bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure‐based pharmacophore modeling, virtual screening approaches to identifying the potent hepatitis C viral protease and polymerase novel inhibitors
Authors: Venkatesan Arthi , Dhanabalan Anantha Krishnan , Rajendran Selvakumar , Shanmugasundharam Shyamala Gowri , Gunasekaran Krishnasamy , Febin Prabhu Dass J.
Published: June 2022

Hepatitis C is an infectious disease that leads to acute and chronic liver illnesses. Currently, there are no effective vaccines against this deadly virus. Direct acting antiviral (DAA) drugs are given in the combination with ribavirin and pegylated interferon which lead to adverse effects. Through in silico analysis, the structure‐based docking study was performed against NS3/4A protease and NS5B polymerase proteins of HCV. In the current study, multiple e‐pharmacophore‐based virtual screening methods such as HTVS, SP, and XP were carried out to screen natural compounds and enamine databases. Our result outcomes revealed that CID AE‐848/13196185 and CID AE‐848/36959205 compounds show good binding interactions with protease protein. In addition, CID 15081408 and CID 173568 show better binding interactions with the polymerase protein. Further to validate the docking results, we performed molecular dynamics simulation for the top hit compounds bound with protease and polymerase proteins to illustrate conformational differences in the stability compared with the active site of the cocrystal inhibitor. Thus, the current study emphasizes these compounds could be an effective drug to treat HCV.
The relationship between posttherapeutic Cognitive Behavior Therapy skills usage and follow‐up outcomes of internet‐delivered Cognitive Behavior Therapy
Authors: Eilert Nora , Wogan Rebecca , Adegoke Adedeji , Earley Caroline , Duffy Daniel , Enrique Angel , Palacios Jorge , Timulak Ladislav , Richards Derek
Published: June 2022

Background

Clients independently applying Cognitive Behavior Therapy (CBT) skills is an important outcome of CBT‐based treatments. The relationship between posttherapeutic CBT skills usage and clinical outcomes remains under‐researched—especially after internet‐delivered CBT (iCBT).

Objective

Explore contemporaneous and lagged effects of posttherapeutic CBT skills usage frequency on iCBT follow‐up outcomes.

Method

Nested within a randomized controlled trial, 241 participants received 8‐week supported iCBT for anxiety and/or depression, completing measures of anxiety, depression, functional impairment, and CBT skills usage frequency at 3‐, 6‐, 9‐, and 12‐month follow‐up. Cross‐lagged panel models evaluated primary aims.

Results

While analyses support a contemporaneous relationship between anxiety, depression, functional impairment, and CBT skills usage frequency, no consistent lagged effects were observed.

Conclusion

Findings align with qualitative research but the role of CBT skills usage in the maintenance of iCBT effects remains unclear. Innovative research modeling temporal and possibly circular relationships between CBT skill usage and clinical outcomes is needed to inform iCBT optimization.
OMICRON: Virology, immunopathogenesis, and laboratory diagnosis
Authors: Bazargan Mahsa , Elahi Reza , Esmaeilzadeh Abdolreza
Published: June 2022

Since its emersion, coronavirus disease 2019 (COVID‐19) has been a significant global dilemma. Several mutations in the severe acute respiratory virus (SARS‐Co‐2) genome has given rise to different variants with various levels of transmissibility, severity and mortality. Up until November 2021, the variants of concern declared by the World Health Organization were Alpha, Beta, Delta and Gamma. Since then, a novel variant named Omicron (B.1.1.529) has been developed. BA.1, BA.1.1, BA.2 and BA.3 are four known subvariants of Omicron. The Omicron variant involves new mutations in its spike protein, most of which are in its receptor binding site, and increase its transmissibility and decrease its antibody and vaccine response. Understanding the virology and mutations of Omicron is necessary for developing diagnostic and therapeutic methods. Moreover, important issues, such as the risk of re‐infection, the response to different kinds of vaccines, the need for a booster vaccine dose and the increased risk of Omicron infection in pediatrics, need to be addressed. In this article, we provide an overview of the biological and immunopathological properties of Omicron and its subvariants, its clinical signs and symptoms, Omicron and pediatrics, vaccines against Omicron, re‐infection with Omicron, diagnostic approaches and specific challenges of Omicron in the successful control and management of the rapid global spread of this variant.
A novel strategy to dissect multifaceted macrophage function in human diseases
Authors: Karlinsey Keaton , Qu Lili , Matz Alyssa J , Zhou Beiyan
Published: June 2022

Macrophages are widely distributed immune cells that play central roles in a variety of physiologic and pathologic processes, including obesity and cardiovascular disease (CVD). They are highly plastic cells that execute diverse functions according to a combination of signaling and environmental cues. While macrophages have traditionally been understood to polarize to either proinflammatory M1-like or anti-inflammatory M2-like states, evidence has shown that they exist in a spectrum of states between those 2 phenotypic extremes. In obesity-related disease, M1-like macrophages exacerbate inflammation and promote insulin resistance, while M2-like macrophages reduce inflammation, promoting insulin sensitivity. However, polarization markers are expressed inconsistently in adipose tissue macrophages, and they additionally exhibit phenotypes differing from the M1/M2 paradigm. In atherosclerotic CVD, activated plaque macrophages can also exist in a range of proinflammatory or anti-inflammatory states. Some of these macrophages scavenge lipids, developing into heterogeneous foam cell populations. To better characterize the many actions of macrophages in human disease, we have designed a novel set of computational tools: MacSpectrum and AtheroSpectrum. These tools provide information on the inflammatory polarization status, differentiation, and foaming of macrophages in both human and mouse samples, allowing for better characterization of macrophage subpopulations based on their function. Using these tools, we identified disease-relevant cell states in obesity and CVD, including the novel concept that macrophage-derived foam cell formation can follow homeostatic noninflammatory or pathogenic inflammatory foaming programs.
Glycogen storage disease type 1a in the Ohio Amish
Authors: Scott Ethan M. , Wenger Olivia K. , Robinson Elizabeth , Colling Kristina , Brown Miraides F. , Hershberger Jennifer , Radhakrishnan Kadakkal
Published: June 2022

