bluuebunny/crossref_metadata_2025 huggingface dataset:
Monolayer calibration of endofullerenes with x-ray absorption from implanted keV ion doses
Authors: Lee Wei Chuang , Yu Lebin , Oscarsson Johan , Ochapski Michal W. , Sagehashi Ryunosuke , Zhang Yang , Popov Alexey A. , Gebeyehu Zewdu M. , Martini Leonardo , Forti Stiven , Coletti Camilla , Delley Bernard , Muntwiler Matthias , Primetzhofer Daniel , Greber Thomas
Published: January 2024

X-ray absorption spectroscopy (XAS) has the highest sensitivity for chemical element detection on surfaces. With this approach, small amounts of lanthanide-containing endofullerene molecules (Ho3N@C80) have been measured by total electron yield at a low flux bending magnet beamline. The monolayer coverage is calibrated by extrapolating the signals of constant doses (3×1014 cm−2) of Ho ions implanted into SiO2 with energies between 2 and 115 keV. At room temperature, the Ho XAS spectra of the molecules and implanted ions indicate trivalent but not identical Ho ground states. Still, this approach demonstrates a way for calibration of small coverages of molecules containing open core-shell elements.
Combining Heat and Altitude Training to Enhance Temperate, Sea-Level Performance
Authors: Girard Olivier , Peeling Peter , Racinais Sébastien , Périard Julien D.
Published: January 2024

Background: Repeated exposure to heat (ie, plasma volume expansion) or altitude (ie, increase in total hemoglobin mass), in conjunction with exercise, induces hematological adaptations that enhance endurance performance in each respective environment. Recently, combining heat and altitude training has become increasingly common for athletes preparing to compete in temperate, sea-level conditions. Purpose: To review the physiological adaptations to training interventions combining thermal and hypoxic stimuli and summarize the implications for temperate, sea-level performance. Current Evidence: To date, research on combining heat and hypoxia has employed 2 main approaches: simultaneously combining the stressors during training or concurrently training in the heat and sleeping at altitude, sometimes with additional training in hypoxia. When environmental stimuli are combined in a training session, improvements in aerobic fitness and time-trial performance in temperate, sea-level conditions are generally similar in magnitude to those observed with heat, or altitude, training alone. Similarly, training in the heat and sleeping at altitude does not appear to provide any additional hematological or nonhematological benefits for temperate; sea-level performance relative to training in hot, hypoxic, or control conditions. Conclusions: Current research regarding combined heat and altitude interventions does not seem to indicate that it enhances temperate, sea-level performance to a greater extent than “traditional” (heat or hypoxia alone) training approaches. A major challenge in implementing combined-stressor approaches lies in the uncertainty surrounding the prescription of dosing regimens (ie, exercise and environmental stress). The potential benefits of conducting heat and altitude exposure sequentially (ie, one after the other) warrants further investigation.
Why Should Athletes Brake Fast? Influence of Eccentric Velocity on Concentric Performance During Countermovement Jumps at Different Loads
Authors: Hernández-Davó Jose L. , Sabido Rafael , Omar-García Manuel , Boullosa Daniel
Published: January 2024

Purpose: The aim of the present study was to analyze the effect of different eccentric tempos on eccentric kinetics and kinematics and the subsequent concentric performance when performing countermovement jumps against different loads. Methods: After 1-repetition-maximum assessment and 2 familiarization sessions, 13 well-trained participants performed, in randomized order, 12 sets (4 tempos × 3 loads) of 4 repetitions of the loaded countermovement-jump exercise. The eccentric tempos analyzed were 5 and 2 seconds, as fast as possible, and accelerated (ie, without pause between repetitions), while the loads used were 30%, 50%, and 70% of 1-repetition maximum. Several kinetic and kinematic variables during both phases were recorded by linking a linear position transducer to the barbell. Results: The eccentric work was greater in the accelerated condition despite no changes in the eccentric depth. The peak and mean propulsive velocities were greater in the as-fast-as-possible and accelerated conditions. Correlation analysis showed that, compared with the 5-second condition, the increased concentric performance in the accelerated condition was related to the difference in eccentric work performed in the last 100 milliseconds of the eccentric phase (r > .770). Conclusions: Contrary to current practices, the current study highlights the need for performing the eccentric phase of loaded countermovement jumps, a common exercise performed by athletes for both training and evaluation purposes, as fast as possible. This allows not only a greater eccentric work but also improved concentric performance.
Individualizing Basketball-Specific Interval Training Using Anaerobic Speed Reserve: Effects on Physiological and Hormonal Adaptations
Authors: Wang Chenhang , Ye Mingliang
Published: January 2024

