bluuebunny/crossref_metadata_2025 huggingface dataset:
Star clusters forming in a low-metallicity starburst – rapid self-enrichment by (very) massive stars
Authors: Lahén Natalia , Naab Thorsten , Szécsi Dorottya
Published: March 2024

Stellar winds of massive ($\gtrsim 9\, \mathrm{M_\odot }$) and very massive ($\gtrsim 100\, \mathrm{M_\odot }$) stars may play an important role in the metal-enrichment during the formation of star clusters. With novel high-resolution hydrodynamical griffin-project simulations, we investigate the rapid recycling of stellar wind-material during the formation of massive star clusters up to $M_\mathrm{cluster}\sim 2\times 10^5\, \mathrm{M_\odot }$ in a low-metallicity dwarf galaxy starburst. The simulation realizes new stars from a stellar initial mass function (IMF) between $0.08$ and $\sim 400\, \mathrm{M_\odot }$ and follows stellar winds, radiation and supernova-feedback of single massive stars with evolution tracks. Star clusters form on time-scales less than ∼5 Myr, and their supernova-material is very inefficiently recycled. Stellar wind-material, however, is trapped in massive clusters resulting in the formation of stars self-enriched in Na, Al, and N within only a few Myr. Wind-enriched (second population, 2P) stars can be centrally concentrated in the most massive clusters ($\gtrsim 10^4\, \mathrm{M_\odot }$) and the locked wind-material increases approximately as $M_\mathrm{cluster}^{2}$. These trends resemble the characteristics of observed 2P stars in globular clusters (GCs). We fit scaling relations to the lognormal distributed wind-mass fractions and extrapolate to possible GC progenitors of $M_\mathrm{cluster}=10^7\, \mathrm{M_\odot }$ to investigate whether a dominant 2P could form. This can only happen if the IMF is well-sampled, single massive stars produce at least a factor of a few more enriched winds, for example, through a top-heavy IMF, and a significant fraction of the first population (unenriched) stars is lost during cluster evolution.
Characterization of the ESPRESSO line-spread function and improvement of the wavelength calibration accuracy
Authors: Schmidt Tobias M , Bouchy François
Published: March 2024

Achieving a truly accurate wavelength calibration of high-dispersion echelle spectrographs is a challenging task but crucially needed for certain science cases, e.g. to test for a possible variation of the fine-structure constant in quasar spectra. One of the spectrographs best suited for this mission is Very Large Telescope/Echelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observation (ESPRESSO). Nevertheless, previous studies have identified significant discrepancies between the classical wavelength solutions and the one derived independently from the laser frequency comb. The dominant parts of these systematics were intra-order distortions, most-likely related to a deviation of the instrumental line-spread function from the assumed Gaussian shape. Here, we therefore present a study focused on a detailed modelling of the ESPRESSO instrumental line-spread function. We demonstrate that it is strongly asymmetric, non-Gaussian, different for the two slices and fibres, and varies significantly along the spectral orders. Incorporating the determined non-parametric model in the wavelength calibration process drastically improves the wavelength calibration accuracy, reducing the discrepancies between the two independent wavelength solutions from $50\,\rm{m\,s^{-1}}$ to about $10\, \rm{m\,s^{-1}}$. The most striking success is, however, that the different fibres and slices now provide fully consistent measurements with a scatter of just a couple m s−1. This demonstrates that the instrument-related systematics can be nearly eliminated over most of the spectral range by properly taking into account the complex shape of the instrumental line-spread function and paves the way for further optimizations of the wavelength calibration process.
Prevalence and characteristics of genetic disease in adult kidney stone formers
Authors: Anderegg Manuel A , Olinger Eric G , Bargagli Matteo , Geraghty Rob , Taylor Lea , Nater Alexander , Bruggmann Rémy , Sayer John A , Vogt Bruno , Schaller André , Fuster Daniel G
Published: March 2024

Background

Molecular mechanisms of kidney stone formation remain unknown in most patients. Previous studies have shown a high heritability of nephrolithiasis, but data on the prevalence and characteristics of genetic disease in unselected adults with nephrolithiasis are lacking. This study was conducted to fill this important knowledge gap.

Methods

We performed whole exome sequencing in 787 participants in the Bern Kidney Stone Registry, an unselected cohort of adults with one or more past kidney stone episodes [kidney stone formers (KSFs)] and 114 non-kidney stone formers (NKSFs). An exome-based panel of 34 established nephrolithiasis genes was analysed and variants assessed according to American College of Medical Genetics and Genomics criteria. Pathogenic (P) or likely pathogenic (LP) variants were considered diagnostic.

Results

The mean age of KSFs was 47 ± 15 years and 18% were first-time KSFs. A Mendelian kidney stone disease was present in 2.9% (23/787) of KSFs. The most common genetic diagnoses were cystinuria (SLC3A1, SLC7A9; n = 13), vitamin D-24 hydroxylase deficiency (CYP24A1; n = 5) and primary hyperoxaluria (AGXT, GRHPR, HOGA1; n = 3). Of the KSFs, 8.1% (64/787) were monoallelic for LP/P variants predisposing to nephrolithiasis, most frequently in SLC34A1/A3 or SLC9A3R1 (n = 37), CLDN16 (n = 8) and CYP24A1 (n = 8). KSFs with Mendelian disease had a lower age at the first stone event (30 ± 14 versus 36 ± 14 years; P = .003), were more likely to have cystine stones (23.4% versus 1.4%) and less likely to have calcium oxalate monohydrates stones (31.9% versus 52.5%) compared with KSFs without a genetic diagnosis. The phenotype of KSFs with variants predisposing to nephrolithiasis was subtle and showed significant overlap with KSFs without diagnostic variants. In NKSFs, no Mendelian disease was detected and LP/P variants were significantly less prevalent compared with KSFs (1.8% versus 8.1%).

