bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliable characterization of sound features in fishes begins in open-water environments
Authors: Banse Marine , Lecchini David , Bertucci Frédéric , Parmentier Eric
Published: July 2023

Many fishes use sounds to communicate in a wide range of behavioral contexts. In monitoring studies, these sounds can be used to detect and identify species. However, being able to confidently link a sound to the correct emitting species requires precise acoustical characterization of the signals in controlled conditions. For practical reasons, this characterization is often performed in small sized aquaria, which, however, may cause sound distortion, and prevents an accurate description of sound characteristics that will ultimately impede sound-based species identification in open-water environments. This study compared the sounds features of five specimens of the silverspot squirrelfish Sargocentron caudimaculatum recorded at sea and in aquaria of different sizes and materials. Our results point out that it is preferable to record fish sounds in an open-water environment rather than in small aquaria because acoustical features are affected (sound duration and dominant frequency) when sounds are recorded in closed environments as a result of reverberation and resonance. If not possible, it is recommended that (1) sound recordings be made in plastic or plexiglass aquaria with respect to glass aquaria and (2) aquaria with the largest dimensions and volumes be chosen.
Correlation-based passive localization: Linear system modeling and sparsity-aware optimization
Authors: Zhang Ting , Zhou Dongyao , Cheng Lei , Xu Wen
Published: July 2023

In underwater passive localization, matched field processing has faced mismatch challenges for many years. To overcome the mismatch, data-derived replicas have gained increasing popularity due to their better localization performance than parameter-based ones, among which the cross correlation–based replicas showed enhanced robustness against the spectral differences between the library and target vessels. However, cross correlation–based matching localizations result in high sidelobes and require enough frequency samples to eliminate grating lobes. This issue has been widely reported in the previous literature but has yet to be theoretically analyzed. In this work, we revisit the conventional correlation-based matching procedures and formulate the ambiguity surface as a least-norm solution of an underdetermined linear system. This formulation permits understanding the sidelobes from an optimization perspective. Based on this view, the high sidelobe challenge and requirement of measurements are systematically tackled by recasting the matching problem as a sparsity-aware optimization problem. The superiority of the proposed optimization approach is showcased through simulated data in the waveguide, microphone data in the air, and SWellEx-96 data. The linear system modeling is also extended to a distributed sensor network, profiting from the spatial gain brought by various azimuthal directions with respect to the source.
National Collegiate Athletic Association Division I Assistant Coaches’ Understanding and Use of Mental Performance and Mental Health Services
Authors: Eckenrod Morgan R. , Hill Heather , Thompson Melissa , Neelis Laurie A. , Donahue Paul T.
Published: July 2023

Assistant coaches play an important role in National Collegiate Athletic Association (NCAA) athletic departments and spend substantial amounts of time working with student-athletes, yet no research to date has examined their knowledge of mental performance and mental health services. Therefore, the purpose of this study was to learn about NCAA Division I assistant coaches’ understanding and use of mental performance and mental health services. Thirteen assistant coaches employed at universities with at least one mental performance consultant and one licensed mental health provider were interviewed. Thematic analysis procedures were used, and five themes were constructed: (a) day-to-day responsibilities of the assistant coach, (b) needing both mental performance and mental health services, (c) factors influencing understanding of mental performance and mental health services, (d) factors impacting student-athlete utilization of mental performance and mental health services, and (e) confusion between mental performance and mental health services.
Single-dose injectable nanovaccine-in-hydrogel for robust immunotherapy of large tumors with abscopal effect
Authors: Cheng Furong , Su Ting , Zhou Shurong , Liu Xiang , Yang Suling , Lin Shuibin , Guo Weisheng , Zhu Guizhi
Published: July 2023

Current cancer immunotherapy [e.g., immune checkpoint blockade (ICB)] only benefits small subsets of patients, largely due to immunosuppressive tumor microenvironment (TME). In situ tumor vaccination can reduce TME immunosuppression and thereby improve cancer immunotherapy. Here, we present single-dose injectable (nanovaccines + ICBs)-in-hydrogel (NvIH) for robust immunotherapy of large tumors with abscopal effect. NvIH is thermo-responsive hydrogel co-encapsulated with ICB antibodies and novel polymeric nanoparticles loaded with three immunostimulatory agonists for Toll-like receptors 7/8/9 (TLR7/8/9) and stimulator of interferon genes (STING). Upon in situ tumor vaccination, NvIH undergoes rapid sol-to-gel transformation, prolongs tumor retention, sustains the release of immunotherapeutics, and reduces acute systemic inflammation. In multiple poorly immunogenic tumor models, single-dose NvIH reduces multitier TME immunosuppression, elicits potent TME and systemic innate and adaptive antitumor immunity with memory, and regresses both local (vaccinated) and distant large tumors with abscopal effect, including distant orthotopic glioblastoma. Overall, NvIH holds great potential for tumor immunotherapy.
Reversible phase separation of ESCRT protein ALIX through tyrosine phosphorylation
Authors: Elias Ruben D. , Zhu Yingqi , Su Qi , Ghirlando Rodolfo , Zhang Jin , Deshmukh Lalit
Published: July 2023

