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Abstract Background The Severity of Alopecia Tool (SALT) is a standardized method for quantifying scalp hair loss in alopecia areata (AA). SALT scores can be used to guide treatment decisions and are widely used as eligibility criteria and endpoints for clinical trials in AA. However, clinicians may be unfamiliar with assessing and envisioning SALT scores in practice. Objectives To aid clinicians in the determination and application of SALT scores in a clinical setting, this manuscript seeks to contextualize SALT scores using patient images from a clinical trial of adults with severe AA. Methods Images from 722 patients enrolled in BRAVE‐AA1, a phase 2/3 study of baricitinib in adults with severe AA (SALT score ≥50; ≥50% scalp hair loss), were obtained at baseline and Weeks 12, 36, and 52 and compiled into a repository. Photographs were selected to represent SALT scores across the full range of disease (SALT scores 0–100) and to demonstrate the progression of SALT scores during the course of treatment. Results Images of six patients depict the range of SALT scores (0–100). Photographs are of male and female patients of different ages (21–69) and races (Asian, Black, White) with varying extent, density, and patterns of hair loss. Images of two additional patients demonstrate the use of SALT to monitor treatment progress, showing distinct patterns and timing of clinical response over 52 weeks of therapy. Conclusions The SALT is widely used in clinical trials for AA, but clinicians may lack familiarity. Presented patient images show SALT scores commonly used as eligibility criteria and endpoints in clinical trials, which may be useful in identifying patients eligible for systemic treatment and in visualizing therapeutic response.

Abstract Background Cow's milk protein allergy (CMPA) remains relatively understudied in Latin America. Methods In this observational study, we enrolled 64 patients with a median age of 3 months, of whom 60% were male. Patients included had a history of IgE‐mediated reactions with IgE sensitization or non‐IgE‐mediated reactions or symptoms following exposure to cow's milk. They underwent skin prick test, ImmunoCAP, fecal calprotectin (FC), and fecal eosinophil‐derived neurotoxin (EDN), in addition to double‐blinded placebo‐controlled oral food challenges (DBPCFC), with clinical evolution and tolerance acquisition observed over 1 year. Results Malnutrition was present in 78.1% of patients, and 87.5% had a family history of atopy, with 51.6% receiving exclusive breastfeeding. Gastrointestinal manifestations were prevalent in 90.6% of patients, followed by dermatological manifestations (10.9%), with only 2 experiencing anaphylaxis. IgE‐mediated CMPA was observed in only six patients. In those with non‐IgE‐mediated CMPA, FC had a median of 284 mg/dL (IQR: 138.5–415.5), while EDN had a median of 508.5 mg/dL (IQR: 160.25–868). One year after diagnosis, median FC significantly decreased (p

Abstract The open‐source programming language ‘R' has become a standard tool in the palaeobiologist's toolkit. Its popularity within the palaeobiological community continues to grow, with published articles increasingly citing the usage of R and R packages. However, there are currently a lack of agreed standards for data preparation and available frameworks to support the implementation of such standards. Consequently, data preparation workflows are often unclear and not reproducible, even when code is provided. Moreover, due to a lack of code accessibility and documentation, palaeobiologists are often forced to ‘reinvent the wheel’ to find solutions to issues already solved by other members of the community. Here, we introduce palaeoverse, a community‐driven R package to aid data preparation and exploration for quantitative palaeobiological research. The package is freely available and has three core principles: (1) streamline data preparation and analyses; (2) enhance code readability; and (3) improve reproducibility of results. To develop these aims, we assessed the analytical needs of the broader palaeobiological community using an online survey, in addition to incorporating our own experiences. In this work, we first report the findings of the survey, which shaped the development of the package. Subsequently, we describe and demonstrate the functionality available in palaeoverse and provide usage examples. Finally, we discuss the resources we have made available for the community and our future plans for the broader Palaeoverse project. palaeoverse is a community‐driven R package for palaeobiology, developed with the intention of bringing palaeobiologists together to establish agreed standards for high‐quality quantitative research. The package provides a user‐friendly platform for preparing data for analysis with well‐documented open‐source code to enhance transparency. The functionality available in palaeoverse improves code reproducibility and accessibility, which is beneficial for both the review process and future research.