Conclusion

Mendelian disease is uncommon in unselected adult KSFs, yet variants predisposing to nephrolithiasis are significantly enriched in adult KSFs.
The safety of a low-protein diet in older adults with advanced chronic kidney disease
Authors: Windahl Karin , Chesnaye Nicholas C , Irving Gerd Faxén , Stenvinkel Peter , Almquist Tora , Lidén Maarit Korkeila , Drechsler Christiane , Szymczak Maciej , Krajewska Magdalena , de Rooij Esther , Torino Claudia , Porto Gaetana , Caskey Fergus J , Wanner Christoph , Jager Kitty J , Dekker Friedo W , Evans Marie ,   the EQUAL study investigators, Windahl Karin , Chesnaye Nicholas C , Irving Gerd Faxén , Stenvinkel Peter , Almquist Tora , Lidén Maarit Korkeila , Drechsler Christiane , Szymczak Maciej , Krajewska Magdalena , de Rooij Esther , Torino Claudia , Porto Gaetana , Caskey Fergus J , Wanner Christoph , Jager Kitty J , Dekker Friedo W , Evans Marie
Published: March 2024

Background

A low-protein diet (LPD) is recommended to patients with advanced chronic kidney disease (CKD), whereas geriatric guidelines recommend a higher amount of protein. The aim of this study was to evaluate the safety of LPD treatment in older adults with advanced CKD.

Methods

The EQUAL study is a prospective, observational study including patients ≥65 years of age with an incident estimated glomerular filtration rate <20 ml/min/1.73 m2 in six European countries with follow-up through 6 years. Nutritional status was assessed by a 7-point subjective global assessment (SGA) every 3–6 months. Prescribed diet (g protein/kg of bodyweight) was recorded on every study visit; measured protein intake was available in three countries. Time to death and decline in nutritional status (SGA decrease of ≥2 points) were analysed using marginal structural models with dynamic inverse probability of treatment and censoring weights.

Results

Of 1738 adults (631 prescribed LPD at any point during follow-up), there were 1319 with repeated SGA measurements, of which 267 (20%) decreased in SGA ≥2 points and 565 (32.5%) who died. There was no difference in survival or decrease in nutritional status for patients prescribed a LPD ≤0.8 g/kg ideal bodyweight {odds ratio [OR] for mortality 1.15 [95% confidence interval (CI) 0.86–1.55)] and OR for decrease in SGA 1.11 [95% CI 0.74–1.66]} in the adjusted models. In patients prescribed a LPD <0.6 g/kg ideal bodyweight, the results were similar. There was a significant interaction with LPD and older age >75 years, lower SGA and higher comorbidity burden for both mortality and nutritional status decline.

Conclusions

In older adults with CKD approaching end-stage kidney disease, a traditional LPD prescribed and monitored according to routine clinical practice in Europe appears to be safe.
Strategic behaviours in a labour market with mobility-restricting contractual provisions: evidence from the National Hockey League
Authors: Fumarco Luca , Longley Neil , Palermo Alberto , Rossi Giambattista
Published: March 2024

We follow workers’ performance along an unbalanced panel dataset over multiple years and study how performance varies at the end of fixed-term contracts, in a labour market where some people face a mobility-restricting clause (i.e. a noncompete clause). Focusing on the labour market of the National Hockey League, we analyse players’ performance data and contracts with a fixed-effects estimator to address empirical limitations in previous studies. We find that, on average, National Hockey League players’ performance does not vary. However, our estimations detect substantially heterogeneous behaviours, depending on tenure, perceived expected performance, and mobility. Only younger players (i.e. restricted free agents) with high expected mobility but low expected performance tend to behave strategically and perform better. Differently, older players (i.e. unrestricted free agents) with high expected mobility tend to underperform, as the option of moving back to European tournaments is more appealing.
Self-Organisation in Gabbroic Cumulates: a New Patterning Mechanism Driven by Differential Migration of Immiscible Liquids in a Crystal Mush?
Authors: Holness Marian B
Published: March 2024

