bluuebunny/crossref_metadata_2025 huggingface dataset:
Recruitment, outcomes, and toxicity trends in phase I oncology trials: Six‐year experience in a large institution
Authors: Menon Siddharth , Davies Amy , Frentzas Sophia , Hawkins Cheryl‐Ann , Segelov Eva , Day Daphne , Markman Ben
Published: July 2021

Background

With the rapid influx of novel anti‐cancer agents, phase I clinical trials in oncology are evolving. Historically, response rates on early phase trials have been modest with the clinical benefit and ethics of enrolment debated. However, there is a paucity of real‐world data in this setting.

Aim

To better understand the changing landscape of phase I oncology trials, we performed a retrospective review at our institution to examine patient and trial characteristics, screening outcomes, and treatment outcomes.

Methods and results

We analyzed all consecutive adult patients with advanced solid organ malignancies who were screened across phase I trials from January 2013 to December 2018 at a single institution. During this period, 242 patients were assessed for 28 different trials. Median age was 64 years (range 30–89) with an equal sex distribution. Among 257 screening visits, the overall screen failure rate was 18%, resulting in 212 patients being enrolled onto a study. Twenty‐six trials (93%) involved immunotherapeutic agents or molecular targeted agents either alone or in combination, with only two trials of cytotoxic agents (7%). Twenty‐two (13.4%) of the 209 treated patients experienced a total of 33 grade 3 or higher treatment‐related adverse events. There was one treatment‐related death (0.5%). Of 190 response‐evaluable patients, 7 (4%) had a complete response, 34 (18%) a partial response, and 59 (31%) experienced stable disease for a disease control rate of 53%. The median overall survival for our cohort was 8.0 (95% CI: 6.8–9.2) months.

Conclusion

The profile of phase I trials at our institution are consistent with the changing early drug development landscape. Response rates and overall survival in our cohort are superior to historically reported rates and comparable to contemporaneous studies. Severe treatment‐related toxicity was relatively uncommon, and treatment‐related mortality was rare.
Impact of consensus guidelines for breast‐conserving surgery in patients with ductal carcinoma in situ
Authors: Tremelling Abigail , Aft Rebecca L. , Cyr Amy E. , Gillanders William E. , Glover‐Collins Katherine , Herrmann Virginia , Margenthaler Julie A.
Published: July 2021

Background

Consensus guidelines published in 2016 recommended a 2 mm free margin as the standard for negative margins in patients undergoing breast‐conserving surgery (BCS) for ductal carcinoma in situ (DCIS). The goal of the guideline recommendation was standardization of re‐excision practices.

Aims

To evaluate the impact of this consensus guideline on our institutional practices.

Methods

We identified all patients at our institution with pure DCIS who were initially treated with BCS from September 2014 to August 2018 using a prospectively‐maintained institutional database. A retrospective chart review was performed to determine margin status and re‐excision rates during the 2 years before and the 2 years after the guideline was published in order to determine the effect on our re‐excision rates. Close margins were defined as <2 mm.

Results

In the 2 years before the consensus guideline was published, 184 patients with DCIS underwent BCS. Twenty‐six patients had positive margins and 24 underwent re‐excision, including three who had completion mastectomy. Of the remaining 159 patients, 76 had ≥2 mm (negative) margins. The remaining 82 patients had close margins and 48 of these patients (58.5%) underwent re‐excision, including one who had a completion mastectomy. Excluding the patients with positive margins, our re‐excision rate was 30.4% prior to the guideline. In the 2 years after the consensus guideline was published, 192 patients with DCIS underwent initial BCS. Twenty‐four patients had positive margins and 22 underwent re‐excision, including three who had completion mastectomy. Of the remaining 168 patients, 95 patients had ≥2 mm (negative) margins. The remaining 73 patients had close margins and 45 of those patients (61.6%) underwent re‐excision, including six who had completion mastectomy. Excluding the patients with positive margins, our re‐excision rate was 26.8% after the guideline.

Conclusions

Our institution's re‐excision rate did not change significantly during the 2 years before and after the publication of the consensus guideline on adequate margins for patients undergoing BCT for DCIS. Our overall re‐excision rate decreased slightly. However, of the patients who had close margins, a larger proportion underwent re‐excision after the guideline was published. The guideline publication appears to have affected our institutional practices slightly, but not dramatically as many of our surgeons' practices were comparable to the guideline recommendations prior to 2016. We continue to use clinical judgment based on patient and tumor characteristics in deciding which patients will benefit from margin re‐excision.
Neutrophils and their role in the aetiopathogenesis of type 1 and type 2 diabetes
Authors: Giovenzana Anna , Carnovale Debora , Phillips Brett , Petrelli Alessandra , Giannoukakis Nick
Published: July 2021

Multiple and complex aetiological processes underlie diabetes mellitus, which invariably result in the development of hyperglycaemia. Although there are two prevalent distinct forms of the disease, that is, type 1 and type 2 diabetes, accumulating evidence indicates that these syndromes share more aetiopathological mechanisms than originally thought. This compels a rethinking of the approaches to prevent and treat the different manifestations of what eventually becomes a hyperglycaemic state. This review aims to address the involvement of neutrophils, the most abundant type of granulocytes involved in the initiation of the acute phase of inflammation, in the aetiopathogenesis of diabetes mellitus, with a focus on type 1 and type 2 diabetes. We review the evidence that neutrophils are the first leucocytes to react to and accumulate inside target tissues of diabetes, such as the pancreas and insulin‐sensitive tissues. We then review available data on the role of neutrophils and their functional alteration, with a focus on NETosis, in the progression towards clinical disease. Finally, we review potential approaches as secondary and adjunctive treatments to limit neutrophil‐mediated damage in the prevention of the progression of subclinical disease to clinical hyperglycaemia.
Environment, vector, or host? Using machine learning to untangle the mechanisms driving arbovirus outbreaks
Authors: Alkhamis Moh A. , Fountain‐Jones Nicholas M. , Aguilar‐Vega Cecilia , Sánchez‐Vizcaíno José M.
Published: July 2021