Purpose: We compared the adaptive responses to supramaximal high-intensity interval training (HIIT) individualized according to anaerobic speed reserve (ASR), the 30-15 Intermittent Fitness Test (VIFT), and velocity associated with maximum oxygen uptake (MAS) to determine which approach facilitates more identical adaptations across athletes with different profiles. Methods: Thirty national-level basketball players (age = 28.4 [5] y; body mass = 88.9 [6.3] kg; height = 190 [4.8] cm) were randomly assigned to 3 training groups performing 2 sets of 4, 6, 8, 6, 8, and 10-minute runs (from first to sixth week, respectively), consisting of 15-second running at Δ%20ASR (MAS + 0.2 × ASR), 95%VIFT, and 120%MAS, with 15 seconds recovery between efforts and a 3-minute relief between sets. Results: All 3 interval interventions significantly (P < .05) enhanced maximum oxygen uptake (), oxygen pulse (), first and second ventilatory threshold (VT1 and VT2), cardiac output (), stroke volume, peak and average power output, testosterone levels, and testosterone-to-cortisol ratio following the training period. Different values of interindividual variability (coefficient of variation) for the percentage changes of the measured variables were observed in response to HIITASR, HIITvIFT, and HIITMAS for (8.7%, 18.8%, 34.6%, respectively), (9.5%, 15.0%, 28.6%), VT1 (9.6%, 19.6%, 34.6%), VT2 (21.8%, 32.4%, 56.7%), (8.2%, 16.9%, 28.8%), stroke volume (7.9%, 15.2%, 23.5%), peak power output (20%, 22%, 37.3%), average power output (21.1%, 21.3%, 32.5%), testosterone (52.9%, 61.6%, 59.9%), and testosterone-to-cortisol ratio (55.1%, 59.5%, 57.8%). Conclusions: Supramaximal HIIT performed at Δ%20ASR resulted in more uniform physiological adaptations than HIIT interventions prescribed using VIFT or MAS. Although hormonal changes do not follow this approach, all the approaches induced an anabolic effect.
The mutual neutralization of hydronium and hydroxide
Authors: Bogot Alon , Poline Mathias , Ji MingChao , Dochain Arnaud , Simonsson Ansgar , Rosén Stefan , Zettergren Henning , Schmidt Henning T. , Thomas Richard D. , Strasser Daniel
Published: January 2024

Mutual neutralization of hydronium (H
3
O
+
) and hydroxide (OH
−
) ions is a very fundamental chemical reaction. Yet, there is only limited experimental evidence about the underlying reaction mechanisms. Here, we report three-dimensional imaging of coincident neutral products of mutual-neutralization reactions at low collision energies of cold and isolated ions in the cryogenic double electrostatic ion-beam storage ring (DESIREE). We identified predominant H
2
O + OH + H and 2OH + H
2
product channels and attributed them to an electron-transfer mechanism, whereas a minor contribution of H
2
O + H
2
O with high internal excitation was attributed to proton transfer. The reported mechanism-resolved internal product excitation, as well as collision-energy and initial ion-temperature dependence, provide a benchmark for modeling charge-transfer mechanisms.
Engineering the thermal stability of a polyphosphate kinase by ancestral sequence reconstruction to expand the temperature boundary for an industrially applicable ATP regeneration system
Authors: Li Zong-Lin , Sun Chuan-Qi , Qing Zhou-Lei , Li Zhi-Min , Liu Hong-Lai
Published: January 2024

ATP-dependent energy-consuming enzymatic reactions are widely used in cell-free biocatalysis. However, the direct addition of large amounts of expensive ATP can greatly increase cost, and enzymatic production is often difficult to achieve as a result. Although a polyphosphate kinase (PPK)-polyphosphate-based ATP regeneration system has the potential to solve this challenge, the generally poor thermal stability of PPKs limits the widespread use of this method. In this paper, we evaluated the thermal stability of a PPK from
Sulfurovum lithotrophicum
(
Sl
PPK2). After directed evolution and computation-supported design, we found that
Sl
PPK2 is very recalcitrant and cannot acquire beneficial mutations. Inspired by the usually outstanding stability of ancestral enzymes, we reconstructed the ancestral sequence of the PPK family and used it as a guide to construct three heat-stable variants of
Sl
PPK2, of which the L35F/T144S variant has a half-life of more than 14 h at 60°C. Molecular dynamics simulations were performed on all enzymes to analyze the reasons for the increased thermal stability. The results showed that mutations at these two positions act synergistically from the interior and surface of the protein, leading to a more compact structure. Finally, the robustness of the L35F/T144S variant was verified in the synthesis of nucleotides at high temperature. In practice, the use of this high-temperature ATP regeneration system can effectively avoid byproduct accumulation. Our work extends the temperature boundary of ATP regeneration and has great potential for industrial applications.

IMPORTANCE

ATP regeneration is an important basic applied study in the field of cell-free biocatalysis. Polyphosphate kinase (PPK) is an enzyme tool widely used for energy regeneration during enzymatic reactions. However, the thermal stability of the PPKs reported to date that can efficiently regenerate ATP is usually poor, which greatly limits their application. In this study, the thermal stability of a difficult-to-engineer PPK from
Sulfurovum lithotrophicum
was improved, guided by an ancestral sequence reconstruction strategy. The optimal variant has a 4.5-fold longer half-life at 60°C than the wild-type enzyme, thus enabling the extension of the temperature boundary for ATP regeneration. The ability of this variant to regenerate ATP was well demonstrated during high-temperature enzymatic production of nucleotides.
On-site filtration of large sample volumes improves the detection of opportunistic pathogens in drinking water distribution systems
Authors: Hozalski Raymond M. , Zhao Xiaotian , Kim Taegyu , LaPara Timothy M.
Published: January 2024