Self-organisation in plutonic igneous rocks has been suggested to form by a variety of mechanisms including oscillatory nucleation and growth, competitive particle growth (CPG), and preferential dissolution and reprecipitation during fluid infiltration enhanced by compaction, with driving forces including reduction of the interfacial energy budget by either Ostwald ripening or because the energy of boundaries between two grains of the same mineral is less than that between two grains of different minerals. An investigation of the Stillwater inch-scale layering shows that the CPG patterning mechanism leaves a characteristic microstructural signature preserving evidence for a highly interconnected melt in textural equilibrium and slow super- and sub-solidus cooling; such a signature is also preserved in chromite-bearing fine-scale layers in the Bushveld intrusion. The cm-scale (centimetre-scale) micro-rhythmic layering of the Skaergaard intrusion, superimposed on single modally graded layers, does not have these microstructural features. Furthermore, the energy of all relevant interphase grain boundaries in the Skaergaard gabbros is less than that of grain boundaries involving only one mineral, viscous compaction was not a significant process in the Skaergaard intrusion, and patterning by oscillatory nucleation and growth is precluded by the fact that the micro-rhythmic layering is superimposed on modally graded layers formed by sedimentation. A new patterning mechanism is proposed, operational only in intrusions in which the interstitial liquid of the crystal mush intersects a binode and splits into two immiscible conjugates. Cm-scale separation of the immiscible conjugate liquids in a compositionally graded mush, due to both gravity and capillary forces, leads to layering due to differences in their wetting properties. The positive feedback required for pattern formation is due to the two immiscible conjugates predominantly crystallising the minerals which they preferentially wet.
Sub-arc Mantle Heterogeneity of the Northern Luzon Volcanic Arc: Mineral and Whole Rock Compositional Variability in Mantle Xenoliths from Lutao Island
Authors: Shellnutt J Gregory , Yeh Meng-Wan , Lee Tung-Yi , Iizuka Yoshiyuki , Chen Wei-Yu , Prasanth M P Manu
Published: March 2024

Mantle xenoliths hosted in volcanic rocks from the island of Lutao offer a glimpse into the nature of the mantle beneath the northern Luzon volcanic arc. The xenoliths are spinel-bearing and composed mostly of harzburgite with one lherzolite and one olivine orthopyroxenite. The olivine (Fo92.5–88.9), orthopyroxene (Mg# = 94.6–89.2), and clinopyroxene (Wo49.1–38.1En57.0–45.4Fs3.0–11.0) compositions are similar to those of abyssal peridotites. The spinel compositions are variable and can be principally divided into high-Al (Cr# < 45) and low-Al (Cr# > 45) groupings. The whole rock compositions are similar to abyssal peridotite (Al2O3 = 0.95–2.07 wt %; Mg# = 88.5–90.9) and have U-shaped chondrite normalized rare earth element patterns. The Sr-Nd isotopes of the xenoliths are broadly chondritic (87Sr/86Sri = 0.704400–0.707908; εNd(t) = 0.0 − +1.5). The two-pyroxene equilibrium temperatures range from 900 to 1200 °C with the majority of temperature estimates >1000 °C. The olivine-orthopyroxene-spinel oxygen barometry estimates yielded ΔFMQ values from 0 to +2 and correspond to moderately oxidizing to oxidizing conditions. The xenoliths are likely derived from the Philippine Sea Plate lithospheric mantle that was modified by melt extraction and/or fluid enrichment processes. Trace element and isotopic mixing modeling indicate that 1–2% contamination by subducted South China Sea sediment can explain the Sr-Nd isotopic enrichment and Th and U elemental variability within the xenoliths assuming an initial composition similar to enriched depleted mid-ocean ridge mantle (E-DMM). The anomalously high two-pyroxene equilibrium temperatures of the Lutao xenoliths relative to other regions of the northern Luzon volcanic arc (Iraya <1000 °C) indicate that they were affected by a high-temperature event that was likely a consequence of recent intra-arc rifting that occurred after collision (<6 Ma) between the Luzon arc and the Eurasian margin.
Plastid retrograde signaling: A developmental perspective
Authors: Loudya Naresh , Barkan Alice , López-Juez Enrique
Published: March 2024

Chloroplast activities influence nuclear gene expression, a phenomenon referred to as retrograde signaling. Biogenic retrograde signals have been revealed by changes in nuclear gene expression when chloroplast development is disrupted. Research on biogenic signaling has focused on repression of Photosynthesis-Associated Nuclear Genes (PhANGs), but this is just one component of a syndrome involving altered expression of thousands of genes involved in diverse processes, many of which are upregulated. We discuss evidence for a framework that accounts for most of this syndrome. Disruption of chloroplast biogenesis prevents the production of signals required to progress through discrete steps in the program of photosynthetic differentiation, causing retention of juvenile states. As a result, expression of PhANGs and other genes that act late during photosynthetic differentiation is not initiated, while expression of genes that act early is retained. The extent of juvenility, and thus the transcriptome, reflects the disrupted process: lack of plastid translation blocks development very early, whereas disruption of photosynthesis without compromising plastid translation blocks development at a later stage. We discuss implications of these and other recent observations for the nature of the plastid-derived signals that regulate photosynthetic differentiation and the role of GUN1, an enigmatic protein involved in biogenic signaling.
Association between visceral adipose tissue and asthma based on the NHANES and Mendelian randomization study
Authors: Yin Pan , Tao Shiran , Xing Zixuan , Luo Shenglin , Yang Zhiluo , Xue Zihan , Yang Ruida , Liu Luyu , Wu Shaobo , Ge Juan
Published: March 2024

Background

Obesity is a crucial risk factor for asthma. Observational studies have examined the association between abdominal obesity and asthma symptoms. This study aimed to investigate the causal relationship between visceral adipose tissue (VAT) and asthma and its potential as an independent indicator.

Methods

This study utilized data from the National Health and Nutrition Examination Survey spanning 2011–8. Multivariable logistic regression and stratified variable selection were employed to identify associations between asthma and VAT. Moreover, a two-sample Mendelian randomization analysis, using 221 genetic variants as instrumental variables, was conducted to assess this relationship further.

