bluuebunny/crossref_metadata_2025 huggingface dataset:
Nucleus-independent transgenerational small RNA inheritance in
Caenorhabditis elegans
Authors: Rieger Itai , Weintraub Guy , Lev Itamar , Goldstein Kesem , Bar-Zvi Dana , Anava Sarit , Gingold Hila , Shaham Shai , Rechavi Oded
Published: October 2023

In
Caenorhabditis elegans
worms, epigenetic information transmits transgenerationally. Still, it is unknown whether the effects transfer to the next generation inside or outside of the nucleus. Here, we use the tractability of gene-specific double-stranded RNA–induced silencing to demonstrate that RNA interference can be inherited independently of any nuclear factors via mothers that are genetically engineered to transmit only their ooplasm but not the oocytes’ nuclei to the next generation. We characterize the mechanisms and, using RNA sequencing, chimeric worms, and sequence polymorphism between different isolates, identify endogenous small RNAs which, similarly to exogenous siRNAs, are inherited in a nucleus-independent manner. From a historical perspective, these results might be regarded as partial vindication of discredited cytoplasmic inheritance theories from the 19th century, such as Darwin’s “pangenesis” theory.
Effect of hip abduction assistance on metabolic cost and balance during human walking
Authors: Park Juneil , Nam Kimoon , Yun Juseok , Moon JunYoung , Ryu JaeWook , Park Sungjin , Yang Seungtae , Nasirzadeh Alireza , Nam Woochul , Ramadurai Sruthi , Kim Myunghee , Lee Giuk
Published: October 2023

The use of wearable robots to provide walking assistance has rapidly grown over the past decade, with notable advances made in robot design and control methods toward reducing physical effort while performing an activity. The reduction in walking effort has mainly been achieved by assisting forward progression in the sagittal plane. Human gait, however, is a complex movement that combines motions in three planes, not only the sagittal but also the transverse and frontal planes. In the frontal plane, the hip joint plays a key role in gait, including balance. However, wearable robots targeting this motion have rarely been investigated. In this study, we developed a hip abduction assistance wearable robot by formulating the hypothesis that assistance that mimics the biological hip abduction moment or power could reduce the metabolic cost of walking and affect the dynamic balance. We found that hip abduction assistance with a biological moment second peak mimic profile reduced the metabolic cost of walking by 11.6% compared with the normal walking condition. The assistance also influenced balance-related parameters, including the margin of stability. Hip abduction assistance influenced the center-of-mass movement in the mediolateral direction. When the robot assistance was applied as the center of mass moved toward the opposite leg, the assistance replaced some of the efforts that would have otherwise been provided by the human. This indicates that hip abduction assistance can reduce physical effort during human walking while influencing balance.
The role of collaborative robotics in assistive and rehabilitation applications
Authors: Kennedy Monroe
Published: October 2023

Collaborative robotics principles and advancements may transform the field of assistive and rehabilitation robotics.
Touching reality: Bridging the user-researcher divide in upper-limb prosthetics
Authors: Brown J. D. , Battaglia E. , Engdahl S. , Levay G. , Parks A. C. , Skinner E. , O’Malley M. K.
Published: October 2023

Realistically improving upper-limb prostheses is only possible if we listen to users’ actual technological needs.
Genetic vulnerability to Crohn’s disease reveals a spatially resolved epithelial restitution program
Authors: Nakata Toru , Li Chenhao , Mayassi Toufic , Lin Helen , Ghosh Koushik , Segerstolpe Åsa , Diamond Emma L. , Herbst Paula , Biancalani Tommaso , Gaddam Shreya , Parkar Saurabh , Lu Ziqing , Jaiswal Alok , Li Bihua , Creasey Elizabeth A. , Lefkovith Ariel , Daly Mark J. , Graham Daniel B. , Xavier Ramnik J.
Published: October 2023

Effective tissue repair requires coordinated intercellular communication to sense damage, remodel the tissue, and restore function. Here, we dissected the healing response in the intestinal mucosa by mapping intercellular communication at single-cell resolution and integrating with spatial transcriptomics. We demonstrated that a risk variant for Crohn’s disease, hepatocyte growth factor activator (HGFAC) Arg
509
His (R509H), disrupted a damage-sensing pathway connecting the coagulation cascade to growth factors that drive the differentiation of wound-associated epithelial (WAE) cells and production of a localized retinoic acid (RA) gradient to promote fibroblast-mediated tissue remodeling. Specifically, we showed that HGFAC R509H was activated by thrombin protease activity but exhibited impaired proteolytic activation of the growth factor macrophage-stimulating protein (MSP). In
Hgfac
R509H mice, reduced MSP activation in response to wounding of the colon resulted in impaired WAE cell induction and delayed healing. Through integration of single-cell transcriptomics and spatial transcriptomics, we demonstrated that WAE cells generated RA in a spatially restricted region of the wound site and that mucosal fibroblasts responded to this signal by producing extracellular matrix and growth factors. We further dissected this WAE cell–fibroblast signaling circuit in vitro using a genetically tractable organoid coculture model. Collectively, these studies exploited a genetic perturbation associated with human disease to disrupt a fundamental biological process and then reconstructed a spatially resolved mechanistic model of tissue healing.
Immune responses to gut bacteria associated with time to diagnosis and clinical response to T cell–directed therapy for type 1 diabetes prevention
Authors: Xie Quin Yuhui , Oh Sean , Wong Anthony , Yau Christopher , Herold Kevan C. , Danska Jayne S.
Published: October 2023