In this study, we compared conventional vacuum filtration of small volumes through disc membranes (effective sample volumes for potable water: 0.3–1.0 L) with filtration of high volumes using ultrafiltration (UF) modules (effective sample volumes for potable water: 10.6–84.5 L) for collecting bacterial biomass from raw, finished, and tap water at seven drinking water systems. Total bacteria,
Legionella
spp.,
Legionella pneumophila
,
Mycobacterium
spp., and
Mycobacterium avium
complex in these samples were enumerated using both conventional quantitative PCR (qPCR) and viability qPCR (using propidium monoazide). In addition, PCR-amplified gene fragments were sequenced for microbial community analysis. The frequency of detection (FOD) of
Legionella
spp. in finished and tap water samples was much greater using UF modules (83% and 77%, respectively) than disc filters (24% and 33%, respectively). The FODs for
Mycobacterium
spp. in raw, finished, and tap water samples were also consistently greater using UF modules than disc filters. Furthermore, the number of observed operational taxonomic units and diversity index values for finished and tap water samples were often substantially greater when using UF modules as compared to disc filters. Conventional and viability qPCR yielded similar results, suggesting that membrane-compromised cells represented a minor fraction of total bacterial biomass. In conclusion, our research demonstrates that large-volume filtration using UF modules improved the detection of opportunistic pathogens at the low concentrations typically found in public drinking water systems and that the majority of bacteria in these systems appear to be viable in spite of disinfection with free chlorine and/or chloramine.

IMPORTANCE

Opportunistic pathogens, such as
Legionella pneumophila
, are a growing public health concern. In this study, we compared sample collection and enumeration methods on raw, finished, and tap water at seven water systems throughout the State of Minnesota, USA. The results showed that on-site filtration of large water volumes (i.e., 500–1,000 L) using ultrafiltration membrane modules improved the frequency of detection of relatively rare organisms, including opportunistic pathogens, compared to the common approach of filtering about 1 L using disc membranes. Furthermore, results from viability quantitative PCR (qPCR) with propidium monoazide were similar to conventional qPCR, suggesting that membrane-compromised cells represent an insignificant fraction of microorganisms. Results from these ultrafiltration membrane modules should lead to a better understanding of the microbial ecology of drinking water distribution systems and their potential to inoculate premise plumbing systems with opportunistic pathogens where conditions are more favorable for their growth.
An RNA replicon system to investigate promising inhibitors of feline coronavirus
Authors: Schmied Kimberly , Ehmann Rosina , Kristen-Burmann Claudia , Ebert Nadine , Barut Güliz Tuba , Almeida Lea , Kelly Jenna N. , Thomann Lisa , Stalder Hanspeter , Lang Reto , Tekes Gergely , Thiel Volker
Published: January 2024

FIPV is of great significance in the cat population around the world, causing 0.3%–1.4% of feline deaths in veterinary practices (2). As there are neither effective preventive measures nor approved treatment options available, there is an urgent need to identify antiviral drugs against FIPV. Our FCoV replicon system provides a valuable tool for drug discovery
in vitro
. Due to the lack of cell culture systems for serotype I FCoVs (the serotype most prevalent in the feline population) (2), a different system is needed to study these viruses. A viral replicon system is a valuable tool for studying FCoVs. Overall, our results demonstrate the utility of the serotype I feline coronavirus replicon system for antiviral screening as well as to study this virus in general. We propose several compounds representing promising candidates for future clinical trials and ultimately with the potential to save cats suffering from FIP.
Bacteriophage P22 SieA-mediated superinfection exclusion
Authors: Leavitt Justin C. , Woodbury Brianna M. , Gilcrease Eddie B. , Bridges Charles M. , Teschke Carolyn M. , Casjens Sherwood R.
Published: January 2024

The ongoing evolutionary battle between bacteria and the viruses that infect them is a critical feature of bacterial ecology on Earth. Viruses can kill bacteria by infecting them. However, when their chromosomes are integrated into a bacterial genome as a prophage, viruses can also protect the host bacterium by expressing genes whose products defend against infection by other viruses. This defense property is called “superinfection exclusion.” A significant fraction of bacteria harbor prophages that encode such protective systems, and there are many different molecular strategies by which superinfection exclusion is mediated. This report is the first to describe the mechanism by which bacteriophage P22 SieA superinfection exclusion protein protects its host bacterium from infection by other P22-like phages. The P22 prophage-encoded inner membrane SieA protein prevents infection by blocking transport of superinfecting phage DNA across the inner membrane during injection.
Bacteriophage tRNA-dependent lysogeny: requirement of phage-encoded tRNA genes for establishment of lysogeny
Authors: Guerrero-Bustamante Carlos A. , Hatfull Graham F.
Published: January 2024

Bacteriophages are the most numerous biological entities in the biosphere, and a substantial proportion of phages are temperate, forming stable lysogens in which a prophage copy of the genome integrates into the bacterial chromosome. Many phages encode a variety of tRNA genes whose roles are poorly understood, although it has been proposed that they enhance translational efficiencies in lytic growth or that they counteract host defenses that degrade host tRNAs. Here, we show that phage-encoded tRNAs play key roles in the establishment of lysogeny of some temperate phages. They do so by compensating for the loss of tRNA function when phages integrate at an
attB
site overlapping a tRNA gene but fail to reconstruct the tRNA at the attachment junction. In this system of tRNA-dependent lysogeny, the phage-encoded tRNA is required for lysogeny, and deletion of the phage tRNA gives rise to a clear plaque phenotype and obligate lytic growth.
Successive accretions of future allochthonous terranes and multiple subduction zone jumps: Implications for Tethyan evolution
Authors: Yan Zhiyong , Chen Lin , Zuza Andrew V. , Meng Qingren
Published: January 2024