Results

Our findings indicated that individuals with higher VAT levels were more likely to develop asthma. Visceral obesity remained a significant risk factor for asthma after adjusting for demographic characteristics. Genetic predictions suggest a positive association between VAT and an elevated risk of asthma (odds ratio [OR] = 1.393, 95% confidence interval [CI]: 1.266–1.534, and P = 1.43E−11). No significant polymorphisms were detected using the Mendelian randomization-Egger intercept test.

Conclusions

This study presents potential evidence supporting the causal role of VAT in asthma development. Furthermore, the findings from the Mendelian randomization analysis further reinforce the relationship between VAT and asthma risk.
Not Whether to Coordinate, But How: Concerns and Mechanism Choice Under a Mandate for Inter-Agency Coordination
Authors: Milman Anita , Roberts Michael , Walsh Amber , Blomquist William
Published: March 2024

A critical question in relation to inter-agency coordination is not only whether, but how, to coordinate. This question is particularly salient when agencies are subject to a top-down mandate. While inter-agency coordination can provide multiple benefits, agencies frequently have concerns about the potential risks of coordination. Differing coordination mechanisms may reduce or exacerbate those concerns. Depending on their coordination concerns, agencies will be inclined to favor certain mechanisms over others. Examination of the implementation of California’s Sustainable Groundwater Management Act, which mandates local agency coordination, indicates that coordination mechanism selection is influenced by which combination of concerns agencies hold, with autonomy considerations taking priority over other concerns. These findings suggest opportunities to improve the explanatory power of theories of inter-agency coordination by incorporating potential hierarchies of concerns, their distribution across the multiple agencies tasked with coordinating, and configurational effects. To this end, we propose a contingency theory of agency concerns and coordination mechanism choice under a mandate to coordinate.
Pharmacological interventions for early-stage frozen shoulder: a systematic review and network meta-analysis
Authors: Berner Juan Enrique , Nicolaides Marios , Ali Stephen , Pafitanis Georgios , Preece Jane , Hopewell Sally , Nanchahal Jagdeep
Published: March 2024

Objectives

To evaluate the efficacy of pharmacological interventions for treating early-stage, pain predominant, adhesive capsulitis, also known as frozen shoulder.

Methods

We performed a systematic review in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Searches were conducted on MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials on 24 February 2022. Outcomes were shoulder pain, shoulder function and range of movement. Synthesis involved both qualitative analysis for all studies and pairwise meta-analyses followed by a network meta-analysis for randomized controlled trials (RCTs).

Results

A total of 3252 articles were found, of which 31 met inclusion criteria, and 22 of these were RCTs. IA injection of CS (8 RCTs, 340 participants) and IA injection of platelet-rich plasma (PRP) (3 RCTs, 177 participants) showed benefit at 12 weeks compared with physical therapy in terms of shoulder pain and function, while oral NSAIDs (2 RCTs, 44 participants) and IA injection of hyaluronate (2 RCTs, 42 participants) did not show a benefit. Only IA PRP showed benefit over physical therapy for shoulder range of movement.

Conclusion

These results shows that IA CS and IA PRP injections are beneficial for early-stage frozen shoulder. These findings should be appraised with care considering the risk of bias, heterogeneity and inconsistency of the included studies. We believe that research focused on early interventions for frozen shoulder could improve patient outcomes and lead to cost-savings derived from avoiding long-term disability. Further well-designed studies comparing with standardized physical therapy or placebo are required to improve evidence to guide management.
Prevalence, characteristics, and outcome of subclinical vasculitis in polymyalgia rheumatica: a retrospective cohort study
Authors: Moreel Lien , Boeckxstaens Lennert , Betrains Albrecht , Smans Timo , Molenberghs Geert , Van Laere Koen , De Langhe Ellen , Vanderschueren Steven , Blockmans Daniel
Published: March 2024

Objectives

Two recent meta-analyses reported subclinical vasculitis in 22–23% of patients with PMR. We aimed to evaluate the prevalence, characteristics, and outcome of subclinical vasculitis among our PMR patients.

Methods

Consecutive patients with GCA/PMR spectrum disease with isolated PMR symptoms who underwent FDG PET imaging between 2003 and 2020 and who were followed for ≥6 months, were included retrospectively. Vasculitis was defined as FDG uptake ≥grade 2 in any vessel.

Results

We included 337 patients, of whom 31 (9%) with subclinical vasculitis. Among those with subclinical vasculitis, 21 (58%) had isolated large vessel vasculitis, 3 (10%) had isolated cranial vasculitis and 7 (23%) had both cranial and large vessel vasculitis. The glucocorticoid (GC) starting dose and GC doses during follow-up were higher in those with subclinical vasculitis until 12 months after diagnosis (P < 0.001). There was no difference in the duration of GC treatment (25 vs 20 months, P = 0.187). Cox proportional hazard regression analyses showed no difference in the proportion of patients able to stop GC (HR 0.78 [95% CI 0.49–1.25], P = 0.303) and in the proportion of patients with relapse (HR 0.82 [95%CI 0.50–1.36], P = 0.441).