Climatic, landscape, and host features are critical components in shaping outbreaks of vector‐borne diseases. However, the relationship between the outbreaks of vector‐borne pathogens and their environmental drivers is typically complicated, nonlinear, and may vary by taxonomic units below the species level (e.g., strain or serotype). Here, we aim to untangle how these complex forces shape the risk of outbreaks of Bluetongue virus (BTV); a vector‐borne pathogen that is continuously emerging and re‐emerging across Europe, with severe economic implications. We tested if the ecological predictors of BTV outbreak risk were serotype‐specific by examining the most prevalent serotypes recorded in Europe (1, 4, and 8). We used a robust machine learning (ML) pipeline and 23 relevant environmental features to fit predictive models to 24,245 outbreaks reported in 25 European countries between 2000 and 2019. Our ML models demonstrated high predictive performance for all BTV serotypes (accuracies > 0.87) and revealed strong nonlinear relationships between BTV outbreak risk and environmental and host features. Serotype‐specific analysis suggests, however, that each of the major serotypes (1, 4, and 8) had a unique outbreak risk profile. For example, temperature and midge abundance were as the most important characteristics shaping serotype 1, whereas for serotype 4 goat density and temperature were more important. We were also able to identify strong interactive effects between environmental and host characteristics that were also serotype specific. Our ML pipeline was able to reveal more in‐depth insights into the complex epidemiology of BTVs and can guide policymakers in intervention strategies to help reduce the economic implications and social cost of this important pathogen.
Pilot outcomes from a multidisciplinary telehealth versus in‐person intensive outpatient program for eating disorders during versus before the Covid‐19 pandemic
Authors: Levinson Cheri A. , Spoor Samantha P. , Keshishian Ani C. , Pruitt Alexandria
Published: July 2021

Introduction

Eating disorders (EDs) are serious mental illnesses with high rates of mortality, morbidity, and personal and societal costs. Onset of the Covid‐19 pandemic led to increased ED diagnoses in the general public, as well as worsening of ED symptoms in those with an existing ED diagnosis. Heightened prevalence and severity of EDs during the pandemic is complicated by the fact that traditional modes of ED care (specialty intensive treatment provided by a multidisciplinary team) have been difficult to access during the pandemic.

Methods

The current between‐groups study (N = 93 ED) tested a multidisciplinary intensive outpatient program (IOP) delivered via in‐person (pre‐pandemic; n = 60) and virtually via telehealth (during the pandemic; n = 33).

Results

We found no differences in outcomes via delivery mode, such that regardless of in‐person versus telehealth programming, ED symptoms, depression, and perfectionism significantly decreased and body mass index significantly increased.

Conclusions

Our findings suggest that a multi‐disciplinary telehealth ED IOP program is feasible and has comparable outcomes to in‐person IOP treatment. These findings have implications for treatment beyond the pandemic, suggesting that adoption of telehealth IOPs is warranted. Such delivery modes of intensive treatments for EDs could be expanded to reach underserved populations, especially in rural areas where treatment is often difficult to access.
Streetlights positively affect the presence of an invasive grass species
Authors: Murphy Shannon M. , Vyas Dhaval K. , Hoffman Jennifer L. , Jenck Clara S. , Washburn Brooke A. , Hunnicutt Kelsie E. , Davidson Angie , Andersen Jasmine M. , Bennet Rachel K. , Gifford Amarin , Herrera Mia , Lawler Braelynn , Lorman Sophie , Peacock Vanessa , Walker Lyndi , Watkins Esme , Wilkinson Lakyn , Williams Zariah , Tinghitella Robin M.
Published: July 2021

Anthropogenic disturbances associated with urban ecosystems can create favorable conditions for populations of some invasive plant species. Light pollution is one of these disturbances, but how it affects the growth and establishment of invasive plant populations is unknown. Cheatgrass (Bromus tectorum) is a problematic invasive species where it has displaced native grassland communities in the United States, but to our knowledge, there have been no studies of the ecological factors that affect cheatgrass presence in urban ecosystems. We conducted field surveys in urban alleys in Denver, Colorado, to compare the presence of cheatgrass at sites with and without artificial light at night (hereafter artificial light) from streetlights. These streetlights are mounted on utility poles, which cause ground disturbance when installed in alleys; we were able to test the independent effect of poles on cheatgrass establishment because not all poles have streetlights on them. We found that cheatgrass was positively associated with the presence of streetlights and to a lesser extent poles. In addition to cheatgrass, we also found that other plants were positively associated with the presence of both poles and streetlights. Our results suggest that artificial light may benefit the occurrence of cheatgrass and other plant species in urban settings. While invasive populations of cheatgrass in wild habitats attract the most attention from managers, we suggest more consideration for this grass in urban environments where its growth and establishment benefit from anthropogenic changes.
Natural distinction of carbon and nitrogen isotopic niches in common fish species across marine biotopes in the Yellow River estuary
Authors: Qu Pei , Pang Min , Qu Fangyuan , Li Zhao , Xiao Meng , Zhang Zhaohui
Published: July 2021