Immune-targeted therapies have efficacy for treatment of autoinflammatory diseases. For example, treatment with the T cell–specific anti-CD3 antibody teplizumab delayed disease onset in participants at high risk for type 1 diabetes (T1D) in the TrialNet 10 (TN-10) trial. However, heterogeneity in therapeutic responses in TN-10 and other immunotherapy trials identifies gaps in understanding disease progression and treatment responses. The intestinal microbiome is a potential source of biomarkers associated with future T1D diagnosis and responses to immunotherapy. We previously reported that antibody responses to gut commensal bacteria were associated with T1D diagnosis, suggesting that certain antimicrobial immune responses may help predict disease onset. Here, we investigated anticommensal antibody (ACAb) responses against a panel of taxonomically diverse intestinal bacteria species in sera from TN-10 participants before and after teplizumab or placebo treatment. We identified IgG2 responses to three species that were associated with time to T1D diagnosis and with teplizumab treatment responses that delayed disease onset. These antibody responses link human intestinal bacteria with T1D progression, adding predictive value to known T1D risk factors. ACAb analysis provides a new approach to elucidate heterogeneity in responses to immunotherapy and identify individuals who may benefit from teplizumab, recently approved by the U.S. Food and Drug Administration for delaying T1D onset.
The tumor microenvironment state associates with response to HPV therapeutic vaccination in patients with respiratory papillomatosis
Authors: Norberg Scott M. , Bai Ke , Sievers Cem , Robbins Yvette , Friedman Jay , Yang Xinping , Kenyon Meg , Ward Elizabeth , Schlom Jeffrey , Gulley James , Lankford Amy , Semnani Roshanak , Sabzevari Helen , Brough Douglas E. , Allen Clint T.
Published: October 2023

Recurrent respiratory papillomatosis (RRP) is a rare, debilitating neoplastic disorder caused by chronic infection with human papillomavirus (HPV) type 6 or 11 and characterized by growth of papillomas in the upper aerodigestive tract. There is no approved medical therapy, and patients require repeated debulking procedures to maintain voice and airway function. PRGN-2012 is a gorilla adenovirus immune-therapeutic capable of enhancing HPV 6/11–specific T cell immunity. This first-in-human, phase 1 study (NCT04724980) of adjuvant PRGN-2012 treatment in adult patients with severe, aggressive RRP demonstrates the overall safety and clinically meaningful benefit observed with PRGN-2012, with a 50% complete response rate in patients treated at the highest dose. Responders demonstrate greater expansion of peripheral HPV-specific T cells compared with nonresponders. Additional correlative studies identify an association between reduced baseline papilloma HPV gene expression, greater interferon responses and expression of
CXCL9
and
CXCL10
, and greater papilloma T cell infiltration in responders. Conversely, nonresponders were characterized by greater HPV and
CXCL8
gene expression, increased neutrophilic cell infiltration, and reduced T cell papilloma infiltration. These results suggest that papilloma HPV gene expression may regulate interferon signaling and chemokine expression profiles within the tumor microenvironment that cooperate to govern clinical response to therapeutic HPV vaccination in patients with respiratory papillomatosis.
Thermal adaptation of soil microbial growth traits in response to chronic warming
Authors: Eng Ashley Y. , Narayanan Achala , Alster Charlotte J. , DeAngelis Kristen M.
Published: October 2023

Adaptation of soil microbes due to warming from climate change has been observed, but it remains unknown what microbial growth traits are adaptive to warming. We studied bacterial isolates from the Harvard Forest Long-Term Ecological Research site, where field soils have been experimentally heated to 5°C above ambient temperature with unheated controls for 30 years. We hypothesized that Alphaproteobacteria from warmed plots have (i) less temperature-sensitive growth rates; (ii) higher optimum growth temperatures; and (iii) higher maximum growth temperatures compared to isolates from control plots. We made high-throughput measurements of bacterial growth in liquid cultures over time and across temperatures from 22°C to 37°C in 2–3°C increments. We estimated growth rates by fitting Gompertz models to the growth data. Temperature sensitivity of growth rate, optimum growth temperature, and maximum growth temperature were estimated by the Ratkowsky 1983 model and a modified Macromolecular Rate Theory (MMRT) model. To determine evidence of adaptation, we ran phylogenetic generalized least squares tests on isolates from warmed and control soils. Our results showed evidence of adaptation of higher optimum growth temperature of bacterial isolates from heated soils. However, we observed no evidence of adaptation of temperature sensitivity of growth and maximum growth temperature. Our project begins to capture the shape of the temperature response curves, but illustrates that the relationship between growth and temperature is complex and cannot be limited to a single point in the biokinetic range.