Cytokinetic abscission, the last step of cell division, is regulated by the ESCRT machinery. In response to mitotic errors, ESCRT proteins, namely, ALIX, CHMP4B, and CHMP4C, accumulate in the cytosolic compartments termed “abscission checkpoint bodies” (ACBs) to delay abscission and prevent tumorigenesis. ALIX contributes to the biogenesis and stability of ACBs via an unknown mechanism. We show that ALIX phase separates into nondynamic condensates in vitro and in vivo, mediated by the amyloidogenic portion of its proline-rich domain. ALIX condensates confined CHMP4 paralogs in vitro. These condensates dissolved and reformed upon reversible tyrosine phosphorylation of ALIX, mediated by Src kinase and PTP1B, and sequestration of CHMP4C altered their Src-mediated dissolution. NMR analysis revealed how ALIX triggers the activation of CHMP4 proteins, which is required for successful abscission. These results implicate ALIX’s phase separation in the modulation of ACBs. This study also highlights how posttranslational modifications can control protein phase separation.
Pressure-driven distillation using air-trapping membranes for fast and selective water purification
Authors: Nguyen Duong T. , Lee Sangsuk , Lopez Kian P. , Lee Jongho , Straub Anthony P.
Published: July 2023

Membrane technologies that enable the efficient purification of impaired water sources are needed to address growing water scarcity. However, state-of-the-art engineered membranes are constrained by a universal, deleterious trade-off where membranes with high water permeability lack selectivity. Current membranes also poorly remove low–molecular weight neutral solutes and are vulnerable to degradation from oxidants used in water treatment. We report a water desalination technology that uses applied pressure to drive vapor transport through membranes with an entrapped air layer. Since separation occurs due to a gas-liquid phase change, near-complete rejection of dissolved solutes including sodium chloride, boron, urea, and
N
-nitrosodimethylamine is observed. Membranes fabricated with sub-200-nm-thick air layers showed water permeabilities that exceed those of commercial membranes without sacrificing salt rejection. We also find the air-trapping membranes tolerate exposure to chlorine and ozone oxidants. The results advance our understanding of evaporation behavior and facilitate high-throughput ultraselective separations.
Structural basis for the ubiquitination of G protein βγ subunits by KCTD5/Cullin3 E3 ligase
Authors: Jiang Wentong , Wang Wei , Kong Yinfei , Zheng Sanduo
Published: July 2023

G protein–coupled receptor (GPCR) signaling is precisely controlled to avoid overstimulation that results in detrimental consequences. Gβγ signaling is negatively regulated by a Cullin3 (Cul3)–dependent E3 ligase, KCTD5, which triggers ubiquitination and degradation of free Gβγ. Here, we report the cryo–electron microscopy structures of the KCTD5-Gβγ fusion complex and the KCTD7-Cul3 complex. KCTD5 in pentameric form engages symmetrically with five copies of Gβγ through its C-terminal domain. The unique pentameric assembly of the KCTD5/Cul3 E3 ligase places the ubiquitin-conjugating enzyme (E2) and the modification sites of Gβγ in close proximity and allows simultaneous transfer of ubiquitin from E2 to five Gβγ subunits. Moreover, we show that ubiquitination of Gβγ by KCTD5 is important for fine-tuning cyclic adenosine 3´,5´-monophosphate signaling of GPCRs. Our studies provide unprecedented insights into mechanisms of substrate recognition by unusual pentameric E3 ligases and highlight the KCTD family as emerging regulators of GPCR signaling.
Targeting and arginine-driven synergizing photodynamic therapy with nutritional immunotherapy nanosystems for combating MRSA biofilms
Authors: Zhang Aoxue , Wu Hao , Chen Xin , Chen Zhen , Pan Yuanhu , Qu Wei , Hao Haihong , Chen Dongmei , Xie Shuyu
Published: July 2023

The resistance and immune escape of methicillin-resistant
Staphylococcus aureus
(MRSA) biofilms cause recalcitrant infections. Here, we design a targeting and synergizing cascade PDT with nutritional immunotherapy nanosystems (Arg-PCN@Gel) containing PCN-224 as PDT platform for providing reactive oxygen species (ROS), incorporating arginine (Arg) as nitric oxide (NO) donor to cascade with ROS to produce more lethal ONOO
−
and promote immune response, and coating with gelatin as targeting agent and persistent Arg provider. The nanosystems adhered to the autolysin of MRSA and inhibited Arg metabolism by down-regulating
icdA
and
icaA
. It suppressed polysaccharide intercellular adhesin and extracellular DNA synthesis to prevent biofilm formation. The NO broke mature biofilms and helped ROS and ONOO
−
penetrate into biofilms to inactivate internal MRSA. Arg-PCN@Gel drove Arg to enhance immunity via inducible NO synthase/NO axis and arginase/polyamine axis and achieve efficient target treatment in MRSA biofilm infections. The targeting and cascading PDT synergized with nutritional immunotherapy provide an effective promising strategy for biofilm-associated infections.
Self-powered enzyme-linked microneedle patch for scar-prevention healing of diabetic wounds
Authors: Zhang Xiangli , Wang Zhilong , Jiang Hong , Zeng Huajing , An Nan , Liu Bin , Sun Luyi , Fan Zengjie
Published: July 2023

