bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors for invasive home mechanical ventilation duration in bronchopulmonary dysplasia
Authors: Foster Carolyn , Noreen Paige , Grage Jennifer , Kwon Soyang , Hird‐McCorry Lindsey P. , Janus Angela , Davis Matthew M. , Goodman Denise , Laguna Theresa
Published: April 2023

Background

Children with bronchopulmonary dysplasia (BPD) who require invasive home mechanical ventilation (IHMV) are medically vulnerable and experience high caregiving and healthcare costs. Predictors for duration of IHMV in children with BPD remain unclear, which can make prognostication and decision‐making challenging.

Methods

A retrospective cohort study of children with BPD requiring IHMV was conducted from independent children's hospital records (2005–2021). The primary outcome was IHMV duration, defined as time from initial discharge home on IHMV until cessation of positive pressure ventilation (day and night). Two new variables were included: discharge age corrected for tracheostomy (DACT) (chronological age at discharge minus age at tracheostomy) and level of ventilator support at discharge (minute ventilation per kg per day). Univariable Cox regression was performed with variables of interest compared to IHMV duration. Significant nonlinear factors (p < 0.05) were included in the multivariable analysis.

Results

One‐hundred‐and‐nineteen patients used IHMV primarily for BPD. Patient median index hospitalization lasted 12 months (interquartile range [IQR] 8.0,14.4). Once home, half of the patients were weaned off IHMV by 36.0 months and 90% by 52.2 months. Being Hispanic/Latinx ethnicity (hazard ratio [HR] 0.14 (95% confidence interval [CI] 0.04, 0.53), p < 0.01) and having a higher DACT were associated with increased IHMV duration (HR 0.66 (CI 0.43, 0.98), p < 0.05).

Conclusions

Disparity in IHMV duration exists among patients using IHMV after prematurity. Prospective multisite studies that further investigate new analytic variables, such as DACT and level of ventilator support, and address standardization of IHMV care are needed to create more equitable IHMV management strategies.
Towards a comprehensive framework to analyse the benefits of openness for sustainability‐oriented innovation: A systematic literature review
Authors: Miranda Luis Francisco , Cruz‐Cázares Claudio , Saunila Minna
Published: April 2023

This study systematically reviews the scientific literature on the role of open innovation in addressing current and emerging societal and environmental challenges. To do so, we analysed the what, how, who and why of integrating external partners for sustainability purposes. We found a clear predominance of open innovation mechanisms to develop environmental innovations rather than innovations focused on a triple bottom line. We identified at least four mechanisms associated with the inbound mode of open innovation (crowdsourcing, lead‐user workshops, intermediation, and experiments and discussion sessions) and 10 mechanisms related to the coupled mode of open innovation (alliance, business‐non‐profit engagement, co‐creation, joint ventures, cooperation, collaborative innovation contests, coopetition, cross‐sector partnerships, joint development projects, and innovation networks). Even though sustainability‐oriented innovation promises to be a source of societal transformation and entrepreneurial opportunities, we found that firms can face some tensions when simultaneously addressing financial, environmental and social purposes.
Tendency Regulation of Competing Reactions Toward Highly Reversible Tin Anode for Aqueous Alkaline Batteries
Authors: Xu Diyu , Xie Jinhao , Zhou Lijun , Yang Fan , Wang Yi , Yang Zujin , Wang Fuxin , Zhang Haozhe , Lu Xihong
Published: April 2023

Investigating dendrite‐free stripping/plating anodes is highly significant for advancing the practical application of aqueous alkaline batteries. Sn has been identified as a promising candidate for anode material, but its deposition/dissolution efficiency is hindered by the strong electrostatic repulsion between Sn(OH)3− and the substrate. Herein, this work constructs a nondense copper layer which serves as stannophile and hydrogen evolution inhibitor to adjust the tendency of competing reactions on Sn foil surface, thus achieving a highly reversible Sn anode. The interactions between the deposited Sn and the substrates are also strengthened to prevent shedding. Notably, the ratio of Sn redox reaction is significantly boosted from ≈20% to ≈100%, which results in outstanding cycling stability over 560 h at 10 mA cm−2. A Sn//Ni(OH)2 battery device is also demonstrated with capacities from 0.94 to 22.4 mA h cm−2 and maximum stability of 1800 cycles.
Harnessing Nucleic Acids Nanotechnology for Bone/Cartilage Regeneration
Authors: Han Yafei , Cao Liehu , Li Guangfeng , Zhou Fengjin , Bai Long , Su Jiacan
Published: April 2023

The effective regeneration of weight‐bearing bone defects and critical‐sized cartilage defects remains a significant clinical challenge. Traditional treatments such as autologous and allograft bone grafting have not been successful in achieving the desired outcomes, necessitating the need for innovative therapeutic approaches. Nucleic acids have attracted significant attention due to their ability to be designed to form discrete structures and programmed to perform specific functions at the nanoscale. The advantages of nucleic acid nanotechnology offer numerous opportunities for in‐cell and in vivo applications, and hold great promise for advancing the field of biomaterials. In this review, the current abilities of nucleic acid nanotechnology to be applied in bone and cartilage regeneration are summarized and insights into the challenges and future directions for the development of this technology are provided.
Signal Transduction in Artificial Cells
Authors: Yu Xiaolei , Mukwaya Vincent , Mann Stephen , Dou Hongjing
Published: April 2023