IMPORTANCE

Soils are the largest terrestrial carbon sink and the foundation of our food, fiber, and fuel systems. Healthy soils are carbon sinks, storing more carbon than they release. This reduces the amount of carbon dioxide released into the atmosphere and buffers against climate change. Soil microbes drive biogeochemical cycling and contribute to soil health through organic matter breakdown, plant growth promotion, and nutrient distribution. In this study, we determined how soil microbial growth traits respond to long-term soil warming. We found that bacterial isolates from warmed plots showed evidence of adaptation of optimum growth temperature. This suggests that increased microbial biomass and growth in a warming world could result in greater carbon storage. As temperatures increase, greater microbial activity may help reduce the soil carbon feedback loop. Our results provide insight on how atmospheric carbon cycling and soil health may respond in a warming world.
Multicenter evaluation of the BIOFIRE Joint Infection Panel for the detection of bacteria, yeast, and AMR genes in synovial fluid samples
Authors: Esteban Jaime , Salar-Vidal Llanos , Schmitt Bryan H. , Waggoner Amy , Laurent Frédéric , Abad Lelia , Bauer Thomas W. , Mazariegos Irving , Balada-Llasat Joan-Miquel , Horn Jared , Wolk Donna M. , Jefferis Alexa , Hermans Mirjam , Verhoofstad Irma , Butler-Wu Susan M. , Umali-Wilcox Minette , Murphy Caitlin , Cabrera Barbara , Craft David , von Bredow Benjamin , Leber Amy , Everhart Kathy , Dien Bard Jennifer , Flores Irvin Ibarra , Daly Judy , Barr Rebecca , Holmberg Kristen , Graue Corrin , Kensinger Bart
Published: October 2023

The bioMérieux BIOFIRE Joint Infection (JI) Panel is a multiplex
in vitro
diagnostic test for the simultaneous and rapid (~1 h) detection of 39 potential pathogens and antimicrobial resistance (AMR) genes directly from synovial fluid (SF) samples. Thirty-one species or groups of microorganisms are included in the kit, as well as several AMR genes. This study, performed to evaluate the BIOFIRE JI Panel for regulatory clearance, provides data from a multicenter evaluation of 1,544 prospectively collected residual SF samples with performance compared to standard-of-care (SOC) culture for organisms or polymerase chain reaction (PCR) and sequencing for AMR genes. The BIOFIRE JI Panel demonstrated a sensitivity of 90.9% or greater for all but six organisms and a positive percent agreement (PPA) of 100% for all AMR genes. The BIOFIRE JI Panel demonstrated a specificity of 98.5% or greater for detection of all organisms and a negative percent agreement (NPA) of 95.7% or greater for all AMR genes. The BIOFIRE JI Panel provides an improvement over SOC culture, with a substantially shorter time to result for both organisms and AMR genes with excellent sensitivity/PPA and specificity/NPA, and is anticipated to provide timely and actionable diagnostic information for joint infections in a variety of clinical scenarios.
The first established microsatellite markers to distinguish
Candida orthopsilosis
isolates and detection of a nosocomial outbreak in China
Authors: Luo Zhengyu , Ning Yating , Yu Shuying , Xiao Meng , Dai Rongchen , Chen Xinfei , Wang Yao , Kang Wei , Jiang Yan , Yu Hua , Liang Hongjie , Xu Yingchun , Sun Tianshu , Zhang Li
Published: October 2023

The infection proportion of
Candida orthopsilosis
, a member of the
C. parapsilosis
complex, has increased globally in recent years, and nosocomial outbreaks have been reported in several countries. This study aimed to establish microsatellite loci-based typing method that was able to effectively distinguish among
C. orthopsilosis
isolates. Three reference
C. orthopsilosis
genome sequences were analyzed to identify repeat loci. DNA sequences containing over eight bi- or more nucleotide repeats were selected. A total of 51 loci were initially identified, and locus-specific primers were designed and tested with 20 epidemiologically unrelated isolates. Four loci with excellent reproducibility, specificity, and resolution for molecular typing purposes were identified, and the combined discriminatory power (DP, based on 20 epidemiologically unrelated isolates) of these four loci was 1.0. Reproducibility was demonstrated by consistently testing three strains each in triplicate, and stability, demonstrated by testing 10 successive passages. Then, we collected 48
C
.
orthopsilosis
non-duplicate clinical isolates from the China Hospital Invasive Fungal Surveillance Net study to compare the DP of the microsatellite-based typing with internal transcribed spacer (ITS) and amplified fragment length polymorphism (AFLP) typing analyses, using ATCC 96139 as a reference strain. These 49 isolates were subdivided into 12 microsatellite types (COMT1–12), six AFLP types, and three ITS types, while all the isolates with the same COMT belonged to consistent AFLP and ITS type, demonstrating the high DP of our microsatellite-type method. According to our results, COMT12 was found to be the predominant type in China, and COMT5 was the second largest and responsible for causing a nosocomial outbreak. This microsatellite-type method is a valuable tool for the differentiation of
C. orthopsilosis
and could be vital for epidemiological studies to determine strain relatedness and monitor transmission.
Developing scientific literacy with a cyclic independent study assisted CURE detecting SARS-CoV-2 in wastewater
Authors: Dye Kristine
Published: October 2023