Abstract Generalised pustular psoriasis is a rare, unpredictable, and sometimes severe subtype of psoriasis whose treatment is hampered by a lack of consensus and standardised therapeutic guidelines. The recent recognition of the involvement of the innate interleukin (IL)‐1/IL‐36 pathway has allowed the development of new biologic drugs such as Spesolimab. We present the case of a woman with persistent generalised pustular psoriasis (GGP) who, after numerous failures with several systemic and biologic therapies, was treated with Spesolimab and showed a very rapid and sustained response over time.

Objective. Validate the full-PIERS model in predicting adverse maternal outcomes in women with early-onset preeclampsia with severe features in our population. Methods. Retrospective cohort study. We applied the full-PIERS model on 130 women with severe early-onset preeclampsia who were treated at a second-level hospital in Nuevo León, México. We validated the full-PIERS model in its ability to discriminate through the AUROC. Results. The full-PIERS model applied to the data obtained in our study had good discrimination, revealing an AUC of 0.718 (95% CI 0.515–0.921; P=0.017). A cut-off of 7.95 was identified as the cut-off point with the best diagnostic performance, with the highest Youden index, presenting a sensitivity of 54.5% and specificity of 99.2% for the development of complications. Conclusion. The full-PIERS model can predict adverse maternal outcomes in women admitted to our hospital with severe early-onset preeclampsia within 48 hours of admission.

Abstract Inhaled nitric oxide (iNO) is a potent and selective pulmonary vasodilator with a safety concern due to rebound pulmonary hypertension (PH) associated with its withdrawal. We report short‐term pulsed iNO in patients with severe pulmonary arterial hypertension (PAH) and nonoperable chronic thromboembolic PH (nCTEPH). This is a retrospective analysis of 33 patients: 22 with PAH and 11 with nCTEPH. We assessed hemodynamic, echocardiographic, and other noninvasive variables to evaluate safety and efficacy of iNO. We performed an iNO withdrawal test during right heart catheterization and after 3 days of iNO treatment. iNO significantly improved all variables examined in 22 patients with PAH and 11 with nCTEPH. Two patterns of response were observed after sudden iNO withdrawal. Twenty‐nine patients (88%) showed minimal hemodynamic, oxygenation and clinical changes. Four patients (12%) had a reduction in cardiac index ≥20% and PaO2 ≥ 5%, three patients did not show clinical deterioration, and one patient developed hemodynamic collapse that needed iNO administration. This retrospective study suggests that short‐term iNO improves hemodynamics and clinical conditions in some patients with PAH an nCTPEH. However, pulsed iNO withdrawal PH rebound could be a serious concern in these patients. Given the lack of evidence, we do not recommend the use of pulsed iNO in the treatment of patients with chronic PH.

Abstract Aims This study aimed to assess, in patients with cardiogenic shock secondary to unprotected left main coronary artery‐related myocardial infarction (ULMCA‐related AMICS), the incidence and predictors of no recovery of left ventricular function during the admission. Methods and results This was an observational study conducted at two tertiary care centres (2012–20). The main outcome measured was death or requirement for heart transplantation (HT) or left ventricular assist devices (LVAD) during the admission. A total of 70 patients were included. Percutaneous coronary intervention (PCI) was successful in 53/70 patients (75.7%). The combined endpoint of death or requirement of HT or LVAD during the admission occurred in 41/70 patients (58.6%). The highest incidence of the primary endpoint was observed among patients with profound shock and occluded left main coronary artery (LMCA) (20/23, 87%, P

Abstract This paper provides a summary of the work done within the OC6 Phase II project, which was focused on the implementation and verification of an advanced soil–structure interaction model for offshore wind system design and analysis. The soil–structure interaction model comes from the REDWIN project and uses an elastoplastic, macroelement model with kinematic hardening, which captures the stiffness and damping characteristics of offshore wind foundations more accurately than more traditional and simplified soil–structure interaction modeling approaches. Participants in the OC6 project integrated this macroelement capability to coupled aero‐hydro‐servo‐elastic offshore wind turbine modeling tools and verified the implementation by comparing simulation results across the modeling tools for an example monopile design. The simulation results were also compared to more traditional soil–structure interaction modeling approaches like apparent fixity, coupled springs, and distributed springs models. The macroelement approach resulted in smaller overall loading in the system due to both shifts in the system frequencies and increased energy dissipation. No validation work was performed, but the macroelement approach has shown increased accuracy within the REDWIN project, resulting in decreased uncertainty in the design. For the monopile design investigated here, that implies a less conservative and thus more cost‐effective offshore wind design.