In recent years, significant progress has been made in the emerging field of constructing biomimetic soft compartments with life‐like behaviors. Given that biological activities occur under a flux of energy and matter exchange, the implementation of rudimentary signaling pathways in artificial cells (protocells) is a prerequisite for the development of adaptive sense‐response phenotypes in cytomimetic models. Herein, recent approaches to the integration of signal transduction modules in model protocells prepared by bottom‐up construction are discussed. The approaches are classified into two categories involving invasive biochemical signals or non‐invasive physical stimuli. In the former mechanism, transducers with intrinsic recognition capability respond with high specificity, while in the latter, artificial cells respond through intra‐protocellular energy transduction. Although major challenges remain in the pursuit of a sophisticated artificial signaling network for the orchestration of higher‐order cytomimetic models, significant advances have been made in establishing rudimentary protocell communication networks, providing novel organizational models for the development of life‐like microsystems and new avenues in protoliving technologies.
Model-Based Controlling Approaches for Manufacturing Processes
Authors: Rüppel Adrian Karl , Ay Muzaffer , Biernat Benedikt , Kunze Ike , Landwehr Markus , Mann Samuel , Pennekamp Jan , Rabe Pascal , Sanders Mark P. , Scheurenberg Dominik , Schiller Sven , Xi Tiandong , Abel Dirk , Bergs Thomas , Brecher Christian , Reisgen Uwe , Schmitt Robert H. , Wehrle Klaus
Published: April 2023

The main objectives in production technology are quality assurance, cost reduction, and guaranteed process safety and stability. Digital shadows enable a more comprehensive understanding and monitoring of processes on shop floor level. Thus, process information becomes available between decision levels, and the aforementioned criteria regarding quality, cost, or safety can be included in control decisions for production processes. The contextual data for digital shadows typically arises from heterogeneous sources. At shop floor level, the proximity to the process requires usage of available data as well as domain knowledge. Data sources need to be selected, synchronized, and processed. Especially high-frequency data requires algorithms for intelligent distribution and efficient filtering of the main information using real-time devices and in-network computing. Real-time data is enriched by simulations, metadata from product planning, and information across the whole process chain. Well-established analytical and empirical models serve as the base for new hybrid, gray box approaches. These models are then applied to optimize production process control by maximizing the productivity under given quality and safety constraints. To store and reuse the developed models, ontologies are developed and a data lake infrastructure is utilized and constantly enlarged laying the basis for a World Wide Lab (WWL). Finally, closing the control loop requires efficient quality assessment, immediately after the process and directly on the machine. This chapter addresses works in a connected job shop to acquire data, identify and optimize models, and automate systems and their deployment in the Internet of Production (IoP).
Science and Values:
Authors: Douglas Heather
Published: April 2023

Since the mid-twentieth century, insulating science from social and ethical values has been something of an obsession for philosophers of science. Philosophers articulated, and then staunchly defended, a value-free ideal for science. Philosophers were willing to concede the “context of discovery” to the influence of values, but argued that the “context of justification” had no place for social values. This view was supported by three ideas: (1) that societal values can add no confirmatory weight to empirical claims; (2) that values distinctive to scientific theory choice could guide scientists when faced with inferential decisions; and (3) that the authority of science in the public sphere rested on the separation and disentanglement of science from social and ethical values. This chapter argues that there is something to the first idea—that there is an important conceptual difference between normative and descriptive claims, but because of their logical structures, normative claims cannot provide sole support for descriptive claims, and vice versa. It argues that the second idea is crucially incomplete—that although there are distinctive epistemic values in science, they cannot decisively guide inference. And, finally, it argues that the third idea is inadequate as well—that we need a more complex understanding of why we grant science general epistemic authority, with multiple bases supporting that authority.
Defining and Defending Vulnerability
Authors: Martin Angela K.
Published: April 2023

This chapter presents a definition of both universal and situational vulnerability. It argues that those beings with welfare and agency interests which can potentially be frustrated should be counted as generally vulnerable. If these basic interests are frustrated, one may experience justified or unpreventable harm, unjustified harm, or harmless wrongs. This implies that not all vulnerabilities are morally relevant. Rather, the account presented here allows for a distinction between, on the one hand, manifestations of vulnerability which are unpreventable parts of life and, on the other, those manifestations which are morally problematic. Furthermore, this chapter argues that those individuals and groups with a comparatively higher risk of having their claims disregarded or unfairly considered by moral agents should be deemed situationally particularly vulnerable and be afforded additional attention and special protection.
Conclusion
Authors: Martin Angela K.
Published: April 2023

This chapter summarizes the book’s main ideas and arguments with regard to human and animal vulnerability. It identifies the specific function of vulnerability discourse—namely, directing our attention toward those individuals who need additional attention and special protection. Moreover, it addresses questions which are still open and in need of further investigation. Finally, responses and further clarifications are provided with regard to the account of vulnerability presented here, and further application fields of vulnerability discourse are fleshed out.
Mental health service diversity and work disability: associations of mental health service system characteristics and mood disorder disability pensioning in Finland
Authors: Karolaakso Tino , Autio Reija , Suontausta Petra , Leppänen Helena , Rissanen Päivi , Näppilä Turkka , Tuomisto Martti T. , Pirkola Sami
Published: April 2023

Purpose

Public mental health services (MHS) are crucial in preventing psychiatric disability pensions (DP). We studied the associations between mood disorder DP risk and the characteristics of Finnish municipalities’ MHS provision using the ESMS-R mapping tool and Finnish population registers, based on first-time granted mood disorder DPs between 2010 and 2015.