Glycogen storage disease type 1a (GSD1a) is an inborn error of glucose metabolism characterized by fasting hypoglycemia, hepatomegaly, and growth failure. Late complications include nephropathy and hepatic adenomas. We conducted a retrospective observational study on a cohort of Amish patients with GSD1a. A total of 15 patients cared for at a single center, with a median age of 9.9 years (range 0.25–24 years) were included. All patients shared the same founder variant in GCPC c.1039 C > T. The phenotype of this cohort demonstrated good metabolic control with median cohort triglyceride level slightly above normal, no need for continuous overnight feeds, and a higher quality of life compared to a previous GSD cohort. The most frequent complications were oral aversion, gross motor delay, and renal hyperfiltration. We discuss our unique care delivery at a single center that cares for Amish patients with inherited disorders.
Late Pleistocene and Holocene palaeoecological reconstruction of Lake Texcoco (Basin of Mexico) based on its ostracod record
Authors: Chávez‐Lara C.M. , Lozano‐García S. , Ortega‐Guerrero B. , Caballero‐Miranda M.
Published: June 2022

We present a palaeohydrological reconstruction of Lake Texcoco over the last 32.7 cal ka based on ostracod records consisting of two species, Candona patzcuaro and Limnocytherina axalapasco. Overall, the presence of these species suggests that Lake Texcoco was highly saline and experienced occasional desiccation periods. Moreover, this work helps improve our knowledge of L. axalapasco, an endemic species of central Mexico; their eggs could remain dormant‐resting to survive long dry periods. Four ostracod zones reflect the main environmental changes that occurred during the Late Pleistocene and Holocene. From 32.7 to 30 cal ka bp (Zone 4), Lake Texcoco's water levels were stable and alkaline with saline conditions. Zone 3, representing the period from 30 to 18 cal ka bp, includes a period of enhanced precipitation (greatest abundance of C. patzcuaro) from 30 to 26 cal ka bp. From 26 to 18 cal ka bp, an abundance of L. axalapasco reflects shallower and more saline conditions. The Last Glacial Maximum was characterised by cold and humid conditions with enhanced runoff, especially at 25.3, 21.9, and 20.7 cal ka bp. Zone 2 (18–7 cal ka bp) represents the driest period on record. Finally, shallow and saline lake conditions have prevailed over the last 7 cal ka (Zone 1).
Overview about Raman spectroscopy of types of olivine group minerals: A brief review
Authors: do Nascimento‐Dias Bruno Leonardo
Published: June 2022

The main idea of this work is to develop a brief synthesized review of the spectra of the members of the olivine group (forsterite, fayalite, Co‐olivine, and Ni‐olivine). In particular, the objective is to descriptively evaluate the different κ1 and κ2 values from the spectral bands of each mineral. The results gathered from the documentary survey of several published articles, it was possible to notice a substantial difference between the κ1 and κ2 values of forsterite and the other members. On the other hand, the difference between the values of κ1 and κ2 among the other members is almost imperceptible (fayalite, Ni‐olivine, and Co‐olivine). Thus, the probable main difference between all fayalite and other members (Co‐ and Ni‐olivine) can be seen in lower wavenumbers between 200 and 300 cm−1. In conclusion, if the objective is just to distinguish olivine, the doublet band is a good parameter to be used, but if you want to detail about which mineral of the olivine group was analyzed, the lower wavenumbers probably are the best choices.
Albumin‐bilirubin score is superior to platelet‐albumin‐bilirubin score and model for end‐state liver disease sodium for predicting posthepatectomy liver failure
Authors: Wong William G. , Perez Holguin Rolfy A. , Tarren Anna Y. , Shen Chan , Vining Charles , Peng June S. , Dixon Matthew E.
Published: June 2022

Background

Risk stratification for patients undergoing hepatectomy can be attempted using established models. This study compares the platelet‐albumin‐bilirubin (PALBI) score with albumin‐bilirubin (ALBI) and model for end‐stage liver disease sodium (MELD‐Na) for predicting posthepatectomy liver failure (PHLF) and 30‐day mortality.

Methods

The 2014–2018 NSQIP database was queried for patients who underwent elective hepatectomy. Multivariable logistic regressions assessed associations of posthepatectomy outcomes with patient and clinical characteristics. Predictive accuracy of the grading systems was evaluated using receiver operator characteristic (ROC) curves and calculating area under the curve (AUC).

Results

Severe PHLF (Grade B/C) and mortality were present in 2.58% (N = 369) and 1.2% (N = 171) of patients who underwent hepatectomy (N = 13 925), respectively. ALBI Grade 2/3 had a stronger association with severe PHLF (odds ratio [OR] = 1.62, p < 0.01) and mortality (OR = 2.06, p < 0.005) than PALBI Grade 2/3 (OR = 1.14, p = 0.43 for PHLF and OR = 2.01, p < 0.005 for mortality) or MELD‐Na ≥10 (OR = 1.29, p = 0.25 for PHLF and OR = 1.84, p < 0.03). ALBI had a higher AUC (0.671) than PALBI (0.625) and MELD‐Na (0.627) for predicting severe PHLF. ALBI had a higher AUC (0.695) than PALBI (0.642) for predicting 30‐day mortality.