The COVID-19 pandemic has exposed a high level of scientific illiteracy and mistrust that pervades the scientific and medical communities. This finding has proven the necessity of updating current methods used to expose undergraduates to research. The research in traditional course-based undergraduate research experiences (CUREs) is limited by undergraduate time constraints, skill level, and course structure, and consequently it does not attain the learning objectives or the high-impact, relevant studies achieved in graduate-level laboratories using a cyclic trainee/trainer model. Although undergraduate independent study (ISY) research more closely matches the structure and learning objectives of graduate-level research, they are uncommon as professors and universities typically view them as a significant time and resource burden with limited return. Cyclic independent study-assisted CUREs (CIS-CUREs) combine many positive aspects of ISY graduate-level research, and CUREs by pre-training ISY research lead to facilitate CURE proposal and project semesters in a cyclic model. The CIS-CURE approach allowed undergraduate students at Stetson University to perform and disseminate more rigorous, involved, long-term, and challenging research projects, such as the surveillance of SARS-CoV-2 in wastewater. In doing so, all students would have the opportunity to participate in a high-impact research project and consequently gain a more comprehensive training, reach higher levels of research dissemination, and increase their competitiveness after graduating. Together, CIS-CUREs generate graduates with higher scientific literacy and thus combat scientific mistrust in communities.
The protein phosphatase PPKL is a key regulator of daughter parasite development in
Toxoplasma gondii
Authors: Yang Chunlin , Doud Emma H. , Sampson Emily , Arrizabalaga Gustavo
Published: October 2023

Apicomplexan parasites, including
Toxoplasma gondii
, encode many plant-like proteins, which play significant roles and present attractive targets for drug development. In this study, we have characterized the plant-like protein phosphatase PPKL, which is unique to the parasite and absent in its mammalian host. We have shown that its localization changes as the parasite divides. In non-dividing parasites, it is present in the cytoplasm, nucleus, and preconoidal region. As the parasite begins division, PPKL is enriched in the preconoidal region and the cortical cytoskeleton of nascent parasites. Later in the division, PPKL is present in the basal complex ring. Conditional knockdown of PPKL showed that it is essential for parasite propagation. Moreover, parasites lacking PPKL exhibit uncoupling of division, with normal DNA duplication but severe defects in forming daughter parasites. While PPKL depletion does not impair the duplication of centrosomes, it affects the stability of cortical microtubules. Both co-immunoprecipitation and proximity labeling identified the kinase DYRK1 as a potential functional partner of PPKL. Complete knockout of
DYRK1
causes parasites to exhibit division defects with predominantly asynchronous divisions. Global phosphoproteomics analysis revealed a significant increase in phosphorylation of the microtubule-associated protein SPM1 in PPKL-depleted parasites, suggesting that PPKL regulates cortical microtubules by mediating the phosphorylation state of SPM1. More importantly, the phosphorylation of cell cycle-associated kinase Crk1, a known regulator of daughter cell assembly, is altered in PPKL-depleted parasites. Thus, we propose that PPKL regulates daughter parasite development by influencing the Crk1-dependent signaling pathway.

IMPORTANCE

Toxoplasma gondii
can cause severe disease in immunocompromised or immunosuppressed patients and during congenital infections. Treating toxoplasmosis presents enormous challenges since the parasite shares many biological processes with its mammalian hosts, which results in significant side effects with current therapies. Consequently, proteins that are essential and unique to the parasite represent favorable targets for drug development. Interestingly,
Toxoplasma
, like other members of the phylum Apicomplexa, has numerous plant-like proteins, many of which play crucial roles and do not have equivalents in the mammalian host. In this study, we found that the plant-like protein phosphatase PPKL appears to be a key regulator of daughter parasite development. With the depletion of PPKL, the parasite shows severe defects in forming daughter parasites. This study provides novel insights into the understanding of parasite division and offers a new potential target for the development of antiparasitic drugs.
Supplemental Material: Petrogenesis of the early Permian Hongliujing granite complex in the Chinese Eastern Tianshan orogen: Evidence for crustal growth in the Central Tianshan microcontinent
Authors: He Zhen-Yu , et al.
Published: October 2023

Tables S1–S7.
Local thrombolytics via balloon-assisted intra-arterial infusion as rescue therapy for thromboembolism during endovascular coil embolisation
Authors: Fuga Michiyasu , Tanaka Toshihide , Teshigawara Akihiko , Murayama Yuichi
Published: October 2023

Thromboembolism is the most frequent complication of coil embolisation for intracranial aneurysm. Complications of thromboembolism can lead to stroke and have a serious impact on sequelae and mortality, necessitating appropriate rescue therapy. Here, we succeeded in recanalisation of an occluded stent by balloon-assisted local infusion of a thrombolytic agent following stent-assisted coil embolisation of an unruptured posterior communicating artery aneurysm. This method involves inflating a microballoon just distal to the occluded vessel and then administering a thrombolytic agent through a microcatheter. This technique may increase the rate of vessel reopening by maximising the local drug concentration. This method can be applied to any type of thrombolytic agent and helps reduce the dose of systemic drugs, which might decrease the incidence of haemorrhagic complications. Balloon-assisted intra-arterial thrombolytic infusion for an occluded vessel during endovascular coil embolisation could offer an alternative rescue therapy when conventional thrombolytic agent administration fails to improve thromboembolism.
Count Me In: an inclusive approach towards patient recruitment for clinical research studies in the NHS
Authors: Hinze Verena , Henshall Catherine , Smith Tanya , Littlejohns Jemima , Collett Zoe , Jones Helen , Maughan Daniel , Ede Roger , Moll Deborah , Marlowe Karl , Broughton Nick , Geddes John , Cipriani Andrea
Published: October 2023

Background

Participation in clinical research is associated with better patient outcomes and higher staff retention and satisfaction rates. Nevertheless, patient recruitment to mental health studies is challenging due to a reliance on clinician or patient referrals (standard approach). To empower patients and make healthcare research more equitable, we explored a novel researcher-led approach, called ‘Count Me In’ (CMI).