Methods

The final data set included 13,783 first-time mood disorder DP recipients and 1088 mental health service units in 104 municipalities. We focused on five different MHS types: all MHS, outpatient care provision, local services without and with gatekeeping, and centralized services. Three factors for each MHS type were studied: service resources, richness, and diversity index. Negative binomial regression models were used in the analysis.

Results

In all the municipalities, higher service richness and diversity regarding all MHS, outpatient care and local services with gatekeeping were associated with a lower DP risk. In urban municipalities, service richness was mainly associated with lower DP risk, and in semi-urban municipalities service diversity and resources were primarily associated with lower DP risk in outpatient care and local services with gatekeeping. In rural municipalities, DP risk indicated no association with MHS factors.

Conclusion

The organization and structure of MHS play a role in psychiatric disability pensioning. MHS richness and diversity are associated with lower mood disorder DP in specific societal contexts indicating their role as quality indicators for regional MHS. The diversity of service provision should be accounted for in MHS planning to offer services matching population needs.
Human skeleton behavior recognition model based on multi-object pose estimation with spatiotemporal semantics
Authors: Liu Jiaji , Mu Xiaofang , Liu Zhenyu , Li Hao
Published: April 2023

Multi-object pose estimation in surveillance scenes is challenging and inaccurate due to object motion blur and pose occlusion in video data. Targeting at the temporal dependence and coherence among video frames, this paper reconstructs a multi-object pose estimation model that integrates spatiotemporal semantics for different scales and poses of video multi-objects. The model firstly, with an end-to-end detection framework, detects multiple targets in the video. Secondly, it enhances the positioning of key points of human body using the temporal cues among video frames and designs modular components to enrich the pose information, effectively refining the pose estimation. Finally, the improved human skeleton behavior recognition model based on pose estimation is employed to recognize the classroom behaviors of students oriented to video streams. Comparison with multiple classifiers through experiments reveals that the human skeleton behavior recognition model for multi-object pose estimation combined with spatiotemporal semantics exhibits an effectively improved accuracy.
Analysis of the local heat transfer of quenching of moving metal sheets made of different materials using flat spray nozzles
Authors: Mehdi Bilal , Ryll Stephan , Specht Eckehard
Published: April 2023

Experimental investigations have been performed for the cooling of hot moving metal sheets of thickness 2 mm and 5 mm with the initial temperature of 500 °C to 800 °C by two flat spray nozzles. Tap water at room temperature is used as a coolant. Experiments are carried out for nickel, nicrofer, and aluminum alloy AA6082 with varying sheet velocity( 5,10,15 mm/s) and nozzle inclination angle (45°,65°,90°). The temperature distribution on the backside of the sheet during the cooling is recorded with a high-speed infrared camera. The recorded thermal data are used in the inverse heat conduction analysis to estimate the local heat fluxes and temperatures on the quenched surface. The thermal images obtained are used to analyze the length of the pre-cooling, transition boiling, and nucleate boiling. The maximum heat flux, the DNB temperature, and the rewetting temperature are presented for researched parameters. The nozzle inclination angle has a weak influence. The higher the velocity and the thickness of the sheet are, the higher the maximum heat flux and the shorter the pre-cooling region. The reason is that the position of the max. heat flux is shifted downstream near to impingement region.
Wild Australian magpies learn to pull intact, not broken, strings to obtain food
Authors: Johnsson Robin D. , Veillet Papillon S. , Connelly Farley , Endler John A. , Roth Timothy C. , Lesku John A.
Published: April 2023

The string-pulling paradigm is an approach commonly used in the study of animal cognition to investigate problem-solving abilities. This test involves an out-of-reach reward that can only be acquired through pulling a string. Australian magpies (Gymnorhina tibicen tyrannica) can solve cognitive tasks requiring associative and reversal learning, spatial memory, and inhibitory control. Nonetheless, whether magpies can pass a test of means-end understanding—the string-pull test—is unclear. We tested wild magpies on a string-pulling task with five configurations, including a long loose string that required several pulls to obtain food, a short string that only required a single pull to complete, and two short strings—one intact and connected to the food reward; the other broken and unable to yield food when pulled. Of the 11 magpies tested, none solved the long string task at first presentation. Two naïve birds and three, subsequently trained, birds succeeded at the short string. Once proficient at the short string, four of these five birds then solved the long string task; in addition, three learned to choose a functional, intact string over a non-functional, broken string. Overall, these observations provide evidence that Australian magpies have the ability to solve string-pulling tasks but it remains unclear whether they do so by trial-and-error or if they possess means-end understanding.