Conclusion

Only 9% of our PMR patients had subclinical vasculitis with a predilection for large vessel vasculitis. There were no differences in relapse rate and duration of GC treatment, however, those with subclinical vasculitis received higher GC doses until 12 months after diagnosis. Prospective interventional trials are needed to evaluate the outcome of PMR patients with and without subclinical vasculitis treated with a similar GC protocol.
Illegal products containing selective androgen receptor modulators purchased online from Italy: health risks for consumers
Authors: Gaudiano Maria Cristina , Aureli Federica , Manna Livia , Borioni Anna , Maccelli Alessandro , Raimondo Mariangela , De Giorgi Donato , Bartolomei Monica
Published: March 2024

Background

Selective androgen receptor modulators (SARMs) are small synthetic drug molecules that are still not approved as medicine in Europe or the United States but are sold on illegal websites to improve sport performance, particularly bodybuilding.

Aim

To address the quality issues of illegal SARM products and their increasing diffusion in Italy with their potential health risks for consumers.

Methods

Web-based tools were used to investigate retail websites, trending searches, and information exchange via social media. Thirteen SARM products, purchased on retail websites accessible from Italy, were subject to visual inspection and chemical analysis by mass spectrometry and quantitative nuclear magnetic resonance.

Outcomes

The primary outcome was demonstration of additional health risks due to the illicit presence of other active ingredients, contamination, and misdosage in SARM products sold on the internet. The secondary outcome was to show the increasing trend of interest in Italy for these products.

Results

Most websites reported misleading information; specifically, the statement “for research only” was reported notwithstanding indications on dosage and training phases. The trending search showed that interest toward SARMs increased in Italy in the last years. The use of these products is clearly encouraged by the emerging phenomenon of “broscience” as revealed in socials. Visual inspection evidenced nonconform labeling. Qualitative analysis confirmed the presence of the stated SARM in about 70% of samples. In 23% of samples, the expected SARM was not detected but a different one instead, and in 1 sample, no SARMs were detected. Other undeclared pharmaceutical substances (tamoxifen, clomifene, testosterone, epimethandienone, tadalafil) were measured in 30% of samples. The copresence of >1 active substance was observed in >60% of samples. Quantitative nuclear magnetic resonance data showed nonuniform content ranging from 30% to 90% of the label claim.

Clinical Implications

The use of SARMs, in the presence of unexpected life-threatening reactions in persons using the products to increase sport performance, should be assessed.

Strengths and Limitations

This investigation involved an integrated approach to study SARM products and related sociologic aspects. The main shortcomings are the limited number of samples and retail websites in the clear web investigated.

Conclusion

SARMs sold online as food supplement–like products represent a health hazard due to the presence of unapproved and undeclared active substances. The presence of contaminants clearly indicates the absence of good manufacturing practices in the production, which increases the health risks.
The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study: feasibility of long-term monitoring with Fitbit smartwatches in central disorders of hypersomnolence and extraction of digital biomarkers in narcolepsy
Authors: Gnarra Oriella , van der Meer Julia , Warncke Jan D , Fregolente Livia G , Wenz Elena , Zub Kseniia , Nwachukwu Uchendu , Zhang Zhongxing , Khatami Ramin , von Manitius Sigrid , Miano Silvia , Acker Jens , Strub Mathias , Riener Robert , Bassetti Claudio L A , Schmidt Markus H
Published: March 2024

The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a multicenter research initiative to identify new biomarkers in central disorders of hypersomnolence (CDH). Whereas narcolepsy type 1 (NT1) is well characterized, other CDH disorders lack precise biomarkers. In SPHYNCS, we utilized Fitbit smartwatches to monitor physical activity, heart rate, and sleep parameters over 1 year. We examined the feasibility of long-term ambulatory monitoring using the wearable device. We then explored digital biomarkers differentiating patients with NT1 from healthy controls (HC). A total of 115 participants received a Fitbit smartwatch. Using a adherence metric to evaluate the usability of the wearable device, we found an overall adherence rate of 80% over 1 year. We calculated daily physical activity, heart rate, and sleep parameters from 2 weeks of greatest adherence to compare NT1 (n = 20) and HC (n = 9) participants. Compared to controls, NT1 patients demonstrated findings consistent with increased sleep fragmentation, including significantly greater wake-after-sleep onset (p = .007) and awakening index (p = .025), as well as standard deviation of time in bed (p = .044). Moreover, NT1 patients exhibited a significantly shorter REM latency (p = .019), and sleep latency (p = .001), as well as a lower peak heart rate (p = .008), heart rate standard deviation (p = .039) and high-intensity activity (p = .009) compared to HC. This ongoing study demonstrates the feasibility of long-term monitoring with wearable technology in patients with CDH and potentially identifies a digital biomarker profile for NT1. While further validation is needed in larger datasets, these data suggest that long-term wearable technology may play a future role in diagnosing and managing narcolepsy.
Albuterol as an adjuvant in acute anticholinesterase pesticide poisoning: a randomized, placebo-controlled clinical trial
Authors: Zein-Elabdeen Samar M M , Hassan Neven A , El-Ebiary Ahmad A , Hafez Amal S A F , Hodeib Aliaa A
Published: March 2024