Diabetic wounds with complex pathological features and a difficult-to-heal nature remain a formidable challenge. To address this challenge, we design and fabricate a self-powered enzyme-linked microneedle (MN) patch composed of anode and cathode MN arrays, which respectively contain glucose oxidase (GOx) and horseradish peroxidase (HRP) encapsulated in ZIF-8 nanoparticles. The enzymatic cascade reaction in the MN patch can effectively reduce local hyperglycemia in diabetic wounds while generating stable microcurrents to promote rapid healing of diabetic wounds. Therefore, the diabetic wounds treated with this MN patch exhibit rapid, complete, and scar-preventative healing, which can be attributed to the synergistic actions of hypoglycemic, antibacterial, anti-inflammatory, and bioelectrical stimulation. In brief, the self-powered MN patch is an effective method to rapidly promote diabetic wound healing and prevent scar formation.
Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice
Authors: Schwarz Madeline M. , Ganaie Safder S. , Feng Annie , Brown Griffin , Yangdon Tenzin , White J. Michael , Hoehl Ryan M. , McMillen Cynthia M. , Rush Rachael E. , Connors Kaleigh A. , Cui Xiaoxia , Leung Daisy W. , Egawa Takeshi , Amarasinghe Gaya K. , Hartman Amy L.
Published: July 2023

Rift Valley fever virus (RVFV) is an emerging arbovirus found in Africa. While RVFV is pantropic and infects many cells and tissues, viral replication and necrosis within the liver play a critical role in mediating severe disease. The low-density lipoprotein receptor–related protein 1 (Lrp1) is a recently identified host factor for cellular entry and infection by RVFV. The biological significance of Lrp1, including its role in hepatic disease in vivo, however, remains to be determined. Because Lrp1 has a high expression level in hepatocytes, we developed a mouse model in which Lrp1 is specifically deleted in hepatocytes to test how the absence of liver Lrp1 expression affects RVF pathogenesis. Mice lacking Lrp1 expression in hepatocytes showed minimal RVFV replication in the liver, longer time to death, and altered clinical signs toward neurological disease. In contrast, RVFV infection levels in other tissues showed no difference between the two genotypes. Therefore, Lrp1 is essential for RVF hepatic disease in mice.
Emergence of
Phytobacter diazotrophicus
carrying an IncA/C
2
plasmid harboring
bla
NDM-1
in Tokyo, Japan
Authors: Kubota Hiroaki , Nakayama Tomohiro , Ariyoshi Tsukasa , Uehara Satomi , Uchitani Yumi , Tsuchida Sachio , Nishiyama Hiroyuki , Morioka Ichiro , Koshinaga Tsugumichi , Kusabuka Akiko , Nakatsubo Naoki , Yamagishi Takuya , Tabuchi Yuri , Okuno Rumi , Kobayashi Kai , Mitobe Morika , Yokoyama Keiko , Shinkai Takayuki , Suzuki Jun , Sadamasu Kenji
Published: July 2023

Phytobacter diazotrophicus
is an Enterobacterales species that was originally identified as a plant growth-promoting, Gram-negative bacterium. Recently, this species has been recognized as relevant to opportunistic human and nosocomial infections in clinical settings. Its frequent misidentification as other Enterobacterales species from clinical examination occasionally causes a delay in the identification of nosocomial outbreaks. Here, we report the emergence of New Delhi metallo-β-lactamase (NDM)-producing
P. diazotrophicus
isolated from hospitalized pediatric patients and hospital environments in Tokyo, Japan. In our case, these isolates were found during an investigation of carbapenem-resistant Enterobacterales in relation to nosocomial infections. Whole-genome sequencing is useful for overcoming the difficulty of species identification. Furthermore, we found that
bla
NDM-1
was carried by an IncA/C
2
plasmid (approximately 170 kbp), which was transferrable from the clinical isolates to the recipient strain
Escherichia coli
J53. Our study demonstrated that
P. diazotrophicus
behaves as a carrier of
bla
NDM
-harboring plasmids, potentially disseminating resistance to carbapenems among Enterobacterales.

IMPORTANCE

Early detection of nosocomial outbreaks is important to minimize the spread of bacteria. When an outbreak is caused by multidrug-resistant bacteria such as carbapenem-resistant Enterobacterales, a delay in findings makes it difficult to control it because such bacteria often spread not only among human patients but also in hospital environments.
Phytobacter diazotrophicus
, an Enterobacterales species that has recently been found to be relevant to clinical settings, is often misidentified as other bacteria in clinical laboratories. Here, we found NDM-producing
P. diazotrophicus
in hospitalized pediatric patients and their environment in Tokyo, Japan. Given that the isolates carried
bla
NDM-1
-harboring transferrable plasmids, the influence of such bacteria could be greater with the mediation of horizontal transfer of carbapenem resistance. Our findings suggest that
P. diazotrophicus
should be recognized as an NDM-carrier, for which more attention should be paid in clinical settings.
Supplemental Material: Rapid fluvial remobilization of sediments deposited by the 2021 Chamoli disaster, Indian Himalaya
Authors: Westoby Matthew J , al et.
Published: July 2023

Additional methodological detail, field photographs, and modeling outputs. 
Fetal alcohol syndrome in the UK
Authors: Burleigh Charlotte Rebecca , Lynn Richard M , Verity Chris , Winstone Anne Marie , White Simon R , Johnson Kathryn
Published: July 2023

Objective

To determine the incidence of fetal alcohol syndrome (FAS) in the UK in children aged 0–16 years.

Design

Active surveillance was undertaken through the British Paediatric Surveillance Unit between October 2018 and October 2019 inclusive. Data were collected from reporting clinicians using standardised questionnaires.