Significance statement

We found, for the first time, that wild, free-ranging Australian magpies can learn to solve different versions of a string-pulling task; a version with a short string, a long string, and two strings next to each other where one of them was broken and non-functional (broken string task). Some magpies spontaneously solved the task with the short string, where other magpies required training, and magpies only managed to solve the task with the long string after they had succeeded on the short string task. Furthermore, some of the magpies solved the broken string task but required a high number of trials to do so. Overall, our findings show that Australian magpies have the ability to solve string-pulling tasks but it remains unclear whether they do so by trial-and-error or if they understand causal relations between objects.
The Mode of Communication as a Driver of Sustainable and Equitable Asymmetric Common Pool Resource Use
Authors: Herne Kaisa , Kuyper Jonathan , Lappalainen Olli
Published: April 2023

Most experimental studies on common pool resource usage focus on situations in which actors are in symmetric positions when they use the resource. Many real-world cases do not fit this scenario because users are in asymmetric positions regarding their ability to benefit from the resource. Examples range from irrigation systems to climate change mitigation. Moreover, while there is large evidence on the effects of communication on social dilemmas, few studies focus on different modes of communication. We compare the effects of unstructured and structured communication on the provision of an infrastructure for a common pool resource and appropriation of the provided resource. Structured communication applied rules that are based on the ideals of democratic deliberation. Participants made contribution and appropriation decisions in an incentivized experiment. In the experiment, both communication and deliberation increased contributions in comparison to a baseline. Interestingly, deliberation attenuated the effect of the player position more than communication. Our results suggest that deliberation may be useful for overcoming asymmetric commons dilemmas in the field.
Cryoxcellia borchgrevinki gen. nov., sp. nov., a new parasitic X-cell species in an Antarctic nototheniid fish, the bald notothen Trematomus borchgrevinki
Authors: Evans Clive W. , Patel Selina , Matzke Nicholas J. , Millar Craig D.
Published: April 2023

X-cells were first described as an unknown cell type in northern hemisphere flatfish in 1969. Almost a decade later they were described in an Antarctic fish, the bald notothen Trematomus borchgrevinki, thus demonstrating their global distribution. Since this time, X-cells from various northern hemisphere fish species and from three other Antarctic fishes, the emerald notothen Trematomus bernacchii, the crowned notothen Trematomus scotti, and the painted notothen Nototheniops larseni have been identified as perkinsozoan parasites of the Family Xcellidae. Currently there are seven X-cell species described within this family. Here we report the morphology of X-cells isolated from the gill filaments of the bald notothen and include details of some of its division forms. Using short-read high-throughput DNA sequencing technology we have sequenced, assembled, and verified a 5347-bp region of the X-cell rRNA repeat unit that includes the complete 18S gene. In all cases, phylogenetic analyses identified this sequence as a distinct taxon and placed it among the perkinsozoan alveolates alongside other previously identified species in the X-cell family. Using a combination of morphological and genetic evidence we now describe a new X-cell genus and species, Cryoxcellia borchgrevinki gen. nov., sp. nov., from McMurdo Sound, Antarctica.
The yield of chest X-ray or ultra-low-dose chest-CT in emergency department patients suspected of pulmonary infection without respiratory symptoms or signs
Authors: van den Berk Inge A. H. , Lejeune Emile H. , Kanglie Maadrika M. N. P. , van Engelen Tjitske S. R. , de Monyé Wouter , Bipat Shandra , Bossuyt Patrick M. M. , Stoker Jaap , Prins Jan M. ,   on behalf of the OPTIMACT study group
Published: April 2023

Objective

The yield of pulmonary imaging in patients with suspected infection but no respiratory symptoms or signs is probably limited, ultra-low-dose CT (ULDCT) is known to have a higher sensitivity than Chest X-ray (CXR). Our objective was to describe the yield of ULDCT and CXR in patients clinically suspected of infection, but without respiratory symptoms or signs, and to compare the diagnostic accuracy of ULDCT and CXR.

Methods

In the OPTIMACT trial, patients suspected of non-traumatic pulmonary disease at the emergency department (ED) were randomly allocated to undergo CXR (1210 patients) or ULDCT (1208 patients). We identified 227 patients in the study group with fever, hypothermia, and/or elevated C-reactive protein (CRP) but no respiratory symptoms or signs, and estimated ULDCT and CXR sensitivity and specificity in detecting pneumonia. The final day-28 diagnosis served as the clinical reference standard.

Results

In the ULDCT group, 14/116 (12%) received a final diagnosis of pneumonia, versus 8/111 (7%) in the CXR group. ULDCT sensitivity was significantly higher than that of CXR: 13/14 (93%) versus 4/8 (50%), a difference of 43% (95% CI: 6 to 80%). ULDCT specificity was 91/102 (89%) versus 97/103 (94%) for CXR, a difference of − 5% (95% CI: − 12 to 3%). PPV was 54% (13/24) for ULDCT versus 40% (4/10) for CXR, NPV 99% (91/92) versus 96% (97/101).

Conclusion

Pneumonia can be present in ED patients without respiratory symptoms or signs who have a fever, hypothermia, and/or elevated CRP. ULDCT’s sensitivity is a significant advantage over CXR when pneumonia has to be excluded.