Conclusions

ALBI was a more accurate predictor of severe PHLF and 30‐day mortality than MELD‐Na and PALBI for patients who underwent hepatectomy.
Prognostic significance of preoperative and postoperative CA 19‐9 normalization in pancreatic adenocarcinoma treated with neoadjuvant therapy or surgery first
Authors: DiPeri Timothy P. , Newhook Timothy E. , Prakash Laura R. , Ikoma Naruhiko , Maxwell Jessica E. , Kim Michael P. , Lee Jeffrey E. , Katz Matthew H. G. , Tzeng Ching‐Wei D.
Published: June 2022

Background

Normal(ization) of serum carbohydrate 19‐9 (CA19‐9) before/after surgery has not been compared in patients with pancreatic adenocarcinoma (PDAC) treated with neoadjuvant therapy (NT) versus surgery‐first (SF).

Methods

Characteristics for patients with PDAC who underwent resection from July 2011 to October 2018 were collected. Patients with pre‐/postoperative CA19‐9, bilirubin <2 mg/dL, and initial CA19‐9 > 1 U/ml were included. Overall survival (OS) and recurrence‐free survival (RFS) were compared by pre‐/postoperative CA19‐9.

Results

In patients receiving NT, normal pre/postoperative CA19‐9 (“NTnl/nl”) was associated with median RFS and OS (26 and 77mo), followed by those who normalized after surgery (“NTabnl/nl” 16 and 44mo). For SF patients, normal pre‐/postoperative CA19‐9 (“SFnl/nl”) was associated with median RFS and OS (115 and not estimable mo), followed by those who normalized after resection (“SFabnl/nl” 18 and 49mo). Groups “NTabnl/abnl” and “SFabnl/abnl” with elevated CA19‐9 both before and after resection had the worst median RFS and OS durations.

Conclusions

While a normal(ized) postoperative CA19‐9 may result in similar survival as preoperative normal(ization), postoperative normalization failed to occur in nearly 30% of SF patients. NT should be considered in patients presenting with elevated CA19‐9. If considering SF, ideal patients may include those with normal CA19‐9 at presentation.
Ultrasound of the Hook of Hamate Region: Pictorial Review
Authors: Nischal Neha , Bianchi Stefano
Published: June 2022

The hook of hamate is a complex anatomical region with many small but important structures. A sound knowledge of anatomy along with a systematic ultrasound technique can help delineate a variety of disorders. In this pictorial review, we discuss the ultrasound anatomy and the possible pathologies that can be encountered in this region.
Dynamic Urea Bond‐Mediated Polymerization for Solvent‐Free Low‐Ð Linear Polyurethanes of Controlled Molar Mass: Hypothesis of Diffusion Control
Authors: Polo Fonseca Lucas
Published: June 2022

Dynamic urea bond‐mediated polymerization (DUBMP) has been employed for the synthesis of linear, branched, telechelic, and random‐block polyurethanes (PUs) with low molar‐mass dispersity relative to conventionally synthesized PUs (Đ < 1.5). However, the reason for the improved control of the molar mass and reduction in dispersity, promoted by DUBMP, has not been explained. In this paper, the DUBMP synthesis of linear PU based on low‐molar‐mass poly(ethylene glycol) (PEG) and isophorone diisocyanate is studied comprehensively. The lower viscosity of the PEG‐based PU allows DUBMP to reach high conversions (≈0.97) for the first time, while molar mass and Đ vary substantially with reaction conditions, despite yielding similar/equal conversion values. Both molar mass and Đ increase with an increase in reaction temperature, or with a reduction of the amine/isocyanate molar ratio. Therefore, evidence suggests that DUBMP provides diffusion control due to the lower mobility of the longer chains associated with an isocyanate‐deactivator‐rich environment. An increase in the reaction temperature, and/or a decrease in the amine/isocyanate molar ratio, reduces the diffusion control, leading to higher Đ values and molar mass. Tuning of the reaction conditions allows obtaining PU of controlled molar mass (11 kDa ≤ Mw ≤ 42 kDa) and 1.3 < Đ < 1.75.
Green Polymer Electrolytes Based on Polycaprolactones for Solid‐State High‐Voltage Lithium Metal Batteries
Authors: Chen Yi‐Hsuan , Hsieh Yi‐Chen , Liu Kun Ling , Wichmann Lennart , Thienenkamp Johannes Helmut , Choudhary Aditya , Bedrov Dmitry , Winter Martin , Brunklaus Gunther
Published: June 2022