Patients

Children aged 0–16 years in the UK and Ireland with a diagnosis of FAS seen in the previous month. This study did not include children with fetal alcohol spectrum disorder.

Main outcome measures

Demographic details (including age and ethnicity), details of exposure, growth parameters, neurological and cognitive diagnoses, and service usage.

Results

148 notifications were received. After exclusions and withdrawals, there were 10 confirmed and 37 probable cases (analysed together). Just 24 of these children were newly diagnosed with FAS during the surveillance period, giving an estimated incidence rate of 3.4/100 000 live births (95% CI 2.2 to 5.0); their median age at diagnosis was just over 5 years and they were diagnosed between 3 months and 14 years 3 months of age.

Conclusions

The estimated incidence rate of FAS is lower than reported by similar studies and there was a wide variation in the age that cases were diagnosed. This, combined with the fact that many cases were notified and then withdrawn or excluded, suggests that in the UK there is a lack of consistency and certainty in diagnosing FAS. The study findings strongly support the need to educate key professionals involved in the care of infants and children at risk of FAS.
Randomised control trial of oxygen assist module in preterm infants on high-flow nasal cannula support
Authors: Nair Vrinda , Kannan Loganathan Prakash , Lal Mithilesh Kumar , Bachman Thomas Edward , Fantl Ron
Published: July 2023

Objective

To evaluate the efficacy of automatic oxygen control (A-FiO2) in reducing the extremes of oxygen saturations (SpO2<80% and SpO2>98%) in preterm infants on high-flow nasal cannula (HFNC) respiratory support using Vapotherm Precision Flow.

Design

A parallel-arm randomised controlled trial.

Setting

A level-III neonatal intensive care unit.

Patients

Preterm infants born <33 (23+0 to 32+6) weeks receiving HFNC as respiratory support.

Interventions

A-FiO2versus manual (M-FiO2) oxygen control during the full course of HFNC support.

Outcomes

The primary outcome of this study is percentage of time spent in extreme oxygen saturations (<80% and >98%) in preterm infants when receiving HFNC as respiratory support. Secondary outcomes were time with SpO2between 90% and 95% plus time >95% without supplemental oxygen.

Results

60 infants were randomised equally to either A-FiO2or M-FiO2arm. Their baseline characteristics were comparable. They spent a median of 5.3 (IQR: 2.0–8.4) and 6.5 (IQR: 2.9–13.7) days in the study, A-FiO2and M-FiO2, respectively. The percentage of time spent in SpO2<80% (median of 0.4% (0.1%–0.8%) vs 1.6% (0.6%–2.6%), p=0.002) and >98% (median 0.2% (0.1%–0.9%) vs 1.9% (0.7%–4%), p<0.001) were significantly lower in A-FiO2compared with M-FiO2. The difference in median percentage of time in target range between the two arms was 26% (81% (74%–93%) in A-FiO2vs 55% (48%–72%) in M-FiO2).

Conclusion

A-FiO2was associated with statistically significant reduction in the percentage of time spent in extremes of saturation when compared with M-FiO2in preterm infants receiving HFNC.

Trial registration number

NCT04687618.
Scalability of mobile technology interventions in the prevention and management of HIV among adolescents in low-income and middle-income countries: protocol for a systematic review
Authors: Adebayo Emmanuel S , Wang Dongqing , Olaniyan Halimat Omowumi , Olumide Adesola Oluwafunmilola , Ogunniyi Adesola , Fawzi Wafaie
Published: July 2023

Introduction

The rate of new infections with HIV remains high among adolescents globally. Adolescents in low-income and middle-income countries (LMICs), who are least likely to have access to quality healthcare, have the highest proportion of those living with HIV. Mobile technology has played an important role in providing access to information and services among adolescents in recent years. This review aims to synthesise and summarise information that will be useful in the planning, designing and implementing of future mHealth strategies.

Methods and analysis

Interventional studies, reported in English, on the prevention and management of HIV among adolescents that used mobile technology in LMICs will be included. MEDLINE (via PubMed), Embase, Web of Science, CINAHL, Clinicaltrials.gov, WHO International Clinical Trials Registry Platform (ICTRP), and the Cochrane Library are the information sources that have been identified as relevant to the area of study. These sources will be searched from inception to March 2023. The risk of bias will be assessed using the Cochrane Risk of Bias tool. The scalability of each study will be assessed using the Intervention Scalability Assessment Tool. Two independent reviewers will conduct the selection of studies, data extraction, and assessment of the risk of bias and scalability. A narrative synthesis of all the included studies will be done.

Ethics and dissemination

Ethical approval was not necessary for this study. This is a systematic review of publicly available information and therefore ethical approval was not deemed necessary. The results of this review will be published in a peer reviewed journal.

Trial registration

This protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42022362130.
Establishing internationally accepted conceptual and operational definitions of social prescribing through expert consensus: a Delphi study
Authors: Muhl Caitlin , Mulligan Kate , Bayoumi Imaan , Ashcroft Rachelle , Godfrey Christina
Published: July 2023

Objective

The aim of this study was to establish internationally accepted conceptual and operational definitions of social prescribing.

Design

A three-round Delphi study was conducted.

Setting

This study was conducted virtually using an online survey platform.

Participants

This study involved an international, multidisciplinary panel of experts. The expert panel (n=48) represented 26 countries across five continents, numerous expert groups and a variety of years of experience with social prescribing, with the average being 5 years (range=1–20 years).