Stable isotope analysis is a universally recognized and efficient method of indicating trophic relationships that is widely applied in research. However, variation in stable isotope ratios may lead to inaccuracies due to the effects of complex environmental conditions. This research compared the carbon and nitrogen isotopic niches of fish communities between diverse biotopes around the Yellow River estuary and adjacent sea areas, with the aim of revealing distinctions in stable isotopic niche metrics, trophic positions, and feeding preferences. Our analysis of the food source contribution indicated that allochthonous sources were considered major energy sources in estuarine areas directly affected by Yellow River‐diluted water, while autochthonous benthic and pelagic producers dominated carbon input into the food web in Laizhou Bay and the open water. A significant variation in the fish δ15N characteristic was found within estuarine adjacent regions, so, together with the results from previous studies, we deemed the local high concentration of dissolved inorganic nitrogen as the original trigger of the abnormal δ15N characteristic in fishes via a transport process along food chains. These results provide a new perspective on the natural distinction of carbon and nitrogen isotopic niches. The detailed data reported here enhance our understanding of variations in fish communities in estuarine ecosystems.
Risk of mortality among inpatients with COVID‐19 and type 2 diabetes: National data from Kuwait
Authors: Al‐Ozairi Ebaa , Brown Rosemary , Hamdan Yasmine , Alabdullah Lulwa , Voase Nia , Al Kandari Jumana , Alsaeed Dalal , Al Ozairi Abdulla , Hasan Amal , Al‐Mulla Fahd , Katikireddi Srinivasa Vittal , Gray Stuart R. , Gill Jason M. R. , Celis‐Morales Carlos A. , Sattar Naveed , Welsh Paul
Published: July 2021

Introduction

To investigate type 2 diabetes as a risk factor for COVID‐19 death following hospital admission in Kuwait.

Methods

A retrospective cohort study using data from a central hospital that cared for all hospitalized COVID‐19 patients in Kuwait. We investigated the association between type 2 diabetes, with COVID‐19 mortality using multiply imputed logistic regression and calculated the population attributable fraction.

Results

A total of 5333 patients were admitted with COVID‐19, of whom 244 died (4.6%). Diabetes prevalence was 24.8%, but 53.7% of those who died had diabetes. After adjusting for age, sex, ethnicity and other comorbidities, diabetes was associated with death (OR 1.70 [95% CI 1.23, 2.34]) and admission to the intensive care unit more than 3 days after initial admission (OR 1.78 [95% CI 1.17, 2.70]). Assuming causality, the population attributable fraction for type 2 diabetes in COVID‐19 death was 19.6% (95% CI 10.8, 35.6).

Conclusion

Type 2 diabetes is a strong risk factor for COVID‐19 death in the Middle East. Given the high prevalence of type 2 diabetes in the Middle East, as well as many Western countries, the public health implications are considerable.
Protective effect of Salidroside on hypoxia‐related liver oxidative stress and inflammation via Nrf2 and JAK2/STAT3 signaling pathways
Authors: Xiong Yanlei , Wang Yueming , Xiong Yanlian , Teng Lianghong
Published: July 2021

High‐altitude hypoxia‐induced oxidative stress and inflammation played an essential role in the incidence and development of liver injury. Salidroside (Sal), a phenylpropanoid glycoside extracted from the plant Rhodiola rosea, has recently demonstrated antioxidant, anti‐inflammatory, and antihypoxia properties. Herein, we hypothesized that salidroside may alleviate hypoxia‐induced liver injury via antioxidant and antiinflammatory‐related pathways. A high‐altitude hypoxia animal model was established using hypobaric chamber. Male SD rats were randomly divided into the control group, hypoxia group, control +Sal group, and hypoxia +Sal group. Salidroside treatment significantly inhibited hypoxia‐induced increases of serum and hepatic pro‐inflammatory cytokines release, hepatic ROS production and MDA contents; attenuated hypoxia‐induced decrease of hepatic SOD, CAT, and GSH‐Px activities. Furthermore, salidroside treatment also potentiated the activation of Nrf2‐mediated anti‐oxidant pathway, as indicated by upregulation of n‐Nrf2 and its downstream HO‐1 and NQO‐1. In vitro study found that blocking the Nrf2 pathway using specific inhibitor ML385 significantly reversed the protective effect of salidroside on hypoxia‐induced liver oxidative stress. In addition, salidroside treatment significantly inhibited hepatic pro‐inflammatory cytokines release via JAK2/STAT3‐mediated pathway. Taken together, our findings suggested that salidroside protected against hypoxia‐induced hepatic oxidative stress and inflammation via Nrf2 and JAK2/STAT3 signaling pathways.
Sentinel lymph node biopsy versus elective neck dissection in squamous cell carcinoma of the oral cavity with a clinically N0 neck: Systematic review and meta‐analysis of prospective studies
Authors: Ding Zhangfan , Li Yike , Pan Xun , Xuan Ming , Xie Huixu , Wang Xiaoyi
Published: July 2021

Sentinel lymph node biopsy (SLNB) is an emerging strategy for managing early‐stage oral squamous cell carcinoma (SCC) with a clinically N0 (cN0) neck. However, the role of SLNB in this scenario is debatable. Herein, relevant literature was systematically reviewed, and a meta‐analysis was performed to evaluate the potential dividends of SLNB compared to elective neck dissection (END) for these patients. The meta‐analysis, including six prospective studies, showed comparable results of the two management strategies in terms of regional recurrence (risk ratio [RR] = 0.99; 95% confidence interval [CI], 0.58–1.70), 5‐year disease‐free survival (RR = 0.99; 95% CI, 0.87–1.11), and 5‐year overall survival (RR = 1.01; 95% CI, 0.90–1.13). Fewer adverse events occurred in the SLNB arm than in the END arm (RR = 0.12; 95% CI, 0.02–0.70). Overall, SLNB results in as favorable an oncologic prognosis for patients with cN0 oral SCC as END, while significantly lessening side effects and unnecessary surgeries.
Analysis of HBsAg Immunocomplexes and cccDNA Activity During and Persisting After NAP‐Based Therapy
Authors: Bazinet Michel , Anderson Mark , Pântea Victor , Placinta Gheorghe , Moscalu Iurie , Cebotarescu Valentin , Cojuhari Lilia , Jimbei Pavlina , Iarovoi Liviu , Smesnoi Valentina , Musteata Tatina , Jucov Alina , Dittmer Ulf , Gersch Jeff , Holzmayer Vera , Kuhns Mary , Cloherty Gavin , Vaillant Andrew
Published: July 2021