Acute anticholinesterase pesticide poisoning is a serious clinical problem, particularly in developing countries. Atropine is the most acceptable treatment for acute anticholinesterase poisoning. However, it only stops fluid production. Albuterol is a beta-2 receptor agonist that can increase fluid removal and speed the return of effective oxygen exchange. This study aims to evaluate the safety and efficacy of nebulized albuterol as an adjuvant therapy in patients with acute anticholinesterase poisoning. This stratified block randomized, single-blinded, placebo-controlled, parallel-group clinical trial was conducted between November 2020 and October 2021. It enrolled 80 patients with acute anticholinesterase pesticide poisoning who were admitted to Tanta University Poison Control Center. Patients were allocated into two groups (40 patients each). The strata were based on the severity of poisoning (moderate and severe). Patients in group I received 10 mg of nebulized albuterol. Group II received an equivalent volume of nebulized normal saline. Additionally, standard treatment was provided to both groups. Outcomes included oxygenation, mortality, need for endotracheal intubation and mechanical ventilation, hospital stay duration, time to atropinization, and total doses of atropine and oxime. We found insignificant differences in sociodemographics, exposure characteristics, clinical manifestations, or routine laboratory tests between the studied groups. The median values of oxygen saturation by pulse oximetry were 99% in the albuterol moderate toxicity group and 98% in the control moderate toxicity group. Albuterol significantly improved oxygen saturation in moderate intoxicated patients (P = 0.039). Therefore, nebulized albuterol is a safe drug. Moreover, it may improve oxygenation in acute anticholinesterase pesticide poisoning.
Predicting oncology drug-induced cardiotoxicity with donor-specific iPSC-CMs—a proof-of-concept study with doxorubicin
Authors: Pang Li , Cai Chengzhong , Aggarwal Praful , Wang Dong , Vijay Vikrant , Bagam Prathyusha , Blamer Jacob , Matter Andrea , Turner Amy , Ren Lijun , Papineau Katy , Srinivasasainagendra Vinodh , Tiwari Hemant K , Yang Xi , Schnackenberg Laura , Mattes William , Broeckel Ulrich
Published: March 2024

Many oncology drugs have been found to induce cardiotoxicity in a subset of patients, which significantly limits their clinical use and impedes the benefit of lifesaving anticancer treatments. Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) carry donor-specific genetic information and have been proposed for exploring the interindividual difference in oncology drug-induced cardiotoxicity. Herein, we evaluated the inter- and intraindividual variability of iPSC-CM-related assays and presented a proof of concept to prospectively predict doxorubicin (DOX)-induced cardiotoxicity (DIC) using donor-specific iPSC-CMs. Our findings demonstrated that donor-specific iPSC-CMs exhibited greater line-to-line variability than the intraindividual variability in impedance cytotoxicity and transcriptome assays. The variable and dose-dependent cytotoxic responses of iPSC-CMs resembled those observed in clinical practice and largely replicated the reported mechanisms. By categorizing iPSC-CMs into resistant and sensitive cell lines based on their time- and concentration-related phenotypic responses to DOX, we found that the sensitivity of donor-specific iPSC-CMs to DOX may predict in vivo DIC risk. Furthermore, we identified a differentially expressed gene, DND microRNA-mediated repression inhibitor 1 (DND1), between the DOX-resistant and DOX-sensitive iPSC-CMs. Our results support the utilization of donor-specific iPSC-CMs in assessing interindividual differences in DIC. Further studies will encompass a large panel of donor-specific iPSC-CMs to identify potential novel molecular and genetic biomarkers for predicting DOX and other oncology drug-induced cardiotoxicity.
An investigation of ADAS testing scenarios based on vehicle-to-powered two-wheeler accidents occurring in a county-level district in China
Authors: Wang Honggang , Wang Xinghua , Peng Yong , Lou Xin , Lee Jaeyoung
Published: March 2024

To meet the requirements for high-risk testing scenarios in the safety assessment of advanced driver assistance systems (ADASs), this study selected 239 vehicle-to-powered two-wheeler accidents occurring in Xiangtan County from the China In-depth Mobility Safety Study—Traffic Accident (CIMSS-TA) database. Seven scenario elements were selected from the levels of static road elements, dynamic traffic participants and environment elements. The accident characteristics were obtained through statistical analysis. The results showed that 75.73% of accidents occurred at T-junctions/intersections, and 34.73% were caused by visual obstructions. Six typical vehicle-to-powered two-wheeler crash scenarios were established by cluster analysis, including two straight road scenarios (scenarios 3 and 6), two T-junction scenarios (scenarios 1 and 5) and two intersection scenarios (scenarios 2 and 4). Furthermore, six vehicle-to-powered two-wheeler testing scenarios, which represent the traffic environment characteristics of Chinese county-level districts, were constructed by analysing the vehicle/powered two-wheeler speed, the first collision point of the vehicle, the obstacle type and location, etc. The results showed that the vehicle speed in scenario 4 was higher than that in scenario 2, with average values of 34.32 km/h and 21.99 km/h, respectively. The results of this study provide testing scenarios for the safety assessment of ADASs, and contribute to improving vehicle active safety technology.
Perspectives in precautionary allergen labelling of prepackaged foods after the FAO/WHO consultation
Authors: Fierro Vincenzo , Mazzuca Carmen , Urbani Sara , Dahdah Lamia , Calandrelli Veronica , Valluzzi Rocco Luigi , Giulio Dinardo
Published: March 2024

Purpose of review

The purpose of this review is to provide an overview of the perspectives regarding precautionary allergen labelling (PAL) of prepackaged foods following the consultation conducted by the Food and Agriculture Organization (FAO) and the WHO.