Objective

To evaluate a 12-month implementation of CMI in a routine clinical setting.

Methods

CMI was launched in August 2021 in a mental health National Health Service (NHS) Trust in England. Patients (aged 18+) learnt about CMI at their initial clinical appointment. Unless they opted out, they became contactable for research (via research informatics searches).

Findings

After 12 months, 368 patients opted out and 22 741 became contactable through CMI, including 2716 through the standard approach and 20 025 through electronic searches (637% increase). Of those identified via electronic searches, 738 were contacted about specific studies and 270 consented to participate. Five themes were identified based on patient and staff experiences of CMI: ‘level of awareness and accessibility of CMI’, ‘perceptions of research and perceived engagement with CMI’, ‘inclusive research practice’, ‘engagement and incentives for research participation’, and ‘relationships between clinical and research settings’.

Conclusions

CMI (vs standard) led to a larger and diverse patient cohort and was favoured by patients and staff. Yet a shift in the NHS research culture is needed to ensure that this diversity translates to actual research participation.

Clinical implications

Through collaboration with other NHS Trusts and services, key funders (National Institute for Health and Care Research) and new national initiatives (Office for Life Sciences Mental Health Mission), CMI has the potential to address recruitment challenges through rapid patient recruitment into time-sensitive country-wide studies.
Plant-based diets and the incidence of cardiovascular disease: the Million Veteran Program
Authors: Li Yanping , Wang Dong D , Nguyen Xuan-Mai T , Song Rebecca J , Ho Yuk-Lam , Hu Frank B , Willett Walter C , Wilson Peter W F , Cho Kelly , Gaziano John Michael , Djousse Luc
Published: October 2023

Background

A healthful plant-based diet was associated with lower risks of coronary heart disease and type 2 diabetes, and a favourable profile of adiposity-associated biomarkers, while an unhealthful plant-based diet was associated with elevated risk of cardiometabolic disease in health professional populations. However, little is known about the associations between plant-based dietary patterns and risk of cardiovascular disease (CVD) in US veterans.

Methods

The study population consisted of 148 506 participants who were free of diabetes, CVD and cancer at baseline in the Veterans Affairs (VA) Million Veteran Program. Diet was assessed using a Food Frequency Questionnaire at baseline. We calculated an overall Plant-Based Diet Index (PDI), a healthful PDI (hPDI) and an unhealthful PDI (uPDI). The CVD endpoints included non-fatal myocardial infarction (MI) and acute ischaemic stroke (AIS) identified through high-throughput phenotyping algorithms approach and fatal CVD events identified by searching the National Death Index.

Results

With up to 8 years of follow-up, we documented 5025 CVD cases. After adjustment for confounding factors, a higher PDI was significantly associated with a lower risk of CVD (HR comparing extreme quintiles=0.75, 95% CI 0.68 to 0.82, Ptrend<0.0001). We observed an inverse association between hPDI and the risk of CVD (HR comparing extreme quintiles=0.71, 95% CI 0.64 to 0.78, Ptrend<0.001), whereas uPDI was positively associated with the risk of CVD (HR comparing extreme quintiles=1.12, 95% CI 1.02 to 1.24, Ptrend<0.001). We found similar associations of hPDI with subtypes of CVD; a 10-unit increment in hPDI was associated with HRs (95% CI) of 0.81 (0.75 to 0.87) for fatal CVD, 0.86 (0.79 to 0.94) for non-fatal MI and 0.86 (0.78 to 0.95) for non-fatal AIS.

Conclusions

Plant-based dietary pattern enriched with healthier plant foods was associated with a substantially lower CVD risk in US veterans.
Efficacy and safety of therapeutic HPV vaccines to treat CIN 2/CIN 3 lesions: a systematic review and meta-analysis of phase II/III clinical trials
Authors: Ibrahim Khalil Ahmadaye , Zhang Li , Muwonge Richard , Sauvaget Catherine , Basu Partha
Published: October 2023

Objectives

We aim to assess the efficacy and safety of therapeutic human papillomavirus (HPV) vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 (CIN 2/3).

Design

Systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.

Data sources

PubMed, Embase, Web of Science, Global Index Medicus and CENTRAL Cochrane were searched up to 31 January 2022.

Eligibility criteria

Phase II/III randomised controlled trials (RCTs) and single-arm studies reporting the efficacy of therapeutic vaccines to achieve regression of CIN 2/3 lesions were included. Studies evaluating only safety and side effects of the vaccine were excluded.

Data extraction and synthesis

Two independent reviewers extracted data and evaluated study quality. A random-effect model was used to pool the proportions of regression and/or HPV clearance.