Therapy with nucleic acid polymers (NAPs), tenofovir disoproxil fumarate (TDF), and pegylated interferon (pegIFN) achieve high rates of HBsAg loss/seroconversion and functional cure in chronic hepatitis B virus (HBV) infection. The role of hepatitis B surface antigen (HBsAg) seroconversion and inactivation of covalently closed circular DNA (cccDNA) in establishing functional cure were examined. Archived serum from the REP 401 study was analyzed using the Abbott ARCHITECT HBsAg NEXT assay (Chicago, IL), Abbott research use–only assays for HBsAg immune complexes (HBsAg ICs), circulating HBV RNA, and the Fujirebio assay for hepatitis B core‐related antigen (HBcrAg; Malvern, PA). HBsAg became < 0.005 IU/mL in 23 participants during NAP exposure, which persisted in all participants with functional cure. HBsAg IC declined during lead‐in TDF monotherapy and correlated with minor declines in HBsAg. Following the addition of NAPs and pegIFN, minor HBsAg IC increases (n = 13) or flares (n = 2) during therapy were not correlated with HBsAg decline, hepatitis B surface antibody (anti‐HBs) titers, or alanine aminotransferase. HBsAg IC universally declined during follow‐up in participants with virologic control or functional cure. Universal declines in HBV RNA and HBcrAg during TDF monotherapy continued with NAP + pegIFN regardless of therapeutic outcome. At the end of therapy, HBV RNA was undetectable in only 5 of 14 participants with functional cure but became undetectable after removal of therapy in all participants with functional cure. Undetectable HBV RNA at the end of therapy in 5 participants was followed by relapse to virologic control or viral rebound. Conclusion: Anti‐HBs‐independent mechanisms contribute to HBsAg clearance during NAP therapy. Inactivation of cccDNA does not predict functional cure following NAP‐based therapy; however, functional cure is accompanied by persistent inactivation of cccDNA. Persistent HBsAg loss with functional cure may also reflect reduction/clearance of integrated HBV DNA. Clinicaltrials.org number NCT02565719.
Engagement, satisfaction, retention and behavioural outcomes of linguistically diverse mothers and infants participating in an Australian early obesity prevention trial
Authors: Marshall Sarah , Xu Huilan , Taki Sarah , Laird Yvonne , Love Penelope , Wen Li Ming , Rissel Chris
Published: July 2021

Background

Early obesity prevention research interventions in Australia generally expect participants to be able to communicate in English, but do not account for other languages. This study aimed to investigate engagement, satisfaction, retention and behavioural outcomes of linguistically diverse participants from a mainstream early childhood obesity prevention trial.

Methods

Healthy Beginnings is a nurse‐led intervention based in Sydney, supporting families with optimal infant feeding and active play via telephone. This secondary analysis assessed participant engagement in the nurse telephone calls (call completions), satisfaction and behavioural outcomes (6‐ and 12‐month survey data) and retention (survey completions), in the first year of life according to participants’ language spoken at home (English or other language).

Results

Of 1155 mothers, 533 (46%) spoke a language other than English at home. Significantly fewer mothers speaking a language other than English completed the 6‐month survey (79%) compared to those speaking English (84%), yet mothers speaking a language other than English who completed the program were more satisfied with the program overall. Significantly fewer mothers speaking a language other than English completed the final four nurse calls (of six) (56%‐65%) compared to those speaking English (70%‐80%). Adjusted odds ratios showed selected behavioural outcomes were significantly more positive for participants speaking English at home.

Conclusions

Healthy Beginnings trial participants who spoke a language other than English at home had less favourable engagement, retention and behavioural outcomes compared to those who spoke English.

So what?

Early obesity prevention interventions should consider cultural adaptations to improve engagement and effectiveness among culturally and linguistically diverse families.
Gesture recognition in somatosensory game via Kinect sensor
Authors: Lv Wei
Published: July 2021

With the development of computer technology, the means of human‐computer interaction are constantly updated. The development trend is from human to computer to constantly adapt human habits. In the human‐computer interaction, the somatosensory sensor technology is used to track and analyze human actions through computer vision technology. This paper adopts somatosensory sensor to implement gesture recognition, which is an important way in human‐computer interaction. The somatosensory sensor can obtain the depth information and bone information in the human‐computer interaction. First, the gesture is decomposed into a gesture sequence consisting of micro gestures to describe different directions. Then, the gesture sequence is compared with the gesture templates. The gesture is determined by the pattern matching result. The experimental results show that more than 92% gestures can be identified by proposed recognition method.
The effects of the molecular weight of chitosan on the tissue inflammatory response
Authors: Ribeiro José Carlos Viana , Forte Tereza Cristina Marques , Tavares Samia Jéssica Silva , Andrade Fábia Karine , Vieira Rodrigo Silveira , Lima Vilma
Published: July 2021