In advanced breast cancer, biomarker identification and patient selection using a metastatic tumor biopsy is becoming more necessary. However, the biology of metastasis according to the organ site is largely unknown. Here, we evaluated the expression of 771 genes in 184 metastatic samples across 11 organs, including liver, lung, brain, and bone, and made the following observations. First, all PAM50 molecular intrinsic subtypes were represented across organs and within immunohistochemistry‐based groups. Second, HER2‐low disease was identified across all organ sites, including bone, and HER2 expression significantly correlated with ERBB2 expression. Third, the majority of expression variation was explained by intrinsic subtype and not organ of metastasis. Fourth, subtypes and individual subtype‐related genes/signatures were significantly associated with overall survival. Fifth, we identified 74 genes whose expression was organ‐specific and subtype‐independent. Finally, immune profiles were found more expressed in lung compared to brain or liver metastasis. Our results suggest that relevant tumor biology can be captured in metastatic tissues across a variety of organ sites; however, unique biological features according to organ site were also identified and future studies should explore their implications in diagnostic and therapeutic interventions.

Organotin complexes were prepared through a one-pot reaction with three components by reacting thiosemicarbazide or 4-methyl-3-thiosemicarbazide or 4-phenylthiosemicarbazide, dehydroacetic acid (DHA) and dibutyl, diphenyl, dicyclohexyl, and bis[(trimethylsilyl)methyl]tin(IV) oxides; all complexes were characterized by infrared (IR), ultraviolet-visible (UV-vis), mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy. The 119Sn NMR revealed chemical shifts corresponding to a pentacoordinated environment in solution. The X-ray crystallography of the two complexes evidenced the formation of monomeric complexes with a pentacoordinated geometry around tin via three donor atoms from the ligand, the sulfur of the thiol, the nitrogen of the imine group, and the oxygen of the pyran ring. The geometries of the five-coordinated complexes 3a (Bu2SnL3), 3c (Ph2SnL3), and 3d (Cy2SnL3) acid were intermediate between square pyramidal and trigonal bipyramidal, and complex 1a (Bu2SnL1) adopted a bipyramidal trigonal geometry (BPT). The sulforhodamine B assay assessed the cytotoxicity of organotin(IV) complexes against the MDA-MB-231 and MCF-7 (human mammary adenocarcinoma) cell lines and one normal COS-7 (African green monkey kidney fibroblast). The IC50 values evidenced a significant antiproliferative effect on cancer cells; the complexes were more potent than the positive cisplatin control and the corresponding ligands, dehydroacetic acid thiosemicarbazone (L1), dehydroacetic acid-N(4)-methylthiosemicarbazone (L2), and dehydroacetic acid-N(4)-phenylthiosemicarbazone (L3). The IC50 values also indicated that the organotin(IV) complexes were more cytotoxic against the triple-negative breast cell line MDA-MB-231 than MCF-7, inducing significant morphological alterations. The interactions of organotin(IV) 1c (Ph2SnL1), 1d (Cy2SnL1), and 1e (((CH3)3SiCH2)2SnL1) were evaluated with ss-DNA by fluorescence; intensity changes of the fluorescence were indicative of the displacement of ethidium bromide (EB), confirming the interaction of the organotin(IV) complexes with ss-DNA; the results showed a DNA binding affinity. The thermodynamic parameters obtained through isothermal titration calorimetry showed that the interaction of 1c (Ph2SnL1), with ss-ADN, was exothermic. Molecular docking studies also demonstrated that the organotin(IV) complexes were intercalated in DNA by conventional hydrogen bonds, carbon-hydrogen bonds, and π-alkyl interactions. These complexes furthermore showed a greater affinity towards DNA than cisplatin.

Abstract Fine‐scale movement patterns are driven by both biotic (hunting, physiological needs) and abiotic (environmental conditions) factors. The energy balance governs all movement‐related strategic decisions. Marine environments can be better understood by considering the vertical component. From 24 acoustic trackings of 10 white sharks in Guadalupe Island, this study linked, for the first time, horizontal and vertical movement data and inferred six different behavioral states along with movement states, through the use of hidden Markov models, which allowed to draw a comprehensive picture of white shark behavior. Traveling was the most frequent state of behavior for white sharks, carried out mainly at night and twilight. In contrast, area‐restricted searching was the least used, occurring primarily in daylight hours. Time of day, distance to shore, total shark length, and, to a lesser extent, tide phase affected behavioral states. Chumming activity reversed, in the short term and in a nonpermanent way, the behavioral pattern to a general diel vertical pattern.