The accretion of future allochthonous terranes (e.g., microcontinents or oceanic plateaus) onto the southern margin of Asia occurred repeatedly during the evolution and closure of the Tethyan oceanic realm, but the specific geodynamic processes of this protracted convergence, successive accretion, and subduction zone initiation remain largely unknown. Here, we use numerical models to better understand the dynamics that govern multiple terrane accretions and the polarity of new subduction zone initiation. Our results show that the sediments surrounding the future terranes and the structural complexity of the overriding plate are important factors that affect accretion of multiple plates and guide subduction polarity. Wide (≥400 km) and buoyant terranes with sediments behind them and fast continental plate motions are favorable for multiple unidirectional subduction zone jumps, which are also referred to as subduction zone transference, and successive terrane-accretion events. The jumping times (~3–20 + m.y.) are mainly determined by the convergence rates and rheology of the overriding complex plate with preceding terrane collisions, which increase with slower convergence rates and/or a greater number of preceding terrane collisions. Our work provides new insights into the key geodynamic conditions governing multiple subduction zone jumps induced by successive accretion and discusses Tethyan evolution at a macro level. More than 50 m.y. after India-Asia collision, subduction has yet to initiate along the southern Indian plate, which may be the joint result of slower plate convergence and partitioned deformation across southern Asia.
Increase in magma supply to Sakurajima volcano’s (Japan) shallow magma chamber over the past 500 years
Authors: Huber Christian , Toramaru Atsushi
Published: January 2024

Constraining the magma supply to a subvolcanic reservoir is crucial to characterizing unrest and evaluating the potential for a forthcoming eruption. With the advent of GPS, tiltmeters, and satellite interferometry, it has been possible to infer changes in the supply rate of magma to shallow reservoirs over time scales of as much as decades. While these methods have impacted our ability to characterize volcanic unrest, they only probe magmatic activity over short time scales. Here, we constrain changes in magma supply rate at Sakurajima volcano (Kyushu, Japan) over the past five centuries. The combination of thermo-mechanical modeling, documented eruption history, and textural analyses of pumices allows us to tightly constrain the long-term rate of magma supply to the subvolcanic chamber through time. Specifically, we find that magma supply rate has increased by roughly an order of magnitude over the past 500 years and that the bubble content in the magma chamber has increased over time, explaining the changes in eruption volume between the Bunmei (ca. A.D. 1470), An-ei (ca. A.D. 1780), and Taisho (A.D. 1914) eruptions.
Does insulin pump therapy offer benefits for behaviour, mood, cognition and HbA1c in children and adolescents with type 1 diabetes? A randomised controlled trial with observational follow-up
Authors: O'Connell Michele A , Northam Elisabeth A , Brown Amy , Papoutsis Jennifer , Schuster Tibor , Skinner Timothy , Jenkins Alicia J , Ambler Geoffrey R , Cameron Fergus J
Published: January 2024

Aims

Improved behaviour, mood, cognition and HbA1c have been reported with short-term use of continuous subcutaneous insulin infusion (CSII) in youth with type 1 diabetes (T1D). We sought to re-examine these findings in a randomised controlled trial (RCT), with longitudinal follow-up.

Methods

RCT of youth aged 7–15 years with T1D, at two tertiary paediatric centres. Participants were randomised to commence CSII or continue multiple daily injections (MDI). Behaviour, mood, cognition and HbA1c were assessed. Primary outcome was difference in parent-reported behaviour (BASC-2) at 4 months. After the 4-month RCT, MDI participants commenced CSII; outcomes were reassessed at +2 years.

Results

Participating youth (n=101) were randomised to CSII (n=56) or MDI (n=45). Significant differences favouring CSII were found at 4 months in parent-reported behaviour problems (Cohen’s d 0.41 (95% CI 0.004 to 0.795); p=0.048) and HbA1c (mean (95% CI) difference: 7 (2.3 to 11.7) mmol/mol (0.6% (0.2 to 1.0%); p=0.001)). Improvements from baseline were documented in mood and cognitive outcomes in both study groups over the 4-month RCT; however, no between-group differences were evident at 4 months. Sixteen of 76 (21%) participants completing assessments at +2 years had discontinued CSII. In n=60 still using CSII, measurements of behaviour, mood and HbA1c were comparable to baseline.

Conclusions

Parent-reported behaviour problems and HbA1c, but not mood or neurocognitive outcomes, were clinically significantly lower with CSII, relative to MDI, after 4 months. Observational follow-up indicated no impact of treatment modality at +2 years, relative to baseline levels. Taken together, these data indicate that use of CSII alone does not comprehensively benefit neuropsychological outcomes in childhood T1D.
Pattern and prognostic factors for kidney function progression in survivors of children with acute kidney injury: a cohort study
Authors: Hui Wun Fung , Chan Vivian Pui Ying , Cheung Wing Lum , Ku Shu Wing , Hon Kam Lun
Published: January 2024

Objective

To examine the pattern of kidney function progression after acute kidney injury (AKI) and identify the associated risk factors.

Design

A prospective cohort study was conducted from June 2020 to June 2021 on children aged 1 month to <18 years admitted to the paediatric intensive care unit (PICU). Acute kidney disease (AKD) was defined as AKI persisting from 7 to 90 days after diagnosis. The natural history and prognostic factors of kidney function progression were determined.