The molecular weight of chitosan (CS) may affect its physical properties and its ability to induce an appropriate host response. The biocompatibilities of CS membranes of low (LMWCS) and high (HMWCS) molecular weight were investigated by inserting these materials into the subcutaneous tissue of rats for 1–28 days and evaluating leukocyte infiltration, granulation tissue, fibrosis, arginase‐1 immunostaining, as well as nuclear factor‐κB (NF‐κΒ) and fibroblast growth factor (FGF)‐2 expressions. Both CS membranes induced a peak of leukocyte infiltration on the first day of insertion and stimulated granulation and fibrous tissue generation when compared to control. LMWCS induced more collagen deposition a week earlier, when compared to the control and HMWCS membrane. The membranes also increased arginase‐1 immunostaining, a M2 macrophage marker. M2 macrophage is recognized as anti‐inflammatory and pro‐regenerative. NF‐κB is an essential biomarker of the inflammatory process and induces the expression of several pro‐inflammatory cytokines. The LMWCS membrane reduced inflammation, as indicated by a reduced nucleus/cytoplasm NF‐κB ratio in surrounding tissue from days 7 to 14 when compared to control. On the first day, the expression of FGF‐2, a biomarker of inflammatory resolution, was increased in the tissue of the LWMCS group, when compared with HMWCS, which was consistent with the type I collagen deposition. Thus, LWMCS was associated with a prior reduction of the inflammatory response and improved wound healing.
Intramolecular interactions play key role in stabilization of pHLIP at acidic conditions
Authors: Frazee Nicolas , Mertz Blake
Published: July 2021

The pH‐Low Insertion Peptide (pHLIP) is a membrane‐active peptide that spontaneously folds into a transmembrane α‐helix upon acidification. This activity enables pHLIP to potentially act as a vector for drugs related to diseases characterized by acidosis such as cancer or heart ischemia. Presently, due to aggregation‐based effects, formulations of pHLIP are only viable at near‐μM concentrations. In addition, since most of pHLIP's measurable qualities involve a membrane, probing the details of pHLIP in the interstitial region is difficult. In attempts to shed light on these issues, we performed constant pH molecular dynamics simulations on pHLIP as well as P20G, a variant with increased helicity, in solution at 0 and 150 mM NaCl over a broad range of pHs. In general, the addition of ions reduced the effective pKa of the acidic residues in pHLIP. P20G exhibits a higher helicity than pHLIP in general and is more compact than pHLIP at pH values under 4. In terms of charge effects, sodium cations localized predominantly to the C‐terminus of the peptide with a high density of acidic residues. Additionally, the salt bridge between R11 and D14 is by far the most favored and particularly so with pHLIP at 150 mM NaCl. We expect that this approach will be a valuable tool to screen variants of pHLIP for favorable properties in solution, an aspect of pHLIP design that to this point has largely been neglected.
2‐Hydroxy‐5‐nitropyridine and 5‐nitro‐2‐pyridone: Tautomerism, infrared, Raman, and NMR spectral interpretations, normal coordinate analysis, and DFT calculations
Authors: Mohamed Tarek A. , Shaaban Ibrahim A. , Soliman Usama A. , Zoghaib Wajdi M.
Published: July 2021

Raman (3700–50 cm−1) and infrared (IR) (4000–230 cm−1) spectra of 2‐hydroxy‐5‐nitropyridine (HNP; C5H4N2O3) have been recorded in the solid phase in addition to 1H, 13C, and 15N nuclear magnetic resonance (NMR) spectra of the sample in dimethyl sulfoxide‐d6 (DMSO‐d6). Initially, keto and enol tautomeric forms were proposed owing to proton transfer from the hydroxyl group to pyridine nitrogen atom. Quantum mechanical calculations based on density functional theory (DFT; B3LYP, ωB97XD, and mPW1PW91) were carried out using 6‐31G(d) and 6‐311++G(d,p) basis sets favoring keto‐NPO, 5‐nitro‐2‐pyridone, tautomer by ~0.857–1.345 kcal/mol with minor enol‐HNP in the gas phase. Moreover, 1H, 13C, and 15N NMR chemical shifts were predicted using gauge‐invariant atomic orbital‐DFT calculation at 6‐311++G(d,p) basis set using integral equation formalism of the polarization continuum solvation model including solvent effects. The calculated chemical shifts and spin–spin coupling constants (JHH) for keto tautomer better resemble those experimentally observed rather than the enol form. The observed IR/Raman bands were assigned quantitatively to their normal modes based on the calculated vibrational frequencies, force constants in internal coordinates, normal coordinate analysis, and potential energy distributions. Finally, the nitro and hydroxyl barriers to internal rotations were predicted via a relaxed potential energy surface scan using B3LYP/6‐311++G(d,p) calculations. The results are reported herein and compared with similar molecules whenever appropriate.
Aberrant expression of HIF3A in plasma of patients with non‐small cell lung cancer and its clinical significance
Authors: Wei Liang , Yuan Na , Chen Yingying , Gong Pingping
Published: July 2021

Background

Hypoxia‐inducible factors (HIFs) have been evaluated in various cancers and diseases. However, the specific role of hypoxia‐inducible factor 3 alpha (HIF3A) in non‐small cell lung cancer (NSCLC) remains controversial.

Materials and Methods

We investigated HIF3A mRNA expression in the plasma and tumor tissues of patients with NSCLC and explored its clinical significance. Plasma samples from 103 cases of lung adenocarcinoma (LUAD) and 96 cases of lung squamous cell carcinoma (LUSC), and tumor‐adjacent normal tissues from 58 LUAD and 62 LUSC cases were retrospectively evaluated at the No.8 People's Hospital of Qing Dao. HIF3A expression was explored using RT‐qPCR. The clinical significance of HIF3A was evaluated in the plasma and tumor tissues using the receiver operating curve (ROC) and the area under the curve (AUC).