Solid polymer electrolytes (SPEs) have attracted considerable attention for high energy solid‐state lithium metal batteries (LMBs). In this work, potentially ecofriendly, solid‐state poly(ε‐caprolactone) (PCL)‐based star polymer electrolytes with cross‐linked structures (xBt‐PCL) are introduced that robustly cycle against LiNi0.6Mn0.2Co0.2O2 (NMC622) composite cathodes, affording long‐term stability even at higher current densities. Their superior features allow for sufficient suppression of dendritic lithium deposits, as monitored by 7Li solid‐state NMR. Advantageous electrolyte|electrode interfacial properties derived from cathode impregnation with 1.5 wt% PCL enable decent cell performance until up to 500 cycles at rates of 1C (60 °C), illustrating the high potential of PCL‐based SPEs for application in high‐voltage LMBs.
Transcriptional and metabolic remodeling in clear cell renal cell carcinoma caused by ATF4 activation and the integrated stress response (ISR)
Authors: van der Mijn Johannes C. , Chen Qiuying , Laursen Kristian B. , Khani Francesca , Wang Xiaofei , Dorsaint Princesca , Sboner Andrea , Gross Steven S. , Nanus David M. , Gudas Lorraine J.
Published: June 2022

Research has shown extensive metabolic remodeling in clear cell renal cell carcinoma (ccRCC), with increased glutathione (GSH) levels. We hypothesized that activating transcription factor‐4 (ATF4) and the integrated stress response (ISR) induce a metabolic shift, including increased GSH accumulation, and that Vitamin A deficiency (VAD), found in ccRCCs, can also activate ATF4 signaling in the kidney. To determine the role of ATF4, we used publicly available RNA sequencing (RNA‐seq) data sets from The Cancer Genomics Atlas. Subsequently, we performed RNA‐seq and liquid chromatography–mass spectrometry‐based metabolomics analysis of the murine TRAnsgenic Cancer of the Kidney (TRACK) model for early‐stage ccRCC. To validate our findings, we generated RCC4 cell lines with ATF4 gene edits (ATF4‐knockout [KO]) and subjected these cells to metabolic isotope tracing. Analysis of variance, the two‐sided Student's t test, and gene set enrichment analysis were used (p < 0.05) to determine statistical significance. Here we show that most human ccRCC tumors exhibit activation of the transcription factor ATF4. Activation of ATF4 is concomitant with enrichment of the ATF4 gene set and elevated expression of ATF4 target genes ASNS, ALDH1L2, MTHFD2, DDIT3 (CHOP), DDIT4, TRIB3, EIF4EBP1, SLC7A11, and PPP1R15A (GADD34). Transcript profiling and metabolomics analyses show that activated hypoxia‐inducible factor‐1α (HIF1α) signaling in our TRACK ccRCC murine model also induces an ATF4‐mediated ISR. Notably, both normoxic HIF1α signaling in TRACK kidneys and VAD in wild‐type kidneys diminish amino acid levels, increase ASNS, TRIB3, and MTHFD2 messenger RNA levels, and increase levels of lipids and GSH. By metabolic isotope tracing in human RCC4 kidney cancer parental and ATF4 gene‐edited (ATF4‐KO) cell lines, we show that ATF4 increases GSH accumulation in part via activation of the mitochondrial one‐carbon metabolism pathway. Our results demonstrate for the first time that activation of ATF4 enhances GSH accumulation, increases purine and pyrimidine biosynthesis, and contributes to transcriptional and metabolic remodeling in ccRCC. Moreover, constitutive HIF1α expressed only in murine kidney proximal tubules activates ATF4, leading to the metabolic changes associated with the ISR. Our data indicate that HIF1α can promote ccRCC via ATF4 activation. Moreover, lack of Vitamin A in the kidney recapitulates aspects of the ISR.
Predicting the outcome of radiotherapy in brain metastasis by integrating the clinical and MRI‐based deep learning features
Authors: Jalalifar Seyed Ali , Soliman Hany , Sahgal Arjun , Sadeghi‐Naini Ali
Published: June 2022

Background

A considerable proportion of metastatic brain tumors progress locally despite stereotactic radiation treatment, and it can take months before such local progression is evident on follow‐up imaging. Prediction of radiotherapy outcome in terms of tumor local failure is crucial for these patients and can facilitate treatment adjustments or allow for early salvage therapies.

Purpose

In this work, a novel deep learning architecture is introduced to predict the outcome of local control/failure in brain metastasis treated with stereotactic radiation therapy using treatment‐planning magnetic resonance imaging (MRI) and standard clinical attributes.

Methods

At the core of the proposed architecture is an InceptionResentV2 network to extract distinct features from each MRI slice for local outcome prediction. A recurrent or transformer network is integrated into the architecture to incorporate spatial dependencies between MRI slices into the predictive modeling. A visualization method based on prediction difference analysis is coupled with the deep learning model to illustrate how different regions of each lesion on MRI contribute to the model's prediction. The model was trained and optimized using the data acquired from 99 patients (116 lesions) and evaluated on an independent test set of 25 patients (40 lesions).

Results

The results demonstrate the promising potential of the MRI deep learning features for outcome prediction, outperforming standard clinical variables. The prediction model with only clinical variables demonstrated an area under the receiver operating characteristic curve (AUC) of 0.68. The MRI deep learning models resulted in AUCs in the range of 0.72 to 0.83 depending on the mechanism to integrate information from MRI slices of each lesion. The best prediction performance (AUC = 0.86) was associated with the model that combined the MRI deep learning features with clinical variables and incorporated the inter‐slice dependencies using a long short‐term memory recurrent network. The visualization results highlighted the importance of tumor/lesion margins in local outcome prediction for brain metastasis.

Conclusions

The promising results of this study show the possibility of early prediction of radiotherapy outcome for brain metastasis via deep learning of MRI and clinical attributes at pre‐treatment and encourage future studies on larger groups of patients treated with other radiotherapy modalities.
Development and applicability of a dignity‐centred palliative care programme for people with idiopathic pulmonary fibrosis: A qualitative‐driven mixed methods study
Authors: Igai Yasuko , Porter Sarah E.
Published: June 2022

Aims

This study evaluated the acceptability of a dignity‐centred palliative care programme for people with idiopathic pulmonary fibrosis by converging perceptions of living with idiopathic pulmonary fibrosis qualitative data and quantitative data.