Results

Among the 253 admissions with a median (IQR) age of 4.9 (9.7) years, the AKI and AKD incidence was 41.9% and 52.2% respectively. The incidence of estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2was 6.7% at 90 days and 11.9% at latest follow-up. Severe and prolonged AKI and higher degree of nephrotoxic medication exposure were associated with AKD development. The severity and duration of AKI and AKD significantly predicted kidney function non-recovery. Children with both entities exhibited a higher peak-to-baseline serum creatinine level ratio at 90 days (1.6 vs 1.0, p<0.001), and a more pronounced decline in eGFR (21% vs 19%, p=0.028) during the follow-up period compared with those without AKI/AKD. They also had an increased risk of having eGFR <90 mL/min/1.73 m2at 90 days (HR 14.9 (95% CI 1.8 to 124.0)) and latest follow-up (HR 3.8 (95% CI 1.1 to 13.1)).

Conclusions

AKI and AKD are prevalent among critically ill children and pose substantial risk for non-recovery of kidney function among PICU survivors. A structural follow-up visit for AKI survivors to monitor kidney function progression is advocated.
Neuroimaging changes in the pregeniculate visual pathway and chiasmal enlargement in Leber hereditary optic neuropathy
Authors: Xu Xintong , Zhou Huanfen , Sun Mingming , Li Yuyu , Chen Biyue , Chen Xiyun , Xu Quangang , Yu-Wai-Man Patrick , Wei Shihui
Published: January 2024

Purpose

To describe the pattern of MRI changes in the pregeniculate visual pathway in Leber hereditary optic neuropathy (LHON).

Method

This retrospective observational study enrolled 60 patients with LHON between January 2015 and December 2021. The abnormal MRI features seen in the pregeniculate visual pathway were investigated, and then correlated with the causative mitochondrial DNA (mtDNA) mutation, the distribution of the MRI lesions and the duration of vision loss.

Result

The cohort included 48 (80%) males and 53 (88%) had bilateral vision loss. The median age of onset was 17.0 years (range 4.0–58.0). 28 (47%) patients had the m.11778G>A mutation. 34 (57%) patients had T2 hyperintensity (HS) in the pregeniculate visual pathway and 13 (22%) patients with chiasmal enlargement. 20 patients (71%) carrying the m.11778G>A mutation had T2 HS, significantly more than the 14 patients (44%) with T2 HS in the other LHON mutation groups (p=0.039). Furthermore, significantly more patients in the m.11778G>A group (16 patients (57%)) had T2 HS in optic chiasm (OCh)/optic tract (OTr) than the other LHON mutation groups (7 patients (22%), p=0.005). Optic chiasmal enlargement was more common in patients with vision loss duration <3 months compared with those ≥3 months (p=0.028).

Conclusion

T2 HS in the pregeniculate visual pathway is a frequent finding in LHON. Signal changes in the OCh/OTr and chiasmal enlargement, in particular within the first 3 months of visual loss, were more commonly seen in patients carrying the m.11778G>A mtDNA mutation, which may be of diagnostic significance.
Sri Lanka’s COVID-19 response and maintaining health services: implications for future pandemics
Authors: Rannan-Eliya Ravindra Prasan , Ghaffoor Azrah , Amarasinghe Sarasi , Nirmani Manage Dhanusha , Wijemunige Nilmini , Perera Sanjay , Samarage Sarath , Dalpatadu KCS , Wisidagama Niroshani , Fonseka Sachini , Kumara Nalin , Selvaratnam Ahthiga , Dananjana Thimani
Published: January 2024

This study examines how Sri Lanka, a lower-middle income country, managed its COVID-19 response and maintained health services. It draws on an extensive document review, key informant interviews and a national survey of public experience and opinion to assess what Sri Lanka did, its effectiveness and why.

Owing to a strong health system and luck, Sri Lanka stopped the first wave of COVID-19 infections, and it adopted a ‘Zero-COVID’ approach with the explicit goal of stopping outbreaks. This was initially effective. Outbreaks reduced healthcare use, but with minimal impact on health outcomes. But from end-2020, Sri Lanka switched its approach to tolerating transmission and mitigation. It took proactive actions to maintain healthcare access, and it pursued a COVID-19 vaccination effort that was successful in covering its adult population rapidly and with minimal disparities. Despite this, widespread transmission during 2021–2022 disrupted health services through the pressure on health facilities of patients with COVID-19 and infection of healthcare workers, and because COVID-19 anxiety discouraged patients from seeking healthcare. This led to substantial mortality and more than 30 000 excess deaths by 2022.

We find that Sri Lanka abandoned its initially successful approach, because it failed to understand that its chosen strategy required symptomatic PCR testing in primary care. Failure to invest in testing was compounded by groupthink and a medical culture averse to testing.

Sri Lanka’s experience confirms that strong public health capacities, robust healthcare systems and intersectoral action are critical for pandemic response. It shows that civilian–military collaboration can be beneficial but contested, and that lack of fiscal space will undermine any response. It also demonstrates that pandemic preparedness cannot guarantee a successful pandemic response. Policy and research must pay more attention to improving decision-making processes when faced with pandemics involving novel pathogens, rapid spread, and substantial scientific uncertainty.
Levodopa use in Australia: an analysis of Pharmaceutical Benefits Scheme 10% data
Authors: Evans Andrew , Waterhouse Benjamin J
Published: January 2024

Background

Levodopa remains the mainstay of treatment of Parkinson’s disease, however, over time motor fluctuations and levodopa-induced dyskinesia develop, requiring add-on therapies to control emerging symptoms. To date, however, there is no clear consensus in Australia, or elsewhere, at which dose of levodopa that add-on therapies should be considered.