Results

12 trials met the inclusion criteria. Out of 734 women (all studies considered) receiving therapeutic HPV vaccine for CIN 2/3, 414 regressed to normal/CIN 1 with an overall proportion of regression of 0.54 (95% CI 0.39 to 0.69) for vaccinated group; 166 women (from five RCTs) receiving placebo only achieving a pooled normal/CIN 1 regression of 0.27 (95% CI 0.20 to 0.34). When including only the five two-arm studies, the regression proportion for the 410 vaccine group participants was higher than that of the 166 control group participants (relative risk (RR) 1.52; 95% CI 1.14 to 2.04). The pooled proportion of high-risk human papillomavirus (hrHPV) clearance was 0.42 (95% CI 0.32 to 0.52) in the vaccine group (six studies with a total of 357 participants) and 0.17 (95% CI 0.11 to 0.26) in the control group (three RCTs with a total of 104 participants). Based on these three RCTs, the hrHPV clearance was significantly higher in the vaccinated group (250 participants) compared with the control group (RR 2.03; 95% CI 1.30 to 3.16). Similar results were found regarding HPV 16/18 clearance. No significant unsolicited adverse events have been consistently reported.

Conclusions

The efficacy of the therapeutic vaccines in the treatment of CIN 2/3 was modest. Implementation issues such as feasibility, acceptability, adoption and cost-effectiveness need to be further studied.

PROSPERO registration number

CRD42022307418.
Evaluation of the safety status of intrahospital transfer of critically ill patients from the perspective of emergency and ICU nurses: a cross-sectional study in Iran
Authors: Hashemian Maryam , Salami Zahra , Azizpour Islam , Mirzaei Alireza
Published: October 2023

Objective

Critically ill patients often require intrahospital transfer (IHT) for diagnostic and therapeutic procedures. However, this process carries potential risks and can harm the patient’s safety. This study aimed to assess the safety of IHT for critically ill patients by gathering feedback from emergency and intensive care unit (ICU) nurses.

Design

A cross-sectional study.

Setting

A study was conducted in Ardabil City, Iran’s educational and medical hospitals. The study involved 288 emergency and ICU nurses. The data were collected through a paper-based form, which included demographic and work-related characteristics and an IHT safety scale.

Results

The mean score of IHT was 75.2±15.53. The results of multiple regression analysis showed that work experience (B=0.291, p=0.011), perception of IHT safety (B=0.196, p=0.003), education level (B=−0.123, p=0.038) and equipment checker (B=−0.121, p=0.045), variables were the predictors of IHT safety.

Conclusion

The study found that the safety level during the interhospital transfer (IHT) was low. Hospitals aim to create a safe environment that minimises the risks associated with IHT. Therefore, they must identify potential risks during the transfer process and take necessary measures to mitigate them. Practical strategies that can be employed include using experienced nursing staff, conducting equipment checks, ensuring a complete understanding of the tools and technologies involved in the transfer process, and increasing awareness of IHT safety.
A qualitative study exploring experiences of the safetxt digital health intervention to reduce sexually transmitted infections in young people in the UK
Authors: Berendes Sima , Gubijev Anasztazia , French Rebecca , Hickson Ford Colin Ian , Free Caroline
Published: October 2023

Objectives

People aged 16–24 are more likely than other age groups to acquire sexually transmitted infections (STI). Safetxt was a randomised controlled trial of a theory-based digital health intervention to reduce STIs among 16–24 year-old people in the UK. We report results of qualitative research regarding participants’ perceptions and experiences of the intervention and trial participation.

Design

Qualitative thematic analysis following a critical realist paradigm of written open feedback comments provided in the 12-month follow-up questionnaire and semistructured interviews.

Setting

Safetxt trial participants were recruited from UK sexual health clinics.

Participants

Trial inclusion criteria: people aged 16–24 diagnosed with or treated for chlamydia, gonorrhoea or non-specific urethritis. Optional open feedback provided by 3526 of 6248 safetxt participants at 12 months and interviews with a purposive sample of 18 participants after the trial.

Results

We summarise and report results in seven broad themes. According to recipients, the safetxt intervention increased awareness of the importance of avoiding STIs and ways to prevent them. Participants reported improved confidence, agency, sexual well-being and communication about sexual health with partners, friends and family. Recipients attributed increased condom use, increased STI testing after (rather than before) sex with new partners, and more confident partner notification to the intervention. Recipients described a reduced sense of isolation and stigma in having an STI. Control group participants reported that having had an STI and receiving control texts asking them to report any changes in contact details acted as reminders to use condoms and get tested. We also summarise participant recommendations for future interventions and studies.

Conclusions

While control group participants reported precautionary behaviours were ‘triggered’ by trial participation, intervention recipients reported additional benefits of the intervention in increasing precautionary behaviours and in broader aspects of sexual health such as confidence, communication, emotional well-being and agency.

Trial registration

ISRCTN registryISRCTN64390461.
Exploring older care recipients’ sleep status as a predictor for informal carer distress: evidence from New Zealand’s interRAI home care assessment data
Authors: Gibson Rosemary , Abey-Nesbit Rebecca , Gander Philippa , Parsons Matthew
Published: October 2023

Objectives

Understanding factors affecting informal carers’ well-being is important to support healthy ageing at home. Sleep disturbances of care recipients are increasingly recognised as affecting the well-being of both parties. This research assesses the relationship between indicators of care recipients’ sleep status and carer distress, as well as carer distress with subsequent admission to residential aged care, using prospectively collected Home Care International Residential Assessment Instrument (interRAI-HC) assessment data.

Participants

Data were sourced from 127 832 assessments conducted between 2012 and 2019 for people aged 55 years or older who had support from at least one informal carer. The majority (59.4%) of care recipients were female and 59.1% were defined as having cognitive impairment or dementia (CIoD).

Setting

New Zealand.