Recent findings

The FAO/WHO consultation provided a comprehensive assessment of the current status and practices of PAL implementation worldwide. One of the key findings highlighted by the Expert Committee was the need for improvement in existing PAL systems. It was noted that many countries lacked uniformity in PAL practices, leading to inconsistencies in labelling and potentially misleading information for consumers. Furthermore, the consultation emphasized the importance of PAL being risk-based, taking into account both the amount and frequency of unintended allergen presence (UAP) in food products.

The FAO/WHO consultation shed light on various perspectives and challenges associated with PAL of prepackaged foods. Key findings emphasized the need for improvement in existing PAL systems, including the adoption of a risk-based approach, standardized regulations, and enhanced transparency. Moving forward, collaborative efforts between regulatory agencies, food manufacturers, and consumer advocacy groups will be essential in developing effective PAL strategies that prioritize consumer safety and well being.
Regular consumption following early introduction of allergenic foods and aggressive treatment of eczema are necessary for preventing the development of food allergy in children
Authors: Sakihara Tetsuhiro
Published: March 2024

Purpose of review

Over the past two decades, food allergy prevention strategies have shifted from ‘delayed introduction’ to ‘no delayed introduction’ to ‘early introduction’ of allergenic foods. This article reviews important research in this field published in the early 2020s to support future strategies for food allergy prevention.

Recent findings

Recent randomized controlled trials (RCTs), systematic reviews, meta-analyses, and real-world studies have reported that early allergenic food introduction, especially peanut and egg, are effective for preventing food allergies. However, there are also reports that food-induced anaphylaxis admission rates in infants are increasing.

Early allergenic food introduction by itself is not sufficient to prevent the development of food allergies. Recent RCTs (SPADE study and COMEET study) have demonstrated that continued regular cow's milk consumption after early introduction is important for preventing the onset of cow's milk allergy. Furthermore, an RCT (PACI study) reported that early and aggressive anti-inflammatory topical therapy for eczema can contribute to the prevention of egg allergy by suppressing percutaneous sensitization. Food allergies may be prevented through a combination of early food introduction, regular consumption, and active eczema treatment. Further research is needed to develop well tolerated, effective, and practical strategies to prevent food allergies.
Variability in Intraoperative Opioid and Nonopioid Utilization During Intracranial Surgery: A Multicenter, Retrospective Cohort Study
Authors: Naik Bhiken I. , Lele Abhijit V. , Sharma Deepak , Akkermans Annemarie , Vlisides Phillip E. , Colquhoun Douglas A. , Domino Karen B. , Tsang Siny , Sun Eric , Dunn Lauren K. ,   the Multicenter Perioperative Outcomes Collaborator Group
Published: March 2024

Background:

Key goals during intracranial surgery are to facilitate rapid emergence and extubation for early neurologic evaluation. Longer-acting opioids are often avoided or administered at subtherapeutic doses due to their perceived risk of sedation and delayed emergence. However, inadequate analgesia and increased postoperative pain are common after intracranial surgery. In this multicenter study, we describe variability in opioid and nonopioid administration patterns in patients undergoing intracranial surgery.

Methods:

This was a multicenter, retrospective observational cohort study using the Multicenter Perioperative Outcomes Group database. Opioid and nonopioid practice patterns in 31,217 cases undergoing intracranial surgery across 11 institutions in the United States are described.

Results:

Across all 11 institutions, total median [interquartile range] oral morphine equivalents, normalized to weight and anesthesia duration was 0.17 (0.08 to 0.3) mg.kg.min-1. There was a 7-fold difference in oral morphine equivalents between the lowest (0.05 [0.02 to 0.13] mg.kg.min-1) and highest (0.36 [0.18 to 0.54] mg.kg.min-1) prescribing institutions. Patients undergoing supratentorial surgery had higher normalized oral morphine equivalents compared with those having infratentorial surgery [0.17 [0.08-0.31] vs. 0.15 [0.07-0.27] mg/kg/min-1; P<0.001); however, this difference is clinically small. Nonopioid analgesics were not administered in 20% to 96.8% of cases across institutions.

Conclusion:

This study found wide variability for both opioid and nonopioid utilization at an institutional level. Future work on practitioner-level opioid and nonopioid use and its impact on outcomes after intracranial surgery should be conducted.
Diagnosis and Management of Cervical Squamous Intraepithelial Lesions in Pregnancy and Postpartum
Authors: Larish Alyssa , Long Margaret E.
Published: March 2024

Perinatal care provides important health care opportunities for many individuals at risk for cervical cancer. Pregnancy does not alter cervical cancer screening regimens. ASCCP risk-based management has a colposcopy threshold of a 4% immediate risk of cervical intraepithelial neoplasia (CIN) 3 or cancer, but the actual risk can be considerably higher based on current and past screening results. Improving cervical cancer outcomes with diagnosis during pregnancy rather than postpartum and facilitating further evaluation and treatment postpartum for lesser lesions are the perinatal management goals. Although colposcopy indications are unchanged in pregnancy, some individuals with lower risk of CIN 2–3 and reliable access to postpartum evaluation may defer colposcopy until after delivery. Cervical intraepithelial neoplasia diagnosed in pregnancy tends to be stable, with frequent regression postpartum, though this is not universal. Colposcopic inspection during pregnancy can be challenging. Although biopsies in pregnancy are subjectively associated with increased bleeding, they do not increase complications. Endocervical curettage and expedited treatment are unacceptable. Treatment of CIN 2–3 in pregnancy is not recommended. Excisional biopsies in pregnancy are reserved for suspicion of malignancy that cannot be confirmed by colposcopic biopsy and when excisional biopsy results would alter oncologic or pregnancy care. Surveillance of high-grade lesions in pregnancy uses human papillomavirus-based testing, cytology, and colposcopy, with biopsy of worsening lesions every 12–24 weeks from diagnosis until postpartum evaluation. Mode of delivery does not definitively affect persistence of CIN postpartum. Postpartum care may involve a full colposcopic evaluation or expedited excisional procedure if indicated.
Midterm treatment results of congenital dislocation of the knee in 14 knees of nine cases
Authors: Tütüncü Mehmed Nuri , Davutluoğlu Ece , Karaismailoğlu Bedri , Kültür Yiğit , Şeker Ali
Published: March 2024