Results

After three rounds, internationally accepted conceptual and operational definitions of social prescribing were established. The definitions were transformed into the Common Understanding of Social Prescribing (CUSP) conceptual framework.

Conclusion

This foundational work offers a common thread—a shared sense of what social prescribing is, which may be woven into social prescribing research, policy and practice to foster common understanding of this concept.
Motor and autonomic concomitant health improvements with neuromodulation and exercise (MACHINE) training: a randomised controlled trial in individuals with spinal cord injury
Authors: Shackleton Claire , Samejima Soshi , Williams Alison MM , Malik Raza N , Balthazaar Shane JT , Alrashidi Abdullah , Sachdeva Rahul , Elliott Stacy L , Nightingale Thomas E , Berger Michael J , Lam Tania , Krassioukov Andrei V
Published: July 2023

Introduction

Motor and autonomic dysfunctions are widespread among people with spinal cord injury (SCI), leading to poor health and reduced quality of life. Exercise interventions, such as locomotor training (LT), can promote sensorimotor and autonomic recovery post SCI. Recently, breakthroughs in SCI research have reported beneficial effects of electrical spinal cord stimulation (SCS) on motor and autonomic functions. Despite literature supporting the independent benefits of transcutaneous SCS (TSCS) and LT, the effect of pairing TSCS with LT is unknown. These therapies are non-invasive, customisable and have the potential to simultaneously benefit both sensorimotor and autonomic functions. The aim of this study is to assess the effects of LT paired with TSCS in people with chronic SCI on outcomes of sensorimotor and autonomic function.

Methods and analysis

Twelve eligible participants with chronic (>1 year) motor-complete SCI, at or above the sixth thoracic segment, will be enrolled in this single-blinded, randomised sham-controlled trial. Participants will undergo mapping for optimisation of stimulation parameters and baseline assessments of motor and autonomic functions. Participants will then be randomly assigned to either LT+TSCS or LT+Sham stimulation for 12 weeks, after which postintervention assessments will be performed to determine the effect of TSCS on motor and autonomic functions. The primary outcome of interest is attempted voluntary muscle activation using surface electromyography. The secondary outcomes relate to sensorimotor function, cardiovascular function, pelvic organ function and health-related quality of life. Statistical analysis will be performed using two-way repeated measures Analysis of variance (ANOVAs) or Kruskal-Wallis and Cohen’s effect sizes.

Ethics and dissemination

This study has been approved after full ethical review by the University of British Columbia’s Research Ethics Board. The stimulator used in this trial has received Investigation Testing Authorisation from Health Canada. Trial results will be disseminated through peer-reviewed publications, conference presentations and seminars.

Trial registration number

NCT04726059.
Effectiveness of laparoscopic niche resection versus expectant management in patients with unexplained infertility and a large uterine caesarean scar defect (uterine niche): protocol for a randomised controlled trial (the LAPRES study)
Authors: Vissers Jolijn , Klein Meuleman Saskia J M , de Leeuw Robert A , van Eekelen Rik , Groenman Freek A , Mol Ben W , Hehenkamp Wouter J K , Huirne Judith A F
Published: July 2023

Introduction

A uterine niche is a defect at the site of the uterine caesarean scar that is associated with gynaecological symptoms and infertility. Promising results are reported in cohort studies after a laparoscopic niche resection concerning reduction of gynaecological symptoms in relation to baseline and concerning pregnancy outcomes. However, randomised controlled trials to study the effect of a laparoscopic niche resection on reproductive outcomes in infertile women are lacking. This study will answer the question if laparoscopic niche resection in comparison to expectant management improves reproductive outcomes in infertile women with a large uterine niche.

Methods and analysis

The LAPRES study is a randomised, non-blinded, controlled trial, including 200 infertile women with a total follow-up of 2 years. Women with the presence of a large niche in the uterine caesarean scar and unexplained infertility of at least 1 year or failed IVF will be randomly allocated to a laparoscopic niche resection within 6 weeks or to expectant management for at least 9 months. A large niche is defined as a niche with a depth of >50% of the myometrial thickness and a residual myometrium of ≤3 mm on transvaginal ultrasound. Those receiving expectant management will be allowed to receive fertility therapies, including assisted reproductive techniques, if indicated. The primary outcome is time to ongoing pregnancy, defined as a viable intrauterine pregnancy at 12 weeks’ gestation. Secondary outcome measures are time to conception leading to a live birth, other pregnancy outcomes, received fertility therapies after randomisation, menstruation characteristics, patient satisfaction, quality of life, additional interventions, and surgical and ultrasound outcomes (intervention group). Questionnaires will be filled out at baseline, 6, 12 and 24 months after randomisation. Ultrasound evaluation will be performed at baseline and at 3 months after surgery.

Ethics and dissemination

The study protocol was approved by the medical ethics committee of the Amsterdam University Medical Centre. (Ref. No. 2017.030). Participants will sign a written informed consent before participation. The results of this study will be submitted to a peer-reviewed journal for publication.

Trial registration number: Dutch Trial Register (ref. no. NL6350http://www.trialregister.nl).
Effect of neurosurgical high observation beds (HOBs) on service provision: a single-centre experience and cost analysis
Authors: Crispi Vassili , Bolton William , Town Rebecca , Anderson Ian
Published: July 2023

Objective

To evaluate the effect of level 1, high observation beds (HOBs) compared with high dependency unit (HDU) and neurosurgical intensive care unit (NICU) admission on service provision, such as cancelled operations, and healthcare costs.