Design

Logistic regression modelling was used to assess the independent relationships between indicators of care recipients’ sleep status (difficulty sleeping and fatigue) and primary caregivers’ distress (feeling overwhelmed or distressed). Kaplan meier curves illustrated the subsequent relationship between caregiver distress and care recipients’ transitions to aged residential care.

Results

Care recipients’ sleeping difficulty (32.4%) and moderate–severe fatigue (46.6%) were independently associated with caregiver distress after controlling for key demographic and health factors included in the assessment. Distress was reported by 39.9% of informal caregivers and was three times more likely among those supporting someone with a CIoD. Caregiver distress was significantly associated with care recipients’ earlier admission into aged residential care.

Conclusions

Indicators of sleep disturbance among care recipients are associated with increased likelihood of carer distress. This has implications for managing the overall home-care situation and long-term care needs, as well as the well-being of both parties. Findings will inform research and development of measures, services and interventions to improve the sleep and waking health of older people, including those with CIoD and family caregivers.
Clinical decision support tools for paediatric sepsis in resource-poor settings: an international qualitative study
Authors: Jimenez-Zambrano Andrea , Ritger Carly , Rebull Margaret , Wiens Matthew O , Kabajaasi Olive , Jaramillo-Bustamante Juan Camilo , Argent Andrew C , Kissoon Niranjan , Schlapbach Luregn J , Sorce Lauren R , Watson R Scott , Dorsey Holliman Brooke , Sanchez-Pinto Lazaro N , Bennett Tellen D
Published: October 2023

Objective

New paediatric sepsis criteria are being developed by an international task force. However, it remains unknown what type of clinical decision support (CDS) tools will be most useful for dissemination of those criteria in resource-poor settings. We sought to design effective CDS tools by identifying the paediatric sepsis-related decisional needs of multidisciplinary clinicians and health system administrators in resource-poor settings.

Design

Semistructured qualitative focus groups and interviews with 35 clinicians (8 nurses, 27 physicians) and 5 administrators at health systems that regularly provide care for children with sepsis, April–May 2022.

Setting

Health systems in Africa, Asia and Latin America, where sepsis has a large impact on child health and healthcare resources may be limited.

Participants

Participants had a mean age of 45 years, a mean of 15 years of experience, and were 45% female.

Results

Emergent themes were related to the decisional needs of clinicians caring for children with sepsis and to the needs of health system administrators as they make decisions about which CDS tools to implement. Themes included variation across regions and institutions in infectious aetiologies of sepsis and available clinical resources, the need for CDS tools to be flexible and customisable in order for implementation to be successful, and proposed features and format of an ideal paediatric sepsis CDS tool.

Conclusion

Findings from this study will directly contribute to the design and implementation of CDS tools to increase the uptake and impact of the new paediatric sepsis criteria in resource-poor settings.
Association between plant-based or animal-based dietary pattern and plasma glucose during oral glucose tolerance test among Chinese women with gestational diabetes mellitus: a prospective cohort study
Authors: Chen Xiao Qian , Zheng Qingxiang , Liao Yan Ping , Jiang Xiu Min , Gao Xiao Xia , Pan Yu-Qing , Li JiaNing , Liu RuLin
Published: October 2023

Objective

This study explored whether plant-based and animal-based dietary patterns are associated with plasma glucose levels during oral glucose tolerance test in women with gestational diabetes mellitus (GDM).

Design

A prospective cohort study was conducted using a Food Frequency Questionnaire to collect dietary data. Dietary patterns were derived using principal component analysis. Multivariate logistic regression analysis was performed to explore the association between dietary patterns and plasma glucose levels. Stratified analyses were conducted according to maternal age, prepregnancy body mass index (BMI) and other confounders.

Setting and participants

The study, conducted in January 2022 in two hospitals in Fujian, China, involved 424 women diagnosed with GDM using a 75 g 2-hour oral glucose tolerance test at 24–28 gestational weeks.

Results

Six maternal dietary patterns (plant based and animal based) were identified. Participants with plant-based pattern had lower 2-hour plasma glucose levels than those with animal-based pattern (β=−0.314; 95% CI (−0.596 to –0.032)). After adjusting the regression model covariates, this significant association remained (β=−0.288; 95% CI (−0.568 to –0.008)) and appeared more pronounced in women aged 30 years or above and those with prepregnancy BMI<24 kg/m2.

Conclusions

Plant-based pattern is associated with lower plasma glucose levels in women with GDM, which is valuable information for dietary counselling and intervention.
What is the future of artificial intelligence in obstetrics? A qualitative study among healthcare professionals
Authors: Fischer Anne , Rietveld Anna , Teunissen Pim , Hoogendoorn Mark , Bakker Petra
Published: October 2023

Objective

This work explores the perceptions of obstetrical clinicians about artificial intelligence (AI) in order to bridge the gap in uptake of AI between research and medical practice. Identifying potential areas where AI can contribute to clinical practice, enables AI research to align with the needs of clinicians and ultimately patients.

Design

Qualitative interview study.

Setting

A national study conducted in the Netherlands between November 2022 and February 2023.

Participants

Dutch clinicians working in obstetrics with varying relevant work experience, gender and age.

Analysis

Thematic analysis of qualitative interview transcripts.