Design

The qualitative‐driven mixed methods research addressed the study aim by using a convergent design. This single arm, non‐randomized study used purposive sampling.

Methods

Interviews with 12 stable outpatients with IPF provided qualitative data. Their quantitative data were from six scales: self‐esteem, health‐related quality of life, anxiety, depression, dyspnoea, cough and programme satisfaction. Intervention was three educational modules: symptom management, enhancing daily activities and life reviews.

Results

Semi‐structured interviews yielded eight categories. Self‐esteem was not statistically significantly changed. Dyspnoea symptoms improved significantly. Participants (n = 9) holding positive attitudes for living with idiopathic pulmonary fibrosis, had improved lifestyle behaviour and improved or maintained self‐esteem. The meta‐inference regarding idiopathic pulmonary fibrosis perceptions were related to changes in self‐esteem.
EEGcorrelates of quality of life and associations with seizure without awareness and depression in patients with epilepsy
Authors: Azuma Hideki , Akechi Tatsuo
Published: June 2022

Aims

Quality of life (QOL) is an important issue for not only patients with epilepsy but also physicians. Depression has a large impact on QOL. Nonlinear electroencephalogram (EEG) analysis using machine learning (ML) has the potential to improve the accuracy of the diagnosis of epilepsy. Therefore, in this study, we examined EEG nonlinearity, EEG correlates of QOL in patients with epilepsy, and the accuracy of EEG for the interval from seizure without awareness (SA–) and for depression, using ML.

Methods

The Side Effects and Life Satisfaction (SEALS) inventory was used to assess QOL, and the Neurological Disorders Depression Inventory for Epilepsy (NDDI‐E) was used as a screening tool for depression on the date of the EEG recording. EEG with wavelet denoising (WD), the Savitzky–Golay filter, and non‐denoising were created in combination with low‐ and high‐pass filters. These EEG sets were adopted for phase space reconstruction methods. Using a generalized linear mixed‐effects model for SEALS, sample entropy as a measurement of regularity, SA–, seizure with awareness, and depression were examined.

Results

WD and non‐denoising EEG sets in the bilateral posterior temporal‐occipital, centro‐parietal, parieto‐occipital, and Fz–Cz of the 10–20 method were associated with SEALS and demonstrated nonlinearity, and the moderate effects of classification for the interval elapsed from SA– and for depression. When the intervals from SA– were added, the effects of the EEG classification for depression increased.

Conclusion

These findings suggest that EEG regions associated with QOL showing nonlinearity are useful for classifying SA– and depression.
Puberty in pre‐Roman times: A bioarchaeological study of Etruscan‐Samnite adolescents from Pontecagnano (southern Italy)
Authors: Bareggi Alessia , Pellegrino Carmine , Giuffra Valentina , Riccomi Giulia
Published: June 2022

Objectives

Puberty is a crucial part of life, representing the biological transition from childhood to adulthood. With the aim of expanding current knowledge of pubertal development and the life course in past populations, this study provides the first investigation of puberty in pre‐Roman Italy.

Materials and methods

Nine skeletal and dental puberty indicators were assessed in a sample of 84 Etruscan and Samnite individuals (8.0–23.9 years) from Pontecagnano (southern Italy, seventh–fourth centuries BC) to garner insights into the timing and duration of different pubertal stages.

Results

Adolescents from Pontecagnano entered puberty at 10–12 years and completed pubertal development at approximately 20–21 years. Menarche occurred between 14 and 17 years. Remarkable variability in pubertal timing and an overall prolonged pubertal tempo were observed. Unexpectedly, females completed puberty at the same age as males.

Discussion

The onset and completion of puberty in Pontecagnano are mostly in line with pubertal trends emerging from other bioarchaeological studies and historical sources. The considerable inter‐individual variability in pubertal timing seen at the site probably reflects its great sociocultural heterogeneity, whilst the prolonged pubertal tempo could represent an adaptive mechanism in response to environmental disruptors. These may have included endemic diseases characteristic of Pontecagnano's marshy environment and pollutants produced by the Etruscan and Samnite metallurgical industries. Moreover, the role of catch‐up growth in favouring better pregnancy outcomes could explain why female puberty appears particularly stretched. The importance of exploring pubertal development in past societies without culturally biased assumptions is emphasised.
Asphericity of tumor [123I]mIBG uptake as a prognostic factor in high‐risk neuroblastoma
Authors: Yadgarov Mikhail , Kailash Chaurasiya , Shamanskaya Tatyana , Kachanov Denis , Likar Yury
Published: June 2022

Background

In recent years, many research groups have attempted to identify a subgroup of “ultra‐high risk” patients within the high‐risk neuroblastoma (NB) category. The aim of our study was to evaluate the prognostic significance of parameters derived from pretherapeutic 123I‐meta‐iodobenzylguanidine ([123I]mIBG) integrated single photon emission computed tomography and computed tomography in high‐risk patients with NB.

Methods

The established parameters metabolic tumor volume (MTV), maximal standardized uptake value (SUVmax) and the novel parameter tumor asphericity as well as clinical (age, stage) and genetic factors (1p/11q deletions and MYCN amplification) were analyzed in this single‐center retrospective study of high‐risk patients with newly diagnosed NB. Univariate/multivariable Cox regression and propensity score matching were performed for clinical and radiological parameters.