Objectives

The purpose of this study was to examine the treatment patterns of patients with Parkinson’s disease in Australia, with particular focus on levodopa doses at the time of first add-on.

Methods

This was a retrospective, observational, non-interventional study of patients with Parkinson’s disease within the Australian Department of Human Services Pharmaceutical Benefits Scheme (PBS) 10% sample. Data on all reimbursed prescriptions (both general and concession), prescriber type and item code were extracted for patients who were dispensed at least three PBS reimbursed prescriptions for levodopa in the previous 12 months prescription from 1 January 2007 to 31 December 2021.

Results

154 850 unique patients were included, of whom 42 330 (27%) commenced add-on therapy during the period. In the 12 months prior to add-on therapy, levodopa doses ranged from 100 mg/day to 1000 mg/day. The majority of patients were prescribed add-on therapy by a neurologist and approximately 40% of patients were prescribed levodopa doses of 600 mg/day or more prior to the first add-on therapy being initiated.

Conclusions

A large proportion of patients in Australia are managed with levodopa monotherapy doses that are considered high and many of these patients may benefit from the addition of add-on therapy to their regimen.
Sudden unilateral audiovestibular loss due to acute labyrinthine haemorrhage can be missed on early MRI brain sequences: case report
Authors: Harrison Patrick , Blazak John , Richmond Joshua , Fraser-Kirk Kristy , Hoffmann Aliese , Collins Grant , Tsang Benjamin K-T
Published: January 2024

Background

Labyrinthine haemorrhage is a rare vascular disorder often presenting with the triad of acute vertigo, sudden sensorineural hearing loss and tinnitus. There are minimal reports on imaging progression over the acute period.

Index case

A woman in her mid-40s presented with acute vertigo, sudden left-sided hearing loss and tinnitus, consistent with acute unilateral audiovestibular loss. Left peripheral vestibular hypofunction was confirmed acutely on video head impulse testing, and pure tone audiometry showed a profound left sensorineural hearing loss. An MRI brain including diffusion-weighted imaging within 24 hours was normal. Delayed MRI brain and internal acoustic canal after 7 days demonstrated increased 3D fluid-attenuated inversion recovery and T1 signal throughout the left cochlea and semicircular canals, without contrast enhancement. This was consistent with labyrinthine haemorrhage. She received early oral prednisone followed by three doses of intratympanic dexamethasone. At 12 months follow-up the patient remained profoundly deaf, however, balance and vestibular symptoms improved with early vestibular physical rehabilitation.

Conclusion

We report a case of acute labyrinthine haemorrhage missed on an early MRI brain sequence. This diagnosis should be considered in presentations of acute audiovestibular loss, and delayed MRI including internal auditory canal sequences may be important for diagnosis.
Artificial intelligence across oncology specialties: current applications and emerging tools
Authors: Kang John , Lafata Kyle , Kim Ellen , Yao Christopher , Lin Frank , Rattay Tim , Nori Harsha , Katsoulakis Evangelia , Lee Christoph Ilsuk
Published: January 2024

Oncology is becoming increasingly personalised through advancements in precision in diagnostics and therapeutics, with more and more data available on both ends to create individualised plans. The depth and breadth of data are outpacing our natural ability to interpret it. Artificial intelligence (AI) provides a solution to ingest and digest this data deluge to improve detection, prediction and skill development. In this review, we provide multidisciplinary perspectives on oncology applications touched by AI—imaging, pathology, patient triage, radiotherapy, genomics-driven therapy and surgery—and integration with existing tools—natural language processing, digital twins and clinical informatics.
Randomised placebo-controlled trial of antenatal corticosteroids for planned birth in twins (STOPPIT-3): study protocol
Authors: Murray Sarah , Thompson Jessica , Townsend Rosie C , Deidda Manuela , Boyd Kathleen Anne , Norman Jane E , Norrie John , Boardman James P , Luyt Karen , Khalil Asma , Bick Debra , Reed Keith , Denton Jane , Fenwick Natasha , Keerie Catriona , Reynolds Rebecca , Stock Sarah Jane
Published: January 2024

Introduction

The aim of the STOPPIT-3 study is to determine the clinical and cost effectiveness of antenatal corticosteroids (ACS) prior to planned birth of twins in a multicentre placebo-controlled trial with internal pilot.

Methods and analysis

This study will comprise a multicentre, double-blinded, randomised, placebo-controlled trial in at least 50 UK obstetric units. The target population is 1552 women with a twin pregnancy and a planned birth between 35 and 38+6 weeks’ gestation recruited from antenatal clinics. Women will be randomised to Dexamethasone Phosphate (24 mg) or saline administered via two intramuscular injections 24 hours apart, 24–120 hours prior to scheduled birth.

Outcomes

The primary outcome is need for respiratory support within 72 hours of birth. Secondary and safety outcomes will be included. Cognitive and language development at age 2 years will be assessed in a subset of participants using the Parent report of Children’s Abilities-Revised questionnaire. We will also determine the cost effectiveness of the treatment with ACS compared with placebo.