Abstract The trajectory linearisation control of a non‐linear system using only output information and considering the presence of matched and unmatched uncertainties/perturbations is presented. A continuous sliding mode controller is used to achieve finite‐time tracking of a given continuous time‐varying reference and assuring theoretically exact reconstruction of the matched and unmatched uncertainties/perturbations. The states are reconstructed theoretically exactly in finite time using a linear time‐varying observer based on a high‐order sliding mode framework. The proposed approach is validated using MATLAB simulations.

Background Patients with acute ischemic stroke due to large vessel occlusion may present with concomitant carotid dissections that make the technical approach for their treatment challenging. The purpose of this study was to determine the safety and feasibility of flow diverter (FD) stents to treat carotid artery dissections in tandem lesions of acute ischemic stroke patients during mechanical thrombectomy. Methods A retrospective review of all patients in which a carotid artery dissection was treated with an FD during endovascular treatment of acute ischemic stroke between 2018 and 2020 was conducted in 5 high‐volume Comprehensive Stroke Centers. Patient clinical and angiographical characteristics, postoperative outcome, and follow‐up were recorded. Results A total of 12 patients (mean age: 54.18±14.74 years, median Alberta Stroke Program Early CT Score: 10 [interquartile range 9–10]) were included. Successful FD stenting with immediate patency of the dissected segments and successful intracranial recanalization modified thrombolysis in cerebral infarction score 2b‐3 after thrombectomy was achieved in all patients. A good outcome (modified Rankin scale 0–2 at 90 days) was achieved in 66% (8/12) of patients. In 25% (3/12) of patients, an additional self‐expanding carotid stent was used to anchor the FD proximally at the carotid bulb level. Complications included 1 symptomatic intracranial hemorrhage after procedure (24–48 hours) and 2 in‐stent stenoses at follow‐up. Conclusions In this small case series, the treatment of carotid artery dissection with FD stents was safe and technically feasible during mechanical thrombectomy of acute ischemic stroke patients with tandem lesions and resulted in a high rate of good clinical outcome. These results may provide the basis for designing larger prospective studies to assess the efficacy and safety of FD stents in selected patients with carotid tandem lesions.

Introduction. Pediatric liver transplant recipients have demonstrated excellent long-term survival. The purpose of this analysis is to investigate factors associated with 20-year survival to identify areas for improvement in patient care. Methods. Kaplan–Meier with log-rank test as well as univariate and multivariate logistic regression methods were used to retrospectively analyze 4,312 liver transplant recipients under the age of 18 between September 30, 1987 and March 9, 1998. Our primary endpoint was 20-year survival among one-year survival. Results. Logistic regression analysis identified recipient age as a significant risk factor, with recipients below 5 years old having a higher 20-year survival rate (p

Transient receptor potential melastatin‐4 channel (TRPM4) dysregulation contributes to heart conditions, immune diseases, and cervical and prostate cancer. Up to now, the involvement of TRPM4 in colorectal cancer (CRC) pathophysiology remains unknown. Here, we investigated tumor tissue microarrays from 379 CRC patients and analyzed TRPM4 protein expression, tumor characteristics, and clinical outcome. High TRPM4 protein expression was associated with unfavorable tumor features characteristic for epithelial–mesenchymal transition and infiltrative growth patterns, that is, a high number of tumor buds and a low percentage in tumor border configuration. Compared to CRC cells representing early cancer stages, TRPM4 protein expression was the highest in cells representing late‐stage metastatic cancer. Investigation of CRC cell line HCT116 and five CRISPR/cas9 TRPM4 knockout clones demonstrated that TRPM4 exhibited large Na+ current densities (~ 60 pA/pF). In addition, CRISPR/cas9 TRPM4 knockout clones showed a tendency toward decreased migration and invasion, cell viability, and proliferation and exhibited a shift in cell cycle when compared to HCT116. Stable overexpression of TRPM4 (TRPM4 wild‐type) in two CRISPR/cas9 TRPM4 knockout clones rescued the decrease in cell viability and cell cycle shift. Stable overexpression of a nonconducting, dominant‐negative TRPM4 mutant (TRPM4 D894A) did not rescue the decrease in viability or cell cycle shift. Taken together, these findings pointed to TRPM4 ion channel conductivity as the underlying mechanism for decreased viability and cell cycle shift in the TRPM4 knockout clones. Together with previous findings, our present data suggest that TRPM4 plays a versatile role in cancer cell proliferation, cell cycle, and invasion.