Results

Twenty‐eight high‐risk patients with NB were included (14 males, median age 28.8 (11.3–41.0), range 3–74 months). Multivariable analysis of “full” cohort identified high asphericity (≥65%, adjusted hazard ratio [HR] 5.32, 95% confidence interval [CI]: 1.18–24.07, p = .03) and MTV (≥50 ml, adjusted HR 4.31, 95% CI: 1.18–15.80, p = .027) as the only factors associated with worse event‐free survival. In matched cohort, tumor asphericity was a significant predictor of relapse/progression (HR 3.83, 95% CI: 1.03–14.26, p = .046).

Conclusion

In this exploratory study, imaging parameters related to tumor metabolic activity, tumor asphericity and MTV, provided prognostic value for event‐free survival in high‐risk NB patients. Asphericity ≥65% and MTV ≥50 ml may serve as additional prognostic factors to those already used.
Prospective registration of symptoms and times to diagnosis in children and adolescents with central nervous system tumors: A study of the Swedish Childhood Cancer Registry
Authors: Rask Olof , Nilsson Fredrik , Lähteenmäki Päivi , Ehrstedt Christoffer , Holm Stefan , Sandström Per‐Erik , Nyman Per , Sabel Magnus , Grillner Pernilla ,   for the Swedish Childhood CNS Tumor Working Group (VCTB)
Published: June 2022

Background

The elapsed time taken to diagnose tumors of the central nervous system in children and adolescents varies widely. The aim of the present study was to investigate such diagnostic time intervals at a national level in Sweden as they correlate with clinical features.

Methods

Data prospectively accumulated over a 4‐year period in the Swedish Childhood Cancer Registry from patients aged 0–18 years were pooled, and diagnostic time intervals were analyzed considering tumor location, tumor type, patient age and sex, initial symptoms, and clinical timelines. All six pediatric oncology centers in Sweden contributed to collection of data. Time points for calculating the total diagnostic interval (TDI) defined as the time from symptom onset to diagnosis were reported in 257 of 319 patients (81%).

Results

The time from symptom onset to the first healthcare consultation, median 2.6 weeks, did not vary significantly between patients categorized according to tumor type or location. The median TDI was 8.3 weeks for the 4‐year study period. Patients with optic pathway glioma (TDI 26.6 weeks), those with tumors of the spinal cord (TDI 25.9 weeks), and those with midline tumors (TDI 24.6 weeks) had the longest lead times. Additionally, older age, too few initial symptoms, and seeking initial redress outside an emergency ward were factors associated with a longer time to diagnosis.

Conclusion

This study identified several factors associated with delayed diagnosis of central nervous system tumors among Swedish children and adolescents. These novel data ought to help direct future efforts toward clinical improvement.
Preoperative electrodiagnostic planning for upper limb peripheral nerve transfers in cervical spinal cord injury: A narrative review
Authors: Silverman Jordan , Dengler Jana , Song Cimon , Robinson Lawrence R.
Published: June 2022

Peripheral nerve transfer (PNT) to improve upper limb function following cervical spinal cord injury (SCI) involves the transfer of supralesional donor nerves under voluntary control to intralesional or sublesional lower motor neurons not under voluntary control. Appropriate selection of donor and recipient nerves and surgical timing affect functional outcomes. Although the gold standard of nerve selection is intraoperative nerve stimulation, preoperative electrodiagnostic (EDX) evaluation may help guide surgical planning. Currently there is no standardized preoperative EDX protocol. This study reviews the EDX workup preceding PNT surgery in cervical SCI and proposes an informed EDX protocol to assist with surgical planning. The PICO (Population, Intervention, Comparison, Outcome) framework was used to formulate relevant Medical Subject Headings (MeSH) terms and identify published cases of PNT in cervical SCI in Medline, Embase, CINAHL, and Emcare databases in the last 10 years. The EDX techniques evaluating putative donor nerves, recipient nerve branches, time sensitivity of nerve transfer and other electrophysiological parameters were summarized to guide creation of a preoperative EDX protocol. Needle electromyography (EMG) was the most commonly used EDX technique to identify healthy donor nerves. Although needle EMG has also been used on recipient nerves, compound muscle action potential amplitudes may provide a more accurate determination of recipient nerve health and time sensitivity for nerve transfer. Although there has been progress in presurgical EDX evaluation, EMG and nerve conduction study approaches are variable, and each has limitations in their utility for preoperative planning. There is need for standardization in the EDX evaluation preceding PNT surgery to assist with donor and recipient nerve selection, surgical timing and to optimize outcomes. Based on results of this review, herein we propose the PreSCIse (PRotocol for Electrodiagnosis in SCI Surgery of the upper Extremity) preoperative EDX panel to achieve said goals through an interdisciplinary and patient‐centered approach.
Advancing health equity in pediatric cancer through implementation of universal family psychosocial risk screening
Authors: Deatrick Janet A. , Kazak Anne E. , Scialla Michele A. , Madden Rebecca E. , McDonnell Glynnis A. , Okonak Katherine , Barakat Lamia P.
Published: June 2022

Background

Unaddressed psychosocial risks may contribute to disparities in cancer care outcomes and may be addressed by early psychosocial risk screening. In a study implementing universal family psychosocial risk screening in 18 children's cancer programs in the United States, parents, clinicians, and organizational leaders described the importance of universal screening to health equity.