Ethics and dissemination

STOPPIT-3 has been funded and approved by the National Institute of Healthcare Research. It has been approved by the West Midlands Research Ethics Committee (22/WM/0018). The results will be disseminated via publication in peer-reviewed journals and conference presentation and will also be communicated to the public via links with charity partners and social media.

Trial sponsor

The University of Edinburgh and Lothian Health Board ACCORD, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ.

Trial registration number

ISRCTN59959611.
Equity of health resource allocation in Chongqing, China, in 2021: a cross-sectional study
Authors: Wei Hao , Jiang Ke , Zhao Yong , Pu Chuan
Published: January 2024

Background

Chongqing, the most populous city in Southwest China. This study aims to examine the equity of health resource allocation in Chongqing using the latest statistics, analyse possible shortcomings and propose strategies to address these issues.

Methods

This cross-sectional study used healthcare resource, population, area and gross domestic product data from the Seventh National Census Bulletin of Chongqing, the National County Statistical Yearbook, the Chongqing Municipal Bureau of Statistics and the Chongqing Health Statistical Yearbook 2022. We also studied the equity of health resource allocation in Chongqing by using the Gini coefficient, Lorenz curve and Theil index, and used the Analytical Hierarchy Process and Technique for Order of Preference by Similarity to Ideal Solution (AHP–TOPSIS) method to comprehensively evaluate the health resources in the four major regions of Chongqing.

Results

The Gini coefficient of health resources in Chongqing in 2021 was the highest when allocated according to geographical area, between 0.4285 and 0.6081, both of which exceeded 0.4, and the Gini coefficient of medical equipment was the highest and exceeded 0.6. The inter-regional Theil index of each resource was greater than the intraregional Theil index, and the contribution of inter-regional differences ranged from 64.83% to 80.21%. The results of the AHP–TOPSIS method showed that the relative proximity between health resources and ideal solutions in four regions of Chongqing ranged from 0.0753 to 0.9277.

Conclusion

The allocation of health resources in Chongqing exhibits pronounced inequities, particularly in the distribution of medical equipment according to geographical area. Moreover, there exists a substantial gap in the equity of health resource allocation among the four regions of Chongqing. As such, this study emphasises the need for Chongqing, China, to prioritise the equitable allocation of health resources and increase consideration of geographic factors. Implementing measures to promote equitable allocation of health resources, particularly in geographic terms, is critical.
Cross-sectional study investigating the relationship between pit recovery time and serum albumin levels in bilateral lower extremity pitting oedema
Authors: Ono Ryosuke , Horibata Ken
Published: January 2024

Objectives

In this study, we re-evaluated the relationship between pit recovery time (PRT) and serum albumin levels and elucidated the factors influencing PRT.

Design

Cross-sectional study.

Setting

Patients who visited the outpatient department or were admitted to a small urban hospital in Japan.

Participants

135 adult Japanese patients with bilateral lower extremity pitting oedema.

Interventions

Primary and secondary outcome measures: this study assessed the correlation between PRT and serum albumin levels, calculated the predictive accuracy for identifying a group with low albumin levels when the PRT of the lower leg was <40 s, and identified variables that influence PRT.

Results

We found no significant correlation between lower leg PRT and serum albumin levels. Furthermore, a PRT of <40 s was largely ineffective in predicting low albumin levels. Factors influencing PRT included the diagnosis of malnutrition oedema, examinations conducted during hospitalisation, diagnosis of cardiac oedema, use of diuretics, thickness of the lower limb soft tissue, serum creatinine level, estimated right ventricular systolic pressure (RVSP), age, serum albumin level, potassium level and blood urea nitrogen to serum creatinine ratio. Notable correlations with PRT were observed in relation to lower limb soft tissue thickness, age and estimated RVSP.

Conclusions

Given that the PRT is influenced by multiple factors, its correlation with serum albumin levels is weak. Thus, predicting hypoalbuminaemia based solely on PRT is inaccurate.
Evaluation of the willingness to perform cardiopulmonary resuscitation (CPR) with automated external defibrillator (AED) among Hong Kong Chinese using the theory of planned behaviour framework: an online cross-sectional survey
Authors: Tam Victor C W , Kwok Anthony Wai Leung
Published: January 2024

Introduction

Bystander cardiopulmonary resuscitation (CPR) and defibrillation by an automated external defibrillator (AED) in out-of-hospital cardiac arrest (OHCA) events were low in Hong Kong (HK). This study evaluated the willingness and associated factors of performing CPR with AED in HK using the theory of planned behaviour (TPB).

Methods

A total of 1449 responses from HK Chinese aged 15–64 years were collected in a cross-sectional online survey using convenience sampling on social media including Facebook, Instagram and WhatsApp. Three TPB determinants, namely attitude, subjective norm and perceived behavioural control; and perceived barriers were asked using 5-point Likert scales. Associations between each predictor and willingness to perform CPR with AED were evaluated using univariate ordinal regressions. Predictive models were constructed using hierarchical multiple ordinal regressions (MOR) to explore associated predictors and the adjusted OR (ORadj).