Background Fetal posterior cerebral artery (FPCA) occlusion is a rare but potentially disabling cause of stroke. While endovascular treatment is established for acute large vessel occlusion stroke, FPCA occlusions were excluded from acute ischemic stroke trials. We aim to report the feasibility, safety, and outcome of mechanical thrombectomy in acute FPCA occlusions. Methods We performed a multicenter retrospective review of consecutive patients who underwent mechanical thrombectomy of acute FPCA occlusion. Primary FPCA occlusion was defined as an occlusion that was identified on the pre‐procedure computed tomography angiography or baseline angiogram whereas a secondary FPCA occlusion was defined as an occlusion that occurred secondary to embolization to a new territory after recanalization of a different large vessel occlusion. Demographics, clinical presentation, imaging findings, endovascular treatment, and outcome were reviewed. Results There were 25 patients with acute FPCA occlusion who underwent mechanical thrombectomy, distributed across 14 centers. Median National Institutes of Health Stroke Scale on presentation was 16. There were 76% (19/25) of patients who presented with primary FPCA occlusion and 24% (6/25) of patients who had a secondary FPCA occlusion. The configuration of the FPCA was full in 64% patients and partial or “fetal‐type” in 36% of patients. FPCA occlusion was missed on initial computed tomography angiography in 21% of patients with primary FPCA occlusion (4/19). The site of occlusion was posterior communicating artery in 52%, P2 segment in 40% and P3 in 8% of patients. Thrombolysis in cerebral infarction 2b/3 reperfusion was achieved in 96% of FPCA patients. There were no intraprocedural complications. At 90 days, 48% (12/25) were functionally independent as defined by modified Rankin scale≤2. Conclusions Endovascular treatment of acute FPCA occlusion is safe and technically feasible. A high index of suspicion is important to detect occlusion of the FPCA in patients presenting with anterior circulation stroke syndrome and patent anterior circulation. Novelty and significance This is the first multicenter study showing that thrombectomy of FPCA occlusion is feasible and safe.

Social cognition (SC) deficits have been linked to Parkinson’s disease (PD) but have been less well researched than general cognitive processes, especially in early-onset PD (EOPD), despite this population often having greater social and family demands. Most studies focus on recognition of facial emotion, theory of mind (ToM), and decision-making domains, with limited research reporting on social reasoning. The main objective of this work was to compare SC ability across four domains: emotional processing, social reasoning, ToM, and decision-making between patients with EOPD and healthy controls. Twenty-five nondemented patients with EOPD and 25 controls matched for sex, age, and educational level were enrolled. A battery that included six SC tests was administered to all study participants; a decision-making scale was completed by participants’ partners. Statistically significant differences were found between patients with EOPD and controls in all subtests across the four SC domains studied. The EOPD group demonstrated worse performance on all tasks, with large effect sizes. Differences remained significant after adjusting for Montreal Cognitive Assessment (MoCA) test scores for all SC subtests except the decision-making scale and the Iowa gambling task. No significant correlations between SC and other clinical PD variables were found. Our study shows that patients with EOPD perform significantly below controls in multiple SC domains affecting recognition of facial emotion, social reasoning, ToM, and decision-making. Only decision-making seems to be mediated by overall cognitive ability. The confounding or contributing effect of other clinical PD variables should be studied further.

The power converters are widely used in several industrial applications where it is necessary to obtain from a fixed voltage another one higher or lower than the original. In this paper, we focus on the DC-DC (direct current) boost converters, where to guarantee the desired voltage, an internal current tracking loop is usually used. However, this tracking cannot be assured in the presence of unknown load changes and external perturbations when traditional controller strategies are implemented. In this paper, an advanced control strategy is proposed to ensure the current tracking using a saturated super-twisting controller on the power converter. The finite-time current tracking of a DC-DC boost converter is assured in the presence of bounded Lipschitz perturbations composed by unknown load changes and exogenous signals. The proposed approach generates a continuous bounded control signal applied to the converter by using a sigma-delta modulator ΣΔM. The controller gains are tuned to obtain finite-time stabilization of the tracking error, while the control signal remains bounded. To illustrate the effectiveness of the proposed results, the controller is applied to a physical boost converter using the hardware implemented ΣΔM and an STM32 Discovery development card. Besides, the controller is compared with a first-order sliding mode controller showing that for small sample times, the energy of the error signal is reduced.