Results

Thirteen gynaecologists were interviewed about hypothetical scenarios of an implemented AI model. Thematic analysis identified two major themes: perceived usefulness and trust. Usefulness involved AI extending human brain capacity in complex pattern recognition and information processing, reducing contextual influence and saving time. Trust required validation, explainability and successful personal experience. This result shows two paradoxes: first, AI is expected to provide added value by surpassing human capabilities, yet also a need to understand the parameters and their influence on predictions for trust and adoption was expressed. Second, participants recognised the value of incorporating numerous parameters into a model, but they also believed that certain contextual factors should only be considered by humans, as it would be undesirable for AI models to use that information.

Conclusions

Obstetricians’ opinions on the potential value of AI highlight the need for clinician-AI researcher collaboration. Trust can be built through conventional means like randomised controlled trials and guidelines. Holistic impact metrics, such as changes in workflow, not just clinical outcomes, should guide AI model development. Further research is needed for evaluating evolving AI systems beyond traditional validation methods.
Qualitative study exploring the perspectives of emerging adults with type 1 diabetes after transfer to adult care from a paediatric diabetes centre in Montreal, Canada
Authors: Vaillancourt Monica , Mok Elise , Frei Jennifer , Dasgupta Kaberi , Rahme Elham , Bell Lorraine , Da Costa Deborah , Nakhla Meranda
Published: October 2023

Introduction

Among youth living with type 1 diabetes (T1D), the increasing demands to diabetes self-care and medical follow-up during the transition from paediatric to adult care has been associated with greater morbidity and mortality. Inadequate healthcare support for youth during the transition care period could exacerbate psychosocial risks and difficulties that are common during emerging adulthood. The current investigation sought to explore the post-transfer perceptions of emerging adults living with T1D relating to their transition to adult care.

Research design and methods

Thirty-three emerging adults living with T1D were recruited during paediatric care and contacted for a semistructured interview post-transfer to adult care (16.2±4.2 months post-transfer) in Montreal, Canada. We analysed data using thematic analysis.

Results

We identified four key themes: (1) varied perceptions of the transition process from being quick and abrupt with minimal advice or information from paediatric healthcare providers (HCP) to more positive including a greater motivation for self-management and the transition being concurrent with the developmental period; (2) facilitators to the transition process included informational and tangible social support from HCPs and family or friends, a positive relationship with adult HCP and a greater ease in communicating with the adult care clinic or adult HCP; (3) barriers to adequate transition included lack of advice or information from paediatric HCPs, loss of support from HCPs and friends or family, the separation of healthcare services and greater difficulty in making appointments with adult clinic or HCP and (4) participants recommendations for improving the transition included increasing the length and frequency of appointments in adult care, having access to educational information, and better transition preparation from paediatric HCPs.

Conclusions

The experiences and perceptions of emerging adults are invaluable to guide the ongoing development and improvement of transition programmes for childhood-onset chronic illnesses.
Scale-up of the Australian Fans in Training (Aussie-FIT) men’s health behaviour change program: a protocol for a randomised controlled hybrid effectiveness–implementation trial
Authors: McDonald Matthew David , Brickley Bryce , Pavey Toby , Smith James A , Maiorana Andrew , McCaffrey Tracy , Hillis Graham , Bonson Jason , Chih Hui Jun , Gupta Himanshu , Holmes Scarlett , Hunt Kate , Kerr Deborah A , Kwaśnicka Dominika , Makate Marshall , McVeigh Joanne , Moullin Joanna C , Smith Brendan J , Wharton Lee , Wharton Neil , Quested Eleanor
Published: October 2023

Introduction

Improving physical activity (PA) and healthy eating is critical for primary and secondary prevention of cardiovascular disease (CVD). Behaviour change programmes delivered in sporting clubs can engage men in health behaviour change, but are rarely sustained or scaled-up post trial. Following the success of pilot studies of the Australian Fans in Training (Aussie-FIT) programme, a hybrid effectiveness–implementation trial protocol was developed. This protocol outlines methods to: (1) establish if Aussie-FIT is effective at supporting men with or at risk of CVD to sustain improvements in moderate-to-vigorous PA (primary outcome), diet and physical and psychological health and (2) examine the feasibility and utility of implementation strategies to support programme adoption, implementation and sustainment.

Methods and analysis

A pragmatic multistate/territory hybrid type 2 effectiveness–implementation parallel group randomised controlled trial with a 6-month wait list control arm in Australia. 320 men aged 35–75 years with or at risk of CVD will be recruited. Aussie-FIT involves 12 weekly face-to-face sessions including coach-led interactive education workshops and PA delivered in Australian Football League (Western Australia, Northern Territory) and rugby (Queensland) sports club settings. Follow-up measures will be at 3 and 6 months (both groups) and at 12 months to assess maintenance (intervention group only). Implementation outcomes will be reported using the Reach, Effectiveness, Adoption, Implementation, Maintenance framework.

Ethics and dissemination

This multisite study has been approved by the lead ethics committees in the lead site’s jurisdiction, the South Metropolitan Health Service Human Research Ethics Committee (Reference RGS4254) and the West Australian Aboriginal Health Ethics Committee (HREC1221). Findings will be disseminated at academic conferences, peer-reviewed journals and via presentations and reports to stakeholders, including consumers. Findings will inform a blueprint to support the sustainment and scale-up of Aussie-FIT across diverse Australian settings and populations to benefit men’s health.

Trial registration number

This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623000437662).