity in PD was associated with reduced grey matter volume in structures including the thalamus and amygdala. Depression prior to PD diagnosis increased risk of dementia (HR 1.47, 95% CI 1.05 to 2.07) and mortality (HR 1.30, 95% CI 1.07 to 1.58).

Conclusions

This large-scale prospective study demonstrated that depression prevalence increases from 10 years before PD diagnosis and is a marker of cortical and subcortical volume loss. Depression before PD diagnosis signals a worse prognosis in terms of dementia and mortality. This has clinical implications in stratifying people with poorer cognitive and prognostic trajectory in PD.
Validation of the international MOGAD panel proposed criteria: a single-centre US study
Authors: Filippatou Angeliki G , Said Yana , Chen Haiwen , Vasileiou Eleni S , Ahmadi Gelareh , Sotirchos Elias S
Published: April 2024

Background

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disorder of the central nervous system. We aimed to evaluate the diagnostic performance of recently proposed MOGAD diagnostic criteria in a real-world patient cohort at a tertiary referral centre.

Methods

We identified all patients who were evaluated at Johns Hopkins and were MOG-IgG seropositive by cell-based assay. We retrospectively applied the proposed MOGAD diagnostic criteria.

Results

Among the 122 patients included in this study, 109 fulfilled the diagnostic criteria. Of 64 patients with clear positive MOG-IgG titre, 63 patients also satisfied the supporting clinical or MRI features. Of 58 patients with low positive or unknown MOG-IgG titre, 46 met criteria by fulfilment of the supporting features. The medical records were independently reviewed by two investigators with expertise in demyelinating disease, and patients were assigned empirical clinical diagnoses, with agreement with the application of the MOGAD diagnostic criteria in the majority of cases (90%).

Conclusions

Our findings support the diagnostic utility of the proposed MOGAD diagnostic criteria. Patients with MOGAD met the supporting clinical or MRI features almost universally, which suggests that the criteria can be used to accurately differentiate MOGAD from mimics with low-titre MOG-IgG seropositivity.