Clinical relevance statement

Pulmonary imaging in patients with suspected infection but no respiratory symptoms or signs can result in the detection of clinically significant pneumonia. The increased sensitivity of ultra-low-dose chest CT compared to CXR is of added value in vulnerable and immunocompromised patients.

Key Points

• Clinical significant pneumonia does occur in patients who have a fever, low core body temperature, or elevated CRP without respiratory symptoms or signs.

• Pulmonary imaging should be considered in patients with unexplained symptoms or signs of infections.

• To exclude pneumonia in this patient group, ULDCT’s improved sensitivity is a significant advantage over CXR.
Gd-EOB MRI for HCC subtype differentiation in a western population according to the 5th edition of the World Health Organization classification
Authors: Auer Timo A. , Halskov Sebastian , Fehrenbach Uli , Nevermann Nora F. , Pelzer Uwe , Mohr Raphael , Hamm Bernd , Schöning Wenzel , Horst David , Ihlow Jana , Geisel Dominik
Published: April 2023

Objectives

To investigate the value of gadoxetic acid (Gd-EOB)–enhanced magnetic resonance imaging (MRI) for noninvasive subtype differentiation of HCCs according to the 5th edition of the WHO Classification of Digestive System Tumors in a western population.

Methods

This retrospective study included 262 resected lesions in 240 patients with preoperative Gd-EOB-enhanced MRI. Subtypes were assigned by two pathologists. Gd-EOB-enhanced MRI datasets were assessed by two radiologists for qualitative and quantitative imaging features, including imaging features defined in LI-RADS v2018 and area of hepatobiliary phase (HBP) iso- to hyperintensity.

Results

The combination of non-rim arterial phase hyperenhancement with non-peripheral portal venous washout was more common in “not otherwise specified” (nos-ST) (88/168, 52%) than other subtypes, in particular macrotrabecular massive (mt-ST) (3/15, 20%), chromophobe (ch-ST) (1/8, 13%), and scirrhous subtypes (sc-ST) (2/9, 22%) (p = 0.035). Macrovascular invasion was associated with mt-ST (5/16, p = 0.033) and intralesional steatosis with steatohepatitic subtype (sh-ST) (28/32, p < 0.001). Predominant iso- to hyperintensity in the HBP was only present in nos-ST (16/174), sh-ST (3/33), and clear cell subtypes (cc-ST) (3/13) (p = 0.031). Associations were found for the following non-imaging parameters: age and sex, as patients with fibrolamellar subtype (fib-ST) were younger (median 44 years (19–66), p < 0.001) and female (4/5, p = 0.023); logarithm of alpha-fetoprotein (AFP) was elevated in the mt-ST (median 397 µg/l (74–5370), p < 0.001); type II diabetes mellitus was more frequent in the sh-ST (20/33, p = 0.027).

Conclusions

Gd-EOB-MRI reproduces findings reported in the literature for extracellular contrast-enhanced MRI and CT and may be a valuable tool for noninvasive HCC subtype differentiation.

Clinical relevance statement

Better characterization of the heterogeneous phenotypes of HCC according to the revised WHO classification potentially improves both diagnostic accuracy and the precision of therapeutic stratification for HCC.

Key Points

• Previously reported imaging features of common subtypes in CT and MRI enhanced with extracellular contrast agents are reproducible with Gd-EOB-enhanced MRI.

• While uncommon, predominant iso- to hyperintensity in the HBP was observed only in NOS, clear cell, and steatohepatitic subtypes.

• Gd-EOB-enhanced MRI offers imaging features that are of value for HCC subtype differentiation according to the 5th edition of the WHO Classification of Digestive System Tumors.
Sirolimus treatment for paediatric head and neck lymphatic malformations: a systematic review
Authors: Saibene Alberto Maria , Rosso Cecilia , Felisati Giovanni , Pignataro Lorenzo , Schindler Antonio , Ghilardi Giorgio , Colletti Giacomo , Gaffuri Michele , Mozzanica Francesco
Published: April 2023

Purpose

This PRISMA-compliant systematic review aimed to assess risks and benefits of sirolimus treatment for paediatric lymphatic malformations by focusing not only on treatment efficacy but also on possible treatment-related adverse events, and treatment combinations with other techniques.

Methods

Search criteria were applied to MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases and included all studies published up to March 2022 reporting paediatric lymphatic malformations treated with sirolimus. We selected all original studies that included treatment outcomes. After the removal of duplicates, selection of abstracts and full-text articles, and quality assessment, we reviewed eligible articles for patient demographics, lymphatic malformation type, size or stage, site, clinical response rates, sirolimus administration route and dose, related adverse events, follow-up time, and concurrent treatments.

Results

Among 153 unique citations, 19 studies were considered eligible, with reported treatment data for 97 paediatric patients. Most studies (n = 9) were case reports. Clinical response was described for 89 patients, in whom 94 mild-to-moderate adverse events were reported. The most frequently administered treatment regimen was oral sirolimus 0.8 mg/m2 twice a day, with the aim of achieving a blood concentration of 10–15 ng/mL.