Methods

A retrospective, observational, single-centre cross-sectional study at a single, large UK neurosurgical centre. All adult patients admitted to neurosurgical HOBs between December 2021 and July 2022 were included. The list of cancelled procedures was collected from 2019 to 2022. To evaluate the impact of admission of eligible patients to HOBs, the total bed days, cost per bed day, number of admissions and cost per admission were obtained for all clinical areas the financial years 2019/2020 and 2021/2022.

Results

307 patients were included in the study: 59.7% of HOBs admissions were elective and 37.7% were acute; admissions were for cranial procedures or conservative treatment (64.8%), spinal (32.6%) or other (2.6%). Following admission, 73.3% of patients were stepped down to the ward prior to discharge home. Only seven patients required escalation to level-2 or level-3 care. Overall, 97% of all HOBs patients were discharged home at the end of hospital stay. Occupancy rate was 90.4%.

The cost of bed day increased from ward, level 0 (£384), then level 1 (£376), to level 2 (£787–1211) and to level 3 (£1628). From 2019 to 2021, 558 operations had been cancelled, and 140 (37.8%) of 370 were estimated to have been potentially avoided by HOBs admissions due to conflict of scheduling, ward bed capacity and critical care bed capacity. In addition, a minimum total expenditure due to cancelled operations was estimated at £22 923.50 yearly on average.

Conclusion

This study recognises HOBs growing role in the management of acutely unwell patients in ward-based environments. While recognising the associated challenges, this study highlighted the potential in reducing healthcare costs. Further studies should evaluate the impact and limitations of HOBs on patients’ recovery and outcomes, compared to HDU and NICU.
Barriers, facilitators and implementation strategies for guideline-adherence in physiotherapy: a scoping review protocol
Authors: Reiter Nils L , Rosen Diane , Erhart Michael , Vogel Barbara
Published: July 2023

Introduction

Guideline-adherent physiotherapy can improve patient outcomes and reduce costs in the healthcare system. However, although there are numerous guidelines for physiotherapy practice, services are not consistently based on clinical practice guidelines. While various systematic and scoping reviews have highlighted barriers, facilitators and implementation strategies for guideline-adherent practice in other health professions, this scoping review aims to explore the barriers and facilitators for guideline-adherent physiotherapy and summarises the strategies used to implement such practice.

Methods and analysis

This scoping review will be based on Arksey and O’Malley’s scoping review methodology and the methodological guidance for conducting scoping reviews published by Joanna Briggs Institute. Relevant publications will be first searched from the beginning of June 2023 on the MEDLINE and CINAHL databases before we expand the search to other databases such as EMBASE, the Cochrane Library and PEDro at the end of June 2023. Two reviewers will independently screen the titles and abstracts of all retrieved citations for inclusion against the eligibility criteria before conducting an independent full-text screening. The criteria will be tested on a sample of abstracts before beginning the abstract review to ensure that they are robust enough to capture any articles that may relate. The extracted data will finally be collated and charted to summarise key findings regarding our research question.

Ethics and dissemination

This scoping review will provide an extensive overview of the barriers, facilitators and implementation strategies for guideline-adherent physiotherapy. As scoping reviews are a form of secondary data analysis, ethical review is not required. Results will be disseminated through a peer-reviewed publication and stakeholder meetings.

Trial registration number

This scoping review has been registered on 3 April 2023 on the Open Science Framework underhttps://doi.org/10.17605/OSF.IO/SEUW6.
Drug survival and safety of biosimilars and originator adalimumab in the treatment of psoriasis: a multinational cohort study
Authors: Phan Duc Binh , Jourdain Hugo , González-Quesada Alicia , Zureik Mahmoud , Rivera-Díaz Raquel , Sahuquillo-Torralba Antonio , Descalzo-Gallego Miguel Angel , Lunt Mark , Garcia-Doval Ignacio , Sbidian Emilie , Warren R B , Yiu Zenas Z N
Published: July 2023

Introduction

Psoriasis is a chronic inflammatory skin disease. Adalimumab is an effective but previously expensive biological treatment for psoriasis. The introduction of biosimilars following the patent expiry of the originator adalimumab Humira has reduced the unit cost of treatment. However, the long-term effectiveness and safety of adalimumab biosimilars for treating psoriasis in real-world settings are uncertain and may be a barrier to widespread usage.

Methods and analysis

This study aims to compare the drug survival and safety of adalimumab biosimilars to adalimumab originator for the treatment of psoriasis. We will use both routinely collected healthcare databases and dedicated pharmacovigilance registries from the PsoNet initiative, including data from the UK, France and Spain. We will conduct a cohort study using a prevalent new user design. We will match patients on previous adalimumab exposure time to create two equal-sized cohorts of biosimilar and originator users. The coprimary outcomes are drug survival, defined by the time from cohort entry to discontinuation of the drug of interest; and risk of serious adverse events, defined by adverse events leading to hospitalisation or death. Cox proportional hazards models will be fitted to calculate HRs as the effect estimate for the outcomes.