Results

Hypoxia‐inducible factor 3 alpha expression was notably downregulated in the plasma or tumor tissues of patients with LUAD and LUSC, compared with the healthy control group or adjacent normal tissues. Furthermore, HIF3A expression had a significant positive correlation in the plasma and tumor tissues of LUAD and LUSC patients. Meanwhile, the ROC‐AUCs achieved a significantly higher range, from 0.84 to 0.93, with the plasma or tumor tissues of NSCLC patients. Thus, HIF3A expression was not only correlated with plasma and tumor tissues, but also showed potential significance in NSCLC.

Conclusion

Hypoxia‐inducible factor 3 alpha is aberrantly detectable in NSCLC patients in the plasma and tumor tissues. HIF3A may be involved in hypoxic responses during the development and occurrence of NSCLC.
Natural history of fetal ovarian cysts in the prenatal and postnatal periods
Authors: Akalin Munip , Demirci Oya , Dayan Eda , Odacilar Ali Sahap , Ocal Aydin , Celayir Aysenur
Published: July 2021

Purpose

To determine the natural history of fetal ovarian cysts and to investigate whether the prognosis can be predicted by prenatal ultrasonography (US).

Methods

This retrospective study includes cases of fetal ovarian cysts diagnosed by prenatal US over a 6‐year period. Cases were divided into four subgroups of cysts (small and simple, small and complex, large and simple, large and complex) according to their size and echotexture. US examinations were repeated every 2 weeks from the time of diagnosis to treatment.

Results

A total of 37 cases were included in the study. 32.4% of the cases regressed spontaneously in the prenatal period and 32.4% did so in the infantile period. Prenatal resolution occurred more frequently with small cysts than with large cysts (p = 0.03). Neonates with complex cysts required surgical treatment more often than neonates with simple cysts (p = 0.009). 27.0% of the cases underwent surgery due to ovarian torsion. The torsion rate of fetal ovarian cysts that progressed in the prenatal period was significantly higher than in the case of stable cysts (p = 0.001).

Conclusion

The size of the fetal ovarian cysts, their US appearance and the progression of the cysts during follow‐up are the main determinants of the neonatal outcome.
Investigation of structural, optical, and electrical properties of the (CuO/ZnO:Al/SnO2:F) heterostructure thin films using the spin coating method
Authors: Kara Ilker
Published: July 2021

In this study, (CuO/ZnO:Al) heterostructure thin films were grown on SnO2:F‐coated glass substrate by using the spin coating method. To investigate the effects of thickness on (CuO/ZnO:Al) heterostructure, ZnO:Al films were deposited in different thicknesses. The structural, optical, surface, and electrical properties of these heterostructure were examined in detail. The structural and optical properties of obtained heterostructure were examined by X‐ray diffraction and UV–VIS spectrophotometer, respectively. The surface properties were analyzed by using atomic force microscope and scanning electron microscope. The electrical properties of these heterostructure were determined by current–voltage (I–V) characteristics at room temperature in dark. The electrical parameters (i.e., ideality factor and barrier height) were calculated by termoionic emission theory by using I–V measurement data. The change for thickness of n‐type AZO layer in the (CuO/ZnO:Al/SnO2:F) heterostructure caused significant changes in its physical properties.
An observational study to determine volume changes in the functional liver remnant following portal vein embolization
Authors: Dhurandhar Vikrant , Waugh Richard , Ahmed Sulman , Mantrala Suchitra , Chaganti Joga
Published: July 2021

Background and Aim

Portal vein embolization (PVE) prior to hepatic resection reduces the risk of hepatic insufficiency in the postoperative period by redistributing blood from the embolized unhealthy liver to the healthy liver, termed the functional liver remnant (FLR). A retrospective analysis of liver volumes after embolization in a single institution was performed to identify change in volume of the FLR and determine factors affecting this change.

Methods

Between 2013 and 2015, 21 patients undergoing PVE followed by hepatic resection for varied indications (colorectal metastases, hepatocellular carcinoma, cholangiocarcinoma, etc.) were included in this study. n‐butyl cyanoacrylate glue diluted with Lipiodol (35–45% strength) along with 75–100 μm of polyvinyl alcohol particles were used for embolization. Liver volumetric determination was performed before and after PVE and volume changes in the FLR were analyzed. Biochemical factors and factors affecting FLR hypertrophy were also analyzed.

Results

Majority of the patients (n = 18) underwent right‐lobe embolization. All were performed using the ipsilateral approach. No major complications occurred with only one patient developing post‐procedural ascites requiring percutaneous draining. A significant increase in the mean volume of the FLR by 63.7% ± 91.6%, P = 0.001 was noted after PVE. The FLR/total liver volume (TLV) increased significantly by 17% ± 18%. No significant demographic factors affected FLR hypertrophy and no significant biochemical changes were noted. Thirteen patients were successfully operated on after embolization.

Conclusions

PVE is effective in inducing significant hypertrophy of the future FLR, prior to hepatic resection in our institution.
Safety of laparoscopic hepatectomy in patients with severe comorbidities ‐ A propensity score matched analysis
Authors: Heise Daniel , Bednarsch Jan , Kroh Andreas , Eickhoff Roman , Coolsen Marielle M. E. , van Dam Ronald , Lang Sven Arke , Neumann Ulf Peter , Ulmer Florian
Published: July 2021

Background

Laparoscopic hepatectomy (LH) is nowadays considered as the standard of care for various liver malignancies. However, studies focusing on perioperative outcome after LH in patients with severe comorbidities are still sparse.

Methods

247 patients, who underwent LH between January 2016 and March 2020 at European surgical center Aachen Maastricht (ESCAM) were retrospectively analyzed regarding surgical outcome. All patients were categorized according to the ASA guidelines and a propensity score matched (PSM) analysis was performed to compare patients with severe comorbidities with patients with minor or no comorbidities.