Conclusion

Despite promising results for sirolimus treatment in lymphatic malformation, the efficacy and safety profile of remains unclear due to the lack of high-quality studies. Systematic reporting of known side effects, especially in younger children, should assist clinicians in minimising treatment-associated risks. At the same time, we advocate for prospective multicentre studies with minimum reporting standards to facilitate improved candidate selection.
Autoimmune encephalitis: recent clinical and biological advances
Authors: Varley James A. , Strippel Christine , Handel Adam , Irani Sarosh R.
Published: April 2023

In 2015, we wrote a review in The Journal of Neurology summarizing the field of autoantibody-associated neurological diseases. Now, in 2023, we present an update of the subject which reflects the rapid expansion and refinement of associated clinical phenotypes, further autoantibody discoveries, and a more detailed understanding of immunological and neurobiological pathophysiological pathways which mediate these diseases. Increasing awareness around distinctive aspects of their clinical phenotypes has been a key driver in providing clinicians with a better understanding as to how these diseases are best recognized. In clinical practice, this recognition supports the administration of often effective immunotherapies, making these diseases ‘not to miss’ conditions. In parallel, there is a need to accurately assess patient responses to these drugs, another area of growing interest. Feeding into clinical care are the basic biological underpinnings of the diseases, which offer clear pathways to improved therapies toward enhanced patient outcomes. In this update, we aim to integrate the clinical diagnostic pathway with advances in patient management and biology to provide a cohesive view on how to care for these patients in 2023, and the future.
Safety and effectiveness of ataluren in patients with nonsense mutation DMD in the STRIDE Registry compared with the CINRG Duchenne Natural History Study (2015–2022): 2022 interim analysis
Authors: Mercuri Eugenio , Osorio Andrés Nascimento , Muntoni Francesco , Buccella Filippo , Desguerre Isabelle , Kirschner Janbernd , Tulinius Már , de Resende Maria Bernadete Dutra , Morgenroth Lauren P. , Gordish-Dressman Heather , Johnson Shelley , Kristensen Allan , Werner Christian , Trifillis Panayiota , Henricson Erik K. , McDonald Craig M. ,   the STRIDE and CINRG DNHS investigators
Published: April 2023

Objective

Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, international, multicenter registry of real-world ataluren use in individuals with nonsense mutation Duchenne muscular dystrophy (nmDMD) in clinical practice. This updated interim report (data cut-off: January 31, 2022), describes STRIDE patient characteristics and ataluren safety data, as well as the effectiveness of ataluren plus standard of care (SoC) in STRIDE versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS).

Methods

Patients are followed up from enrollment for at least 5 years or until study withdrawal. Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established predictors of disease progression.

Results

As of January 31, 2022, 307 patients were enrolled from 14 countries. Mean (standard deviation [SD]) ages at first symptoms and at genetic diagnosis were 2.9 (1.7) years and 4.5 (3.7) years, respectively. Mean (SD) duration of ataluren exposure was 1671 (56.8) days. Ataluren had a favorable safety profile; most treatment-emergent adverse events were mild or moderate and unrelated to ataluren. Kaplan–Meier analyses demonstrated that ataluren plus SoC significantly delayed age at loss of ambulation by 4 years (p < 0.0001) and age at decline to %-predicted forced vital capacity of < 60% and < 50% by 1.8 years (p = 0.0021) and 2.3 years (p = 0.0207), respectively, compared with SoC alone.

Conclusion

Long-term, real-world treatment with ataluren plus SoC delays several disease progression milestones in individuals with nmDMD. NCT02369731; registration date: February 24, 2015.
Semiautomatic assessment of endothelial density and morphology in organ-cultured corneas — potential predictors for transplantation suitability and clinical outcome?
Authors: Filev Filip , Stein Mathias , Schultheiss Maximilian , Fitzek Antonia D. E. , Feuerstake Jana , Engel Oliver , Hellwinkel Olaf J. C.
Published: April 2023

Background

The quality of the endothelial cell layer is a major criterion for the approval of organ-cultured human donor-corneas for transplantation. We wanted to compare the predictive capacities of initial endothelial density and endothelium cell morphology for the approval of donor corneas for transplantation and for the clinical outcome after transplantation.

Methods

The endothelial density and endothelium morphology in organ culture were examined by semiautomatic assessment of 1031 donor corneas. We performed a statistical analysis for correlations of donor-data and cultivation parameters regarding their predictive capacities for the final approval of donor corneas for transplantation and the clinical outcome of 202 transplanted patients.

Results

Corneal endothelium cell density proved to be the only parameter with a certain predictive capacity with regard to the final decision, whether donor corneas are suitable for transplantation — however, the correlation was low (area under the curve [AUC] = 0.655). Endothelial cell morphology lacked any predictive power (AUC = 0.597). The clinical outcome regarding visual acuity seemed to be largely independent from both corneal endothelial cell density and morphology. Sub-analyses on transplanted patients stratified for their diagnoses vindicated these findings.