Ethics and dissemination

The participating registries agree with the Declaration of Helsinki and received approval from local ethics committees. The results of the study will be published in scientific journals and presented at international dermatology conferences by the end of 2023.
Multimorbidity due to novel pathogenic variants in theWFS1/RP1/NOD2genes: autosomal dominant congenital lamellar cataract, retinitis pigmentosa and Crohn’s disease in a British family
Authors: Berry Vanita , Ionides Alexander , Georgiou Michalis , Quinlan Roy A , Michaelides Michel
Published: July 2023

Background

A five generation family has been analysed by whole exome sequencing (WES) for genetic associations with the multimorbidities of congenital cataract (CC), retinitis pigmentosa (RP) and Crohn’s disease (CD).

Methods

WES was performed for unaffected and affected individuals within the family pedigree followed by bioinformatic analyses of these data to identify disease-causing variants with damaging pathogenicity scores.

Results

A novel pathogenic missense variant inWFS1: c.1897G>C; p.V633L, a novel pathogenic nonsense variant inRP1: c.6344T>G; p.L2115* and a predicted pathogenic missense variant inNOD2: c.2104C>T; p.R702W are reported. The three variants cosegregated with the phenotypic combinations of autosomal dominant CC, RP and CD within individual family members.

Conclusions

Here, we report multimorbidity in a family pedigree listed on a CC register, which broadens the spectrum of potential cataract associated genes to include bothRP1andNOD2.
Intravitreal anti-vascular endothelial growth factor for the treatment of chronic central serous retinopathy: a meta-analysis of the literature
Authors: Palakkamanil Mathew , Munro Monique , Sethi Abhishek , Adatia Feisal
Published: July 2023

Objective

The purpose of this study was to evaluate the role of anti-vascular endothelial growth factor (anti-VEGF) treatment on the functional and structural parameters of chronic central serous retinopathy (CSR).

Methods

PubMed was used to systematically review literature published from 1 January 2009 to 1 July 2022. Studies were included if patients in their cohort had symptoms for more than 3 months, anti-VEGF treatment was provided and the following outcomes were reported: best-corrected visual acuity (BCVA), central macular thickness (CMT) and proportion of subretinal fluid (SRF) resolution.

Results

339 eyes met inclusion criteria with a mean patient age of 45.8±4.9 years. The weighted mean baseline BCVA for the 20 studies was 0.39±0.23 logMAR, which improved to 0.28±0.24 after treatment with anti-VEGF injections (p=0.069). The weighted baseline CMT for the 20 studies decreased from 395.2±52.0 µm to 243.0±41.9 µm (p<0.001). The weighted overall percentage of SRF resolution was 68.4%.

Conclusion

Anti-VEGF treatment demonstrated significantly decreased macular thickness and resolution of SRF in the treatment of chronic CSR without any reported adverse effects. However, BCVA did not significantly improve with pharmacotherapy.
Occurrence of uveitis in a population-based cohort of inflammatory bowel diseases followed for 10 years: an observational study
Authors: Granstam Elisabet , Rönnblom Anders
Published: July 2023

Objective

The coexistence of inflammatory bowel diseases (IBDs) and uveitis has been known for 100 years. The reported frequency by which these conditions appear in the same patient has varied considerably. The aim of this study was to investigate the occurrence of uveitis in a well-defined population-based cohort of patients with IBD including all age groups and followed for at least 10 years.

Method and analysis

All newly diagnosed patients with ulcerative colitis and Crohn’s disease in the county of Uppsala between 2005 and 2009 were prospectively followed. At the end of 2022, the medical notes were checked and all contacts with the healthcare system regarding ocular symptoms were scrutinised.

Results

A total of 330 patients with ulcerative colitis and 153 patients with Crohn’s disease were included in the cohort. Four hundred and forty-two of these (91.5%) could be followed for 10 years or until death. Thirteen patients with ulcerative colitis were affected by uveitis (3.9%), and one of the patients with Crohn’s disease (0.7%). Most often the uveitis was diagnosed after the bowel disease (median 8.9 years, 7.7 years SD).

Conclusion

Low occurrence of uveitis was identified in the IBD population. All affected individuals except one were diagnosed with ulcerative colitis. Most of the patients had their eye disease around 10 years later than their IBD diagnosis. It is suggested that systemic anti-inflammatory treatment for the IBD protects against intraocular inflammation in this cohort.
Constructing appropriate bioprinting regulations: the ethical importance of recognising a liminal technology
Authors: Moss Megan Frances
Published: July 2023

This article provides an analysis of bioprinting personalised medical device technology and its ethical challenges to regulation and research ethics. I argue the inclusion of bioprinting applications within existing regulatory frameworks does not adequately address the technologies disruption to the traditionally siloed activities of research and treatment. Using the conceptual framework of liminality, I offer a meaningful way to engage with this technology and address some identified concerns with how it will be categorised and the appropriate recognition of its evidentiary thresholds. I demonstrate these concerns through the exploration of limited conventional research methodologies tasked with the production of generalisable knowledge, specifically population-based evidence that is derived from Randomised Clinical Trials. I use Australian regulatory amendments introduced in 2021 as an example of current regulatory trajectories and highlight why I believe this approach to be insufficient. The significance of this argument will be to demonstrate the disruption of bioprinting applications to current approaches in medical policy, and how various jurisdictions are enacting regulation that is not fit for purpose.
Rights and duties of genetic counsellors in Germany related to relatives at risk: comparative thoughts on the German Genetic Diagnostics Act
Authors: Schneider Susanne A , Schneider Uwe H
Published: July 2023

Genetic testing has familial implications. Counsellors find themselves in (moral) conflict between medical confidentiality (towards the patient) and a potential right or even duty to warn at-risk relatives. Legal regulations vary between countries. English literature about German law is scarce. We reviewed the literature of relevant legal cases, focussing on German law, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This article aims to familiarise counsellors with their responsibilities, compare the situation between countries and point out legally unresolved areas.