Purposes

The purposes of this study were to (1) describe the perspectives of parents, clinicians, and organizational leaders regarding the importance of universal family psychosocial risk screening in childhood cancer care and (2) identify barriers and facilitators to improving health equity and decreasing health disparities in childhood cancer through universal family psychosocial screening.

Methods

Nineteen participants (parent advocates, clinicians, leaders in professional organizations and healthcare policy) were interviewed. Directed content analysis was used to identify thematic descriptions.

Results

Theme 1: Personal (individual child and family) and systemic barriers to health care contribute to health disparities and can be identified by universal family psychosocial risk screening in pediatric cancer. Theme 2: Universal family psychosocial risk screening in pediatric cancer creates the opportunity for health equity through personalized psychosocial care. Theme 3: Recognition of health inequities and guidance from the Standards of Psychosocial Care for Children with Cancer and their Families suggest that clinicians and healthcare systems are ethically obligated to screen, provide resources, and advocate for services to meet identified needs.

Conclusions

Universal family psychosocial risk screening in pediatric oncology creates the opportunity to support efforts for health equity by guiding delivery of personalized psychosocial care.

Trial registration

NCT04446728 23 June 2020.
Cancer‐related cognitive impairment in survivors of adolescent and young adult non‐central nervous system cancer: A scoping review
Authors: Vizer Lisa M. , Mikles Sean P. , Piepmeier Aaron T.
Published: June 2022

Objectives

Cancer‐related cognitive impairments (CRCI) are common after treatment and can have important impacts on the lives of adolescent and young adult (AYA) cancer survivors—those cancer survivors diagnosed between ages 15 and 39. However, most research focuses on survivors diagnosed under age 15 or over age 39 so we know relatively little about CRCI among AYA survivors of non‐central nervous system (CNS) cancers. Here we review the research on CRCI among AYA survivors of non‐CNS cancers to determine prevalence, associated factors, and impact on survivors' lives as well as implications for future research.

Methods

In November 2021 we performed a systematic search of the literature in MEDLINE, Web of Science, PsycInfo, CINAHL, EMBASE, and Cochrane Central Register of Controlled Trials to identify peer‐reviewed English language articles describing original research with at least one cognitive outcome and conducted with AYA survivors of non‐CNS cancer diagnosed as AYAs. We screened 6003 articles and 21 met eligibility criteria. Guided by the PRISMA‐ScR Checklist, we extracted study information to meet review objectives.

Results

Most studies employed cross‐sectional surveys or interviews, though some employed longitudinal methods, neurocognitive assessments, or brain imaging. From the subset of articles that reported a prevalence we calculated a weighted mean prevalence of 25.75% and weighted median prevalence of 27.8%. The factors associated with CRCI included female gender, higher dose chemotherapy, and comorbidities. CRCI impacted the lives of AYA survivors through impaired role functioning, financial toxicity, and unmet needs.

Conclusions

CRCI is highly prevalent among non‐CNS cancer survivors diagnosed as AYAs and impacts quality of life and role functioning. This review suggests a need for further longitudinal, imaging, and mixed methods research and provision of resources to help achieve better quality of life and educational and occupational attainment during what is potentially a decades‐long survivorship period. However, although interventions might improve cognition and functioning, the review identified only one pilot study. Digital interventions may be a practical and effective option for this age group, but they have yet to be adequately investigated.
Immediate and long‐term effects of manual chest compression and decompression maneuver on patients receiving invasive mechanical ventilation
Authors: Biarzi Karla Francieli , Severo Sabrina Brandalise , Baptistella Antuani Rafael
Published: June 2022

Background

It has been reported that the manual chest compression and decompression (MCCD) maneuver can increase lung volume in patients receiving invasive mechanical ventilation (IMV), but some important questions related to this maneuver require answers: how long the effects of MCCD on lung volume remain, and whether there are effects on other respiratory and hemodynamic variables.

Methods

Patients receiving IMV support in an intensive care unit (ICU) with signs of hypoventilation, hypoexpansion, or atelectasis were eligible to receive the MCCD maneuver. Immediately before the maneuver, respiratory and hemodynamic parameters were collected. Then, 20 MCCD maneuvers were performed while measured the same parameters. After 10 min, all parameters were measured again. The primary outcome was the tidal volume (Vt) during the MCCD maneuver and after 10 min compared to the previous Vt.

Results

Of the 255 patients who were mechanically ventilated in the study period, 105 patients composed the final cohort. The MCCD increased inspiratory tidal volume (iVt), expiratory tidal volume (eVt), and chest dynamic compliance (Cdyn) during the application of the maneuver, but after 10 min, these parameters returned to their basal levels. The MCCD maneuver did not change the peak pressure, respiratory rate, peripheral oxygen saturation (SpO2), heart rate, or blood pressure. There was no difference in increased iVt in patients with sedation, respiratory comorbidity, or obesity. Further, there was no association between the iVt response to the MCCD and the admission diagnosis, and no correlation with the ICU length of stay, IMV duration, or APACHE II score.