Results

After PSM, no statistically significant differences regarding clinical characteristics were observed. We performed major resections in 26.4% of h‐ASA (ASA > 2) patients and 19.4% of l‐ASA (ASA≤2) patients, respectively (P = .322). Overall morbidity (Clavien‐Dindo≥1) was observed more frequently in the h‐ASA group (h‐ASA: 25.0% vs. l‐ASA: 8.3%; P = .007) while analysis of major morbidity (Clavien‐Dindo≥3b) showed a non‐significant tendency for more complications in h‐ASA patients (h‐ASA: 8.3% vs. l‐ASA: 1.4%; P = .053). A subgroup analysis identified major resection (HR = 5.05; P = .006) as an independent risk factor for the occurrence of any postoperative complication and chronic kidney disease (HR = 22.59; P = .030) and liver fibrosis (HR = 30.16; P = .031) as risk factors for the occurrence of major complications in h‐ASA patients.

Conclusion

LH in patients with severe systemic comorbidities shows a strong tendency towards an increased rate of major complications. Careful patient selection with respect to the planned extent of resection and the presence of chronic kidney disease and liver fibrosis should be performed to improve perioperative results.
Assessment of intellectual impairment, health‐related quality of life, and behavioral phenotype in patients with neurotransmitter related disorders: Data from the iNTD registry
Authors: Keller Mareike , Brennenstuhl Heiko , Kuseyri Hübschmann Oya , Manti Filippo , Julia Palacios Natalia Alexandra , Friedman Jennifer , Yıldız Yılmaz , Koht Jeanette Aimee , Wong Suet‐Na , Zafeiriou Dimitrios I. , López‐Laso Eduardo , Pons Roser , Kulhánek Jan , Jeltsch Kathrin , Serrano‐Lomelin Jesus , Garbade Sven F. , Opladen Thomas , Goez Helly ,   International Working Group on Neurotransmitter related Disorders (iNTD), Burlina Alberto , Cortès‐Saladelafont Elisenda , Fernández Ramos Joaquín Alejandro , García‐Cazorla Angeles , Hoffmann Georg F. , Kiat Hong Stacey Tay , Honzík Tomáš , Kavecan Ivana , Kurian Manju A. , Leuzzi Vincenzo , Lücke Thomas , Manzoni Francesca , Mastrangelo Mario , Mercimek‐Andrews Saadet , Mir Pablo , Oppebøen Mari , Pearson Toni S. , Sivri H. Serap , Steel Dora , Stevanović Galina , Fung Cheuk‐Wing
Published: July 2021

Inherited disorders of neurotransmitter metabolism are a group of rare diseases, which are caused by impaired synthesis, transport, or degradation of neurotransmitters or cofactors and result in various degrees of delayed or impaired psychomotor development. To assess the effect of neurotransmitter deficiencies on intelligence, quality of life, and behavior, the data of 148 patients in the registry of the International Working Group on Neurotransmitter Related Disorders (iNTD) was evaluated using results from standardized age‐adjusted tests and questionnaires. Patients with a primary disorder of monoamine metabolism had lower IQ scores (mean IQ 58, range 40‐100) within the range of cognitive impairment (<70) compared to patients with a BH4 deficiency (mean IQ 84, range 40‐129). Short attention span and distractibility were most frequently mentioned by parents, while patients reported most frequently anxiety and distractibility when asked for behavioral traits. In individuals with succinic semialdehyde dehydrogenase deficiency, self‐stimulatory behaviors were commonly reported by parents, whereas in patients with dopamine transporter deficiency, DNAJC12 deficiency, and monoamine oxidase A deficiency, self‐injurious or mutilating behaviors have commonly been observed. Phobic fears were increased in patients with 6‐pyruvoyltetrahydropterin synthase deficiency, while individuals with sepiapterin reductase deficiency frequently experienced communication and sleep difficulties. Patients with BH4 deficiencies achieved significantly higher quality of life as compared to other groups. This analysis of the iNTD registry data highlights: (a) difference in IQ and subdomains of quality of life between BH4 deficiencies and primary neurotransmitter‐related disorders and (b) previously underreported behavioral traits.
Inflammation in Remote Myocardium and Left Ventricular Remodeling After Acute Myocardial Infarction: A Pilot Study Using T2 Mapping
Authors: Yang Meng‐xi , Shi Ke , Xu Hua‐yan , He Yong , Ma Min , Zhang Lu , Wang Jun‐long , Li Xue‐sheng , Fu Chuan , Li Hong , Zhou Bin , Zhou Xiao‐yue , Yang Zhi , Guo Ying‐kun , Yang Zhi‐gang
Published: July 2021

Background

The pathophysiological changes in the remote myocardium after acute myocardial infarction (MI) remains less understood.

Purpose

To assess the inflammation in the remote myocardium post‐MI and its association with left ventricular (LV) remodeling using T2 mapping.

Study type

Prospective.

Animal Model and Subjects

Twelve pigs at 3‐day post‐MI, 6 pigs at 3‐month post‐MI, 6 healthy pigs; 54 patients at 3‐day and 3‐month post‐MI, 31 healthy volunteers;

Field Strength/Sequence

A 3 T MRI/ steady‐state free‐precession sequence for T2 mapping (animals: 0, 30, and 55 msec; human: 0, 25, and 55 msec), phase‐sensitive inversion recovery gradient echo for late gadolinium enhancement (LGE), balanced steady free‐precession sequence for cine.

Assessment

Infarcted myocardium was defined on LGE, remote T2 was measured on T2 maps. LV remodeling was evaluated as LV end‐diastolic volume change index between two scans using cine. CD68 staining was conducted to detect monocyte/macrophage.