Results

There were 44.8% and 47.8% of respondents who were willing to perform CPR and use AED, respectively. Young adults aged 18–25 years demonstrated the lowest willingness to perform CPR (ORadj=0.63, 95% CI 0.42 to 0.94, p=0.023). Knowledge level was not associated with either CPR or AED willingness, thus was eliminated in backward selection in the MOR. Attitude, subjective norm and perceived behavioural control were all positively associated with both willingness (all ORadj>1.5, p<0.001), while perceived barriers were associated with CPR willingness only (ORadj=0.77, 95% CI 0.66 to 0.91, p=0.002).

Conclusions

Utilisation of the TPB framework in CPR and AED community education would fill the ‘know-do’ gap and enhance the community’s willingness to perform CPR and use an AED.
Pathogenesis and precision medicine for predicting response in inflammatory bowel disease: advances and future directions
Authors: Little Robert D , Jayawardana Thisun , Koentgen Sabrina , Zhang Fan , Connor Susan J , Boussioutas Alex , Ward Mark G , Gibson Peter R , Sparrow Miles P , Hold Georgina L
Published: January 2024

The pathogenesis of inflammatory bowel disease (IBD) is complex and multifactorial. Undertreated disease has substantial individual and societal consequences. Current patient classification and subsequent positioning of IBD therapy are based on crude, readily accessible clinical data. These broad parameters are unlikely to reflect underlying molecular profiles and may account for the observed heterogeneity in treatment response. Precision medicine offers identification and integration of molecular profiles into clinical decision-making. Despite several promising scientific and technological advances, the pathogenesis and targetable molecular drivers of IBD remain incompletely understood. Precision medicine therefore remains aspirational. This comprehensive narrative review describes our current understanding of IBD pathophysiology, highlights preliminary genetic, immunological and microbial predictors of treatment response and outlines the role of ‘big data’ and machine learning in the path towards precision medicine.
Can acutely ill patients predict their outcomes? A scoping review
Authors: Mols Elisabeth Margaretha , Haak Harm , Holland Mark , Schouten Bo , Ibsen Stine , Merten Hanneke , Christensen Erika Frischknecht , Nanayakkara Prabath W B , Nickel Christian Hans , Weichert Immo , Kellett John , Subbe Christian Peter , Kremers Marjolein N T
Published: January 2024

Introduction

The full impact of an acute illness on subsequent health is seldom explicitly discussed with patients. Patients’ estimates of their likely prognosis have been explored in chronic care settings and can contribute to the improvement of clinical outcomes and patient satisfaction. This scoping review aimed to identify studies of acutely ill patients’ estimates of their outcomes and potential benefits for their care.

Methods

A search was conducted in PubMed, Embase, Web of Science and Google Scholar, using terms related to prognostication and acute care. After removal of duplicates, all articles were assessed for relevance by six investigator pairs; disagreements were resolved by a third investigator. Risk of bias was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions.

Results

Our search identified 3265 articles, of which 10 were included. The methods of assessing self-prognostication were very heterogeneous. Patients seem to be able to predict their need for hospital admission in certain settings, but not their length of stay. The severity of their symptoms and the burden of their disease are often overestimated or underestimated by patients. Patients with severe health conditions and their relatives tend to be overoptimistic about the likely outcome.

Conclusion

The understanding of acutely ill patients of their likely outcomes and benefits of treatment has not been adequately studied and is a major knowledge gap. Limited published literature suggests patients may be able to predict their need for hospital admission. Illness perception may influence help-seeking behaviour, speed of recovery and subsequent quality of life. Knowledge of patients’ self-prognosis may enhance communication between patients and their physicians, which improves patient-centred care.
Adults’ exposure to adverse childhood experiences in the United States nationwide and in each state: modeled estimates from 2019-2020
Authors: Aslam Maria V , Peterson Cora , Swedo Elizabeth , Niolon Phyllis H , Bacon Sarah , Florence Curtis
Published: January 2024

Background

Although preventable, adverse childhood experiences (ACEs) can result in lifelong health harms. Current surveillance data on adults’ exposure to ACEs are either unavailable or incomplete for many U.S. states.

Methods

Current estimates of the proportion of U.S. adults with past ACEs exposures were obtained by analysing individual-level data from 2019 to 2020 Behavioural Risk Factor Surveillance System―annual nationally representative survey of noninstitutionalized adults aged 18+years. Standardised questions measuring ACEs exposures (presence of household member with mental illness, substance abuse, or incarceration; parental separation; witnessing intimate partner violence; experiencing physical, emotional, or sexual abuse during childhood) were categorised into 0, 1, 2–3, or 4+ACEs and reported by sociodemographic group in each state. Missing ACEs responses (state did not offer ACEs questions or offered to only some respondents; respondent skipped questions) were modelled through multilevel mixed-effects logistic (MMEL) and jackknifed MMEL regressions.

Results

In 2019–2020, an estimated 62.8% of U.S. adults had past exposure to 1+ACEs (range: 54.9% in Connecticut; 72.5% in Maine), including 22.4% of adults who were exposed to 4+ACEs (range: 11.9% in Connecticut; 32.8% in Nevada). At the national and state levels, exposure to 4+ACEs was highest among adults aged 18–34 years, those who did not graduate from high school, or adults who did not have a healthcare provider. Racial/ethnic distribution of adults exposed to 4+ACEs varied by age and state.

Conclusions

ACEs are common but not equally distributed. ACEs exposures estimated by state and sociodemographic group can help decisionmakers focus public health interventions on populations disproportionately impacted in their area.