According to the German Genetic Diagnostics Act (Gendiagnostikgesetz) in case of an ‘avoidable or treatable’ genetic disorder, geneticists ought to confine themselves to the obligated advice to the patient. Whether a breach of the duty of confidentiality can be justified in exceptional cases by ‘necessity as justification’ for actively informing relatives at risk remains legally unclear. In case of a ‘neither avoidable nor treatable’ genetic disease, geneticists should also refrain from actively informing relatives as the justifiable state of emergency does not permit to break the duty of confidentiality.
Pathogenic role of anti-cN1A autoantibodies in sporadic inclusion body myositis
Authors: Yamashita Satoshi , Tawara Nozomu , Zhang Ziwei , Nakane Shunya , Sugie Kazuma , Suzuki Naoki , Nishino Ichizo , Aoki Masashi
Published: July 2023

Background

Sporadic inclusion body myositis (sIBM) is an intractable muscle disease that frequently affects elderly people. Autoantibodies recognising cytosolic 5’-nucleotidase 1A (cN1A) were found in the sera of patients with sIBM. However, the pathogenic role of the autoantibodies remained unknown. This study investigated the pathogenic properties of the autoantibodies using active cN1A peptides immunisation.

Methods

Wild-type C57BL6 mice were injected with three different mouse cN1A peptides corresponding to the previously reported epitope sequences of human cN1A. After confirming the production of autoantibodies to the corresponding cN1A peptides in each group, changes in body weight, exercise capacity by treadmill test and histological changes in mice injected with cN1A peptides or controls were investigated.

Results

Autoantibodies against cN1A were detected in serum samples from mice injected with cN1A peptide. Some groups of mice injected with cN1A peptide showed significant weight loss and decreased motor activity. The number of myofibres with internal nuclei increased in all the peptide-injected groups, with surrounding or invading CD8-positive T cells into myofibres, abnormal protein aggregates and overexpression of p62 and LC3.

Conclusions

Active cN1A peptide immunisation partially reproduced the clinical and histological aspects of sIBM in wild-type mice. The murine model demonstrates the pathogenic properties of anti-cN1A autoantibodies to cause sIBM-like histological changes.
Microvascular damage in autoimmune connective tissue diseases: a capillaroscopic analysis from 20 years of experience in a EULAR training and research referral centre for imaging
Authors: Hysa Elvis , Pizzorni Carmen , Sammorì Silvia , Gotelli Emanuele , Cere Andrea , Schenone Carlotta , Ferrari Giorgia , Campitiello Rosanna , Gerli Veronica , Paolino Sabrina , Sulli Alberto , Smith Vanessa , Cutolo Maurizio
Published: July 2023

Objective

Nailfold videocapillaroscopy (NVC) allows the detection of microvascular damage in autoimmune connective tissue diseases (CTDs). The prevalence of the morphological capillary findings was retrospectively evaluated in a wide cohort of patients with Raynaud’s phenomenon secondary to a CTD at the time of the first single NVC, independently from their current treatment, autoantibody profile and comorbidities.

Methods

One-thousand-one-hundred-eighty-one patients affected by CTDs were included from 2001 to 2021. The considered CTDs were systemic sclerosis (SSc), undifferentiated connective tissue disease (UCTD), mixed connective tissue disease (MCTD), dermatomyositis (DM), systemic lupus erythematosus, Sjögren’s syndrome and primary antiphospholipid syndrome (aPS). The capillaroscopic parameters were distinguished between scleroderma patterns and non-scleroderma patterns.

Results

Giant capillaries were significantly more frequent in SSc, DM and MCTD than in other CTDs (respectively, in 73%, 73% and 61% of patients, p<0.001 when comparing each rate vs the other CTDs). The mean capillary count was significantly lower in SSc, DM and MCTD (respectively, 7.04±0.18 vs 6.5±0.75 vs 7.7±2 capillaries/linear mm) compared with the other CTDs (p<0.001 for each rate vs the other CTDs). The non-specific abnormalities of capillary morphology were significantly more frequent in SSc, MCTD and aPS (respectively, in 48%, 41% and 36% of cases, all p<0.001 vs each other CTDs).

Conclusion

This large size sample of patients with CTDs, collected over 20 years of analysis, confirms the highest prevalence of specific capillaroscopic alterations in patients with SSc, DM and MCTD, when compared with other CTDs.
Stability and Hawking-Page-like phase transition of phantom AdS black holes
Authors: Abdusattar Haximjan
Published: July 2023

In this work, we investigate the thermodynamic stability and phase structure of AdS black holes with either a Maxwell field (where we revisit past studies) or a phantom field. We conduct a comprehensive analysis of the free energy and temperature of these systems in both the canonical and grand canonical ensembles. Our findings reveal the occurrence of a phase transition in the grand canonical ensemble, resembling the Hawking-Page-like phase transition observed between the thermal radiation of AdS spacetime and thermodynamically stable large black holes. We present graphical representations of these phase transitions on free energy-temperature diagrams for the black holes. Completing our study, we obtain the transition temperature, minimum temperature and their dual relations.