Statistical Tests

Student‐t test and one‐way ANOVA were used to compare remote T2 with normal controls. The association of remote T2 with LV remodeling was assessed using linear regression. P values of <0.05 were used to denote statistical significance.

Results

Compared with healthy pigs, remote T2 significantly increased from 3 days to 3 months post‐MI (31.43 ± 0.67 vs. 33.53 ± 1.15 vs. 36.43 ± 1.07 msec). CD68 staining demonstrated the inflammation in remote myocardium post‐MI but not in healthy pigs. Significant remote myocardial alterations in T2 were also observed in human group (40.51 ± 1.79 vs. 41.94 ± 1.14 vs. 42.52 ± 1.71 msec). In patients, the 3‐month remote T2 (β = 0.432) and remote T2 variation between two scans (β = 0.554) were both independently associated with LV remodeling.

Conclusion

T2 mapping could characterize the abnormalities in the remote myocardium post‐MI, which was potentially caused by the inflammatory response. Moreover, variations in remote T2 were associated with LV remodeling.

Evidence Level

1

Technical Efficacy

Stage 3
Connectome analysis of male world‐class gymnasts using probabilistic multishell, multitissue constrained spherical deconvolution tracking
Authors: Tomita Hiroyuki , Kamagata Koji , Andica Christina , Uchida Wataru , Fukuo Makoto , Waki Hidefumi , Sugano Hidenori , Tange Yuichi , Mitsuhashi Takumi , Lukies Matthew , Hagiwara Akifumi , Fujita Shohei , Wada Akihiko , Akashi Toshiaki , Murata Syo , Harada Mutsumi , Aoki Shigeki , Naito Hisashi
Published: July 2021

In athletes, long‐term intensive training has been shown to increase unparalleled athletic ability and might induce brain plasticity. We evaluated the structural connectome of world‐class gymnasts (WCGs), as mapped by diffusion‐weighted magnetic resonance imaging probabilistic tractography and a multishell, multitissue constrained spherical deconvolution method to increase the precision of tractography at the tissue interfaces. The connectome was mapped in 10 Japanese male WCGs and in 10 age‐matched male controls. Network‐based statistic identified subnetworks with increased connectivity density in WCGs, involving the sensorimotor, default mode, attentional, visual, and limbic areas. It also revealed a significant association between the structural connectivity of some brain structures with functions closely related to the gymnastic skills and the D‐score, which is used as an index of the gymnasts' specific physical abilities for each apparatus. Furthermore, graph theory analysis demonstrated the characteristics of brain anatomical topology in the WCGs. They displayed significantly increased global connectivity strength with decreased characteristic path length at the global level and higher nodal strength and degree in the sensorimotor, default mode, attention, and limbic/subcortical areas at the local level as compared with controls. Together, these findings extend the current understanding of neural mechanisms that distinguish WCGs from controls and suggest brain anatomical network plasticity in WCGs resulting from long‐term intensive training. Future studies should assess the contribution of genetic or early‐life environmental factors in the brain network organization of WCGs. Furthermore, the indices of brain topology (i.e., connection density and graph theory indices) could become markers for the objective evaluation of gymnastic performance.
Net‐mineralization of organic matter and greenhouse gas emissions from Quebracho tannin‐enriched manure applied to acidic and alkaline soils
Authors: Ingold Mariko , Wachendorf Christine , Buerkert Andreas
Published: July 2021

Background

Mitigation strategies to reduce greenhouse gas emissions, ammonia volatilization, and nitrate leaching from agriculture are important for the management of environmental pollution and climate change. Tannins, which are water‐soluble polyphenolic compounds, were found to reduce emissions in animal husbandry systems when supplemented to ruminant diets.

Aim

Two laboratory incubation experiments were conducted to investigate the effects of Quebracho tannin‐enriched manure on carbon (C) and nitrogen (N) mineralization processes, and greenhouse gas emissions from three different soils (sandy moderate acidic, sandy alkaline, and loamy alkaline).

Methods

In the two incubation experiments of 4 and 9 weeks, soil samples were analyzed for K2SO4 extractable C and N, NH4+ and NO3–, microbial biomass C, and pH. In the main experiment emissions of CO2, N2O, and NH3 were regularly monitored.

Results

Three days after manure application, the CO2 emissions of the three soils were reduced by 26%–37% and N2O by 80%–92% in tannin‐enriched manure treatments compared with tannin‐free manure. However, subsequent cumulative CO2 and N2O emissions were only reduced in the loamy alkaline soil applied with tannin‐enriched manure. Also, in the initial 4 weeks net‐mineralization after manure application was significantly lower in soils applied with tannin‐enriched manure, reflecting an immobilization of N compared with tannin‐free manure in the short term or an inhibition of the mineralization process by physicochemical complexation of proteins or inhibition of enzyme activities in the long term. In both experiments, NO3– was by 23%–95% lower in the three soils after 3–9 weeks compared with tannin‐free manure.

Conclusion

These results highlight the mitigation potential of tannin‐enriched manure on soil N leaching, and suggest that greenhouse gas emissions may be increased depending on soil properties.
Surgical telementoring: Feasibility, applicability, and how to
Authors: Gerardo Rodrigo , Lele Prachi , Sundaram Krithika , Ponsky Todd
Published: July 2021

Surgical training does not end at the conclusion of residency training. Expansions in medical technology and surgical technique have created a steep learning curve for the young attending surgeon. The emergence of intraoperative telementoring has allowed experienced surgeons to guide learners through complex surgical cases remotely with the assistance of streaming video technology. Here, we describe the basics of telementoring, financial and legal considerations, and recommend hardware specifications for optimal use.