Conclusions

Higher endothelial density (above a cut-off level of 2000 cells/mm2), as well as better endothelial morphology do not seem to be critical for transplant-corneal functionality in organ culture and up to 2 years after transplantation. Comparable long-term studies on graft survival are recommended to determine, whether the present endothelial density cut-off levels might be too stringent.
Promising efficacy of immune checkpoint inhibitor plus chemotherapy for thoracic SMARCA4-deficient undifferentiated tumor
Authors: Lin Ying , Yu Bo , Sun Haifeng , Zhang Hongyu , Hu Zhihuang , Zhang Yao , Wu Zhenhua , Sun Si , Zhao Xinmin , Yu Hui , Wu Xianghua , Li Yuan , Wang Jialei , Wang Huijie
Published: April 2023

Purpose

Thoracic SMARCA4-deficient undifferentiated tumor (SD-UT) is a highly aggressive disease that is nosologically related to but distinct from SMARCA4-deficient non-small cell lung cancer (SD-NSCLC). No standard treatment guidelines were established for SD-UT. This research explored the efficacy of different treatments in SD-UT, and the prognostic, clinicopathologic and genomic difference between SD-UT and SD-NSCLC.

Materials and methods

Information of 25 SD-UT and 22 SD-NSCLC patients diagnosed and treated in Fudan University Shanghai Cancer Center from January, 2017 to September, 2022 was analyzed.

Results

SD-UT was similar to SD-NSCLC in characteristics of onset age, male prevalence, heavy smoking history and metastatic pattern. SD-UT showed a rapid relapse pattern after radical therapy. For Stage IV SD-UT patients, immune checkpoint inhibitor (ICI) plus chemotherapy significantly improved median progression-free survival (PFS) compared to traditional chemotherapy as first-line treatment (26.8 vs. 2.73 months, p = 0.0437), while objective response rates of two arms were comparable (71.4% vs. 66.7%). No significant survival differences were observed between SD-UT and SD-NSCLC under similar treatment settings. SD-UT or SD-NSCLC patients receiving ICI in the first line had significantly prolonged OS than those with ICI in the latter lines or without ICI treatment throughout clinical courses. Genetic study found frequent SMARCA4, TP53 and LRP1B mutations in SD-UT.

Conclusion

To the best of our knowledge, this is the largest series to date to compare the efficacy of ICI-based treatment to chemotherapy and document frequent mutations of LRP1B in SD-UT. ICI plus chemotherapy is an effective strategy for Stage IV SD-UT.
The omics era: a nexus of untapped potential for Mendelian chromatinopathies
Authors: Nava Aileen A. , Arboleda Valerie A.
Published: April 2023

The OMICs cascade describes the hierarchical flow of information through biological systems. The epigenome sits at the apex of the cascade, thereby regulating the RNA and protein expression of the human genome and governs cellular identity and function. Genes that regulate the epigenome, termed epigenes, orchestrate complex biological signaling programs that drive human development. The broad expression patterns of epigenes during human development mean that pathogenic germline mutations in epigenes can lead to clinically significant multi-system malformations, developmental delay, intellectual disabilities, and stem cell dysfunction. In this review, we refer to germline developmental disorders caused by epigene mutation as “chromatinopathies”. We curated the largest number of human chromatinopathies to date and our expanded approach more than doubled the number of established chromatinopathies to 179 disorders caused by 148 epigenes. Our study revealed that 20.6% (148/720) of epigenes cause at least one chromatinopathy. In this review, we highlight key examples in which OMICs approaches have been applied to chromatinopathy patient biospecimens to identify underlying disease pathogenesis. The rapidly evolving OMICs technologies that couple molecular biology with high-throughput sequencing or proteomics allow us to dissect out the causal mechanisms driving temporal-, cellular-, and tissue-specific expression. Using the full repertoire of data generated by the OMICs cascade to study chromatinopathies will provide invaluable insight into the developmental impact of these epigenes and point toward future precision targets for these rare disorders.
Gut microbiota composition and function in pregnancy as determinants of prediabetes at two-year postpartum
Authors: Houttu Noora , Benchraka Chouaib , Lotankar Mrunalini , Muhli Ella , Niinikoski Harri , Lahti Leo , Laitinen Kirsi
Published: April 2023

Aims

Deep metagenomics offers an advanced tool for examining the relationship between gut microbiota composition and function and the onset of disease; in this case, does the composition and function of gut microbiota during pregnancy differ in women who develop prediabetes and those who do not at two-year postpartum, and whether the gut microbiota composition associates with glycemic traits.

Methods

In total, 439 women were recruited in early pregnancy. Gut microbiota was assessed by metagenomics analysis in early (13.9 ± 2.0 gestational weeks) and late pregnancy (35.1 ± 1.0 gestational weeks). Prediabetes was determined using American Diabetes Association criteria as fasting plasma glucose 5.6–6.9 mmol/l analyzed by an enzymatic hexokinase method. Of the women, 39 (22.1%) developed prediabetes by two-year postpartum.