Patients with congenital dislocation of the knee (CDK) should be promptly treated surgically if conservative measures fail. This study aimed to achieve a better understanding of the diagnosis and management of CDK through sharing our experience and contributing to the existing literature. Nine patients with a total of 14 knees were included in the study. All patients except one were initially treated with gentle manipulation and serial casting. Surgery was performed on patients in whom sufficient joint mobility could not be achieved. Active and passive range of motion of the knees and functional outcome were measured. Of the 14 knees, five were classified as first grade, four as second grade and five as third grade. The mean age of the patients was 4.09 months and the follow-up period was 70 months. The initial mean flexion angle (MFA) was 18.2° (0–90) and the mean extension angle (MEA) was 8.2° (0–15). At the final follow-up, the mean MFA was 109.2° (80–140) and MEA was −2.85° (0 to −10). No patient had instability by the final follow-up. The results were classified as excellent (5 knees), good (5 knees) and moderate (4 knees) according to outcome assessment criteria. The functional outcomes were classified as excellent (7 knees), good (3 knees) and fair (4 knees) according to the functional outcome scoring. Treatment of CDK should be started in the first days of life, and if the desired functional outcome cannot be achieved through conservative treatment, surgical treatment should be planned without delay.
How Reliable Is the Measurement of the Lateral Center Edge Angle on Scoliosis Radiographs for Detecting Acetabular Dysplasia?
Authors: Taylor Tristen N. , Duruewuru Anthony T. , Ditzler Matthew G. , Bridges Callie S. , Albar Abeer , Rosenfeld Scott B. , Smith Brian G. , Sher Andrew C. , Kan J. Herman
Published: March 2024

Purpose:

Hip dysplasia reportedly occurs in up to 12% of the general population and may be higher in patients with adolescent idiopathic scoliosis (AIS). When using lateral center edge angle (LCEA) measurements to help identify hip dysplasia, it is uncertain if this measurement can be performed reliably on scoliosis radiographs due to parallax. The purpose of this study is to evaluate the reliability of measuring LCEA on scoliosis radiographs compared with standard pelvis radiographs.

Methods:

This study evaluated 40 hips on 20 patients (mean age 12.5 years ± 3.1; 50% Female) who received PA scoliosis radiographs and AP pelvis radiographs within 1 year of each other. Review was performed by 4 pediatric radiologists (2 general, 2 MSK), 2 pediatric orthopaedic surgeons, and 1 research fellow. Radiographic measurement of the LCEA for each hip was first performed on the scoliosis radiograph. After a minimum of 3 days, the LCEA was measured on a pelvis radiograph of the same individual obtained within 1 year of the scoliosis radiograph. Pearson coefficient was used to measure agreement between scoliosis and pelvis radiograph measurements. Intraclass correlation coefficient (ICC) was used to evaluate intraobserver and interobserver agreement. ICC values <0.5 were classified as poor reliability, 0.5 to 0.75 were classified moderate, 0.75 to 0.90 were classified good, and >0.9 indicated excellent reliability.

Results:

The mean difference between scoliosis and pelvis radiographs was 54 ± 79 days. There was good-to-excellent interobserver agreement on LCEA measurements made between readers on scoliosis radiographs (ICC: 0.94, 95% CI: 0.90-0.96, P<0.001) and pelvis radiographs (ICC: 0.91, 95% CI: 0.83-0.95, P<0.001), and moderate-to-excellent intraobserver agreement for scoliosis radiographs (ICC range: 0.68 to 0.98; P<0.001) and pelvis radiographs (ICC range: 0.62 to 0.96; P<0.001). There was a strong correlation between LCEA measurements made on scoliosis and pelvis radiographs (r
2=0.66, P<0.001), and the intermodality agreement between scoliosis and pelvis radiograph LCEA measurements were moderate to good (ICC range: 0.68 to 0.89, P<0.001).

Conclusions:

Overall, there was good-to-excellent agreement between readers on scoliosis and pelvis radiographs, respectively, and moderate-to-excellent intraobserver agreement between LCEA measurements made on scoliosis radiographs and pelvis radiographs, respectively. LCEA measurements made on scoliosis radiographs strongly correlated to the measurements made on pelvis radiographs, and the intermodality ICC was also considered moderate to good. Dedicated pelvis radiographs may not be necessary during scoliosis workup and follow-up surveillance, thereby decreasing radiation exposure, cost, and improving patient care workflow.

Level of Evidence:

Level IV—diagnostic study.