Implications of Physiotherapy Practice

We concluded that MCCD increased iVt, eVt, and Cdyn during the application of the maneuver, but this effect was not observed after 10 min. Randomized controlled trials should be performed in the future to investigate the mechanism involved in increasing Vt and the possible impact of the MCCD maneuver on ICU outcomes.
Enhanced Water‐Splitting Application Using GaN/AlGaN Heterojunctions
Authors: Xi Xin , Chen Zhizhong , Zhao Lixia , Chen Yiyong , Nie Jingxin , Deng Chuhan , Pan Zuojian , Zhang Haodong , Kang Xiangning
Published: June 2022

Herein, a research is conducted on a AlGaN/GaN photoanode by depositing AlGaN with different thicknesses on the GaN epitaxial layer. The result shows that GaN with a thin AlGaN coating has significant enhancement on water‐splitting performance. The photocurrent of GaN photoanode with 5 nm AlGaN layer can be enhanced by a factor of 1.8, compared with planar GaN. The high performance of the AlGaN/GaN heterojunction photoanode is mainly attributed to the high electron–hole density generated at the interface between GaN and AlGaN layers and the quantum tunneling transport of photogenerated carriers. The high concentration of carriers can not only enhance the mobility of carriers but also increase the electron–hole pairs for the water oxidation reaction. The quantum tunneling effect can facilitate the carriers through the high‐energy barrier of AlGaN for photolysis reaction with electrolyte. Herein, a promising method for the application of GaN in efficient water splitting is provided.
A Tensor‐based Regression Approach for Human Motion Prediction
Authors: Gril Lorena , Wedenig Philipp , Torkar Chris , Kleb Ulrike
Published: June 2022

Collaborative robotic systems will be a key enabling technology for current and future industrial applications. The main aspect of such applications is to guarantee safety for humans. To detect hazardous situations, current commercially available robotic systems rely on direct physical contact to the co‐working person. To further advance this technology, there are multiple efforts to develop predictive capabilities for such systems. Using motion tracking sensors and pose estimation systems combined with adequate predictive models, potential episodes of hazardous collisions between humans and robots can be predicted. Based on the provided predictive information, the robotic system can avoid physical contact by adjusting speed or position. A potential approach for such systems is to perform human motion prediction with machine learning methods like artificial neural networks (NNs). In our approach, the motion patterns of past seconds are used to predict future ones by applying a linear Tensor‐on‐Tensor Regression model, selected according to a similarity measure between motion sequences obtained by dynamic time warping (DTW). For test and validation of our proposed approach, industrial pseudo assembly tasks were recorded with a motion capture system, providing unique traceable Cartesian coordinates for each human joint. The prediction of repetitive human motions associated with assembly tasks, whose data vary significantly in length and have highly correlated variables, has been achieved in real time.
Effects of flow regulation and drought on geomorphology and floodplain habitat along the Colorado River in Canyonlands National Park, Utah
Authors: Grams Paul E. , Head Eric , Mueller Erich R.
Published: June 2022

Streamflow regulation compounded by regional drought has resulted in up to 22% reduction in channel width, changes in channel planform, expansion of riparian vegetation, and alterations to floodplain habitat on the Colorado River in Meander Canyon, Utah. Although some changes in channel width occurred between the 1940s and 1980s, coinciding with major phases of upstream water development, larger decreases in channel width occurred between 1993 and 2006 during periods of exceptionally low annual floods. These findings illustrate that low runoff associated with regional drought and climate change may cause changes in river channel form that accelerate and compound the effects of upstream water development. Declining peak flows have also resulted in disconnection between the wetted channel and floodplains, where inundated back‐levee depressions provide habitat used by two species of threatened and endangered native fish. Despite this disconnection, some back‐levee depressions on the floodplain continue to be inundated by ~1.5‐year recurrence floods via connections created by tributary mouths, floodplain outflow channels, and levee breaches excavated by resident beaver. These changes are shown by analysis of aerial images, high‐resolution bathymetric and topographic measurements, and 2‐dimensional streamflow modeling.
Effects of hydropeaking on drift, stranding and community composition of macroinvertebrates: A field experimental approach in three regulated Swiss rivers
Authors: Tonolla Diego , Dossi Florian , Kastenhofer Olivier , Doering Michael , Hauer Christoph , Graf Wolfram , Schülting Lisa
Published: June 2022

Hydropeaking operation leads to fluctuations in wetted area between base and peak flow and increases discharge‐related hydraulic forces (e.g. flow velocity). These processes promote macroinvertebrate drift and stranding, often affecting benthic abundance and biomass. Our field experimental study—conducted in three hydropeaking‐regulated Swiss rivers—aimed to quantify (a) the short‐term effects of the combined increase in flow amplitude and up‐ramping rate based on macroinvertebrate drift and stranding, as well as (b) long‐term effects based on the established community composition. Hydropeaking led to increased macroinvertebrate drift compared to base flow and to unaffected residual flow reaches. Moreover, stranding of macroinvertebrates was positively related to drift, especially during the up‐ramping phase. Flow velocity and up‐ramping rate were identified as major determinants for macroinvertebrate drift, while flow ratio and down‐ramping rate for stranding. Particularly high sensitivity towards hydropeaking was found for Limnephilidae, whereas Heptageniidae seemed to be resistant in respect to short‐ and long‐term hydropeaking effects. In the long‐term, hydropeaking did not considerably reduce benthic density of most taxa, especially of some highly resistant and resilient taxa such as Chironomidae and Baetidae, which dominated the community composition even though they showed comparably high drift and stranding responses. Therefore, we argue that high drift and/or stranding, especially of individual‐rich taxa, does not necessarily indicate strong hydropeaking sensitivity. Finally, our results demonstrate the necessity to consider the differences in river‐specific morphological complexity and hydropeaking intensity, since these factors strongly influence the community composition and short‐term drift and stranding response of macroinvertebrates to hydropower pressure.