Results

The relative abundances of Escherichia unclassified (FDR < 0.05), Clostridiales bacterium 1_7_ 47FAA (FDR < 0.25) and Parabacteroides (FDR < 0.25) were higher, and those of Ruminococcaceae bacterium D16 (FDR < 0.25), Anaerotruncus unclassified (FDR < 0.25) and Ruminococcaceae noname (FDR < 0.25) were lower in early pregnancy in those women who later developed prediabetes. In late pregnancy, Porphyromonas was higher and Ruminococcus sp 5_1_39BFAA was lower in prediabetes (FDR < 0.25). Furthermore, fasting glucose concentrations associated inversely with Anaerotruncus unclassified in early pregnancy and directly with Ruminococcus sp 5_1_39BFAA in late pregnancy (FDR < 0.25). α-Diversity or β-diversity did not differ significantly between the groups. Predictions of community function during pregnancy were not associated with prediabetes.

Conclusions

Our study shows that some bacterial species during pregnancy contributed to the onset of prediabetes within two-year postpartum. These were attributable primarily to a lower abundance of short-chain fatty acids-producing bacteria.
Plasma concentrations of anti-inflammatory cytokine TGF-β are associated with hippocampal structure related to explicit memory performance in older adults
Authors: Raschick Matthias , Richter Anni , Fischer Larissa , Knopf Lea , Schult Annika , Yakupov Renat , Behnisch Gusalija , Guttek Karina , Düzel Emrah , Dunay Ildiko Rita , Seidenbecher Constanze I. , Schraven Burkhart , Reinhold Dirk , Schott Björn H.
Published: April 2023

Human cognitive abilities, and particularly hippocampus-dependent memory performance typically decline with increasing age. Immunosenescence, the age-related disintegration of the immune system, is increasingly coming into the focus of research as a considerable factor contributing to cognitive decline. In the present study, we investigated potential associations between plasma levels of pro- and anti-inflammatory cytokines and learning and memory performance as well as hippocampal anatomy in young and older adults. Plasma concentrations of the inflammation marker CRP as well as the pro-inflammatory cytokines IL-6 and TNF-α and the anti-inflammatory cytokine TGF-β1 were measured in 142 healthy adults (57 young, 24.47 ± 4.48 years; 85 older, 63.66 ± 7.32 years) who performed tests of explicit memory (Verbal Learning and Memory Test, VLMT; Wechsler Memory Scale, Logical Memory, WMS) with an additional delayed recall test after 24 h. Hippocampal volumetry and hippocampal subfield segmentation were performed using FreeSurfer, based on T1-weighted and high-resolution T2-weighted MR images. When investigating the relationship between memory performance, hippocampal structure, and plasma cytokine levels, we found that TGF-β1 concentrations were positively correlated with the volumes of the hippocampal CA4–dentate gyrus region in older adults. These volumes were in turn positively associated with better performance in the WMS, particularly in the delayed memory test. Our results support the notion that endogenous anti-inflammatory mechanisms may act as protective factors in neurocognitive aging.
Correlation analysis of agricultural drought risk on wet farming crop and meteorological drought index in the tropical-humid region
Authors: Irawan Amalia Nafisah Rahmani , Komori Daisuke , Hendrawan Vempi Satriya Adi
Published: April 2023

In the tropical-humid region, wet farming crops (e.g., paddy) are a common agricultural commodity with a high-water requirement. Usually planted in the Asia monsoon region with a high precipitation rate, these crops are divided into the wet cropping season and the dry cropping season. During the dry cropping season, they are particularly vulnerable to agricultural drought caused by the decrease in precipitation. This study used Indonesia as a case study and is aimed at assessing the agricultural drought risk on a wet farming crop during the dry cropping season by examining the correlation between the drought hazard and its risk. For hazard assessment, Standardized Precipitation Index (SPI) was used to assess the agricultural drought, by using the Global Satellite Mapping of Precipitation (GSMaP) which has 0.1° × 0.1° spatial resolution. The result of correlation analysis between the SPI and drought-affected areas on a city scale showed that SPI-3 in August is the most suitable timescale to assess the agricultural drought in Indonesia. The agricultural drought risk assessment was conducted on the grid scale, where the crop yield estimation model was developed with the help of Normalized Difference Vegetation Index (NDVI). Based on the correlation analysis between SPI-3 and the detrended crop yield as drought risk indicators, the higher yield loss was found in the area above the threshold value (r-value ≤ 0.6) indicating that those areas were more vulnerable to drought, while the area below the threshold value has lower crop yield loss even in the area that was hit by the most severe drought, because the existing irrigation system was able to resist the drought’s impact on crop yield loss.
On the homeotypes of kobellite
Authors: Makovicky Emil , Balić-Žunić Tonči
Published: April 2023

Kobellite is a Pb-Bi-Sb sulfosalt with minor amounts of (Cu, Fe) and with the crystal structure composed of two types of rods, one of which has unusual lateral extensions (‘lobes’), which depart from the usual lozenge-shaped rod cross-section in sulfosalts. Several Pb-Bi-Sb and Pb-Sb-rich sulfosalts form a small group built on similar principles. Some of them are related by homology (e.g., izoklakeite), and differ by the perpendicular dimensions of rods (length and multiplicity of atomic layers in a rod; e.g., sterryite), and especially by different combinations of archetypes and archetype portions which participate in the rods (PbS archetype and the two orientations of SnS archetype). The present article summarizes and discusses the published data on the group. Homeotypism makes the group interesting and potentially a fertile source of further structural varieties.