bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Aerosol Embedded in Shallow Cumulus Cloud Fields on the Surface Solar Irradiance
Authors: Gristey Jake J. , Feingold Graham , Schmidt K. Sebastian , Chen Hong
Published: June 2022

Ubiquitous shallow cumulus clouds are associated with complex variability in surface solar irradiance (SSI). Aerosol embedded in the cloud field typically has a much smaller overall radiative effect, but can significantly perturb the shape of the SSI probability density function (PDF). These perturbations have important implications for several applications that utilize SSI, but are poorly quantified and are the subject of this study. Multiple cases of shallow cumulus cloud fields with embedded aerosol are simulated at the Southern Great Plains Atmospheric Observatory using large eddy simulation (LES). The LES‐derived cloud and aerosol fields are then ingested into Monte Carlo three‐dimensional (3D) radiative transfer to simulate SSI. We find a variety of perturbations to the SSI PDF that depend on aerosol presence and optical properties. The processes leading to these perturbations include extinction of the direct beam that often increases from the clear‐sky region toward cloud edge due to aerosol hygroscopic growth, and scattering of radiation by aerosol into cloud shadows. The ability to predict the SSI PDF in the presence of aerosol is assessed by adding three representative aerosol optical properties into an existing machine learning framework. We show that machine learning accurately predicts the SSI PDF across a wide range of conditions with negligible computational expense. Importance metrics reveal the relatively high influence of aerosol optical properties in making the predictions. These new findings highlight the important role that aerosol plays in SSI variability for highly 3D cloud‐aerosol environments and provides a computationally efficient route forward for its simulation.
Molecular detection of bacterial contamination in plasma using magnetic-based enrichment
Authors: Lee Jinyeop , Abafogi Abdurhaman Teyib , Oh Sujin , Chang Ho Eun , Tepeng Wu , Lee Daekyu , Park Sungsu , Park Kyoung Un , Hong Yun Ji
Published: June 2022

Bacterial contamination of blood products is a major problem in transfusion medicine, in terms of both morbidity and mortality. Platelets (PLTs) are stored at room temperature (under constant agitation) for more than 5 days, and bacteria can thus grow significantly from a low level to high titers. However, conventional methods like blood culture and lateral flow assay have disadvantages such as long detection time, low sensitivity, and the need for a large volume of blood components. We used real-time polymerase chain reaction (PCR) assays with antibiotic-conjugated magnetic nanobeads (MNBs) to detect enriched Gram-positive and -negative bacteria. The MNBs were coated with polyethylene glycol (PEG) to prevent aggregation by blood components. Over 80% of all bacteria were captured by the MNBs, and the levels of detection were 101 colony forming unit [CFU]/mL and 102 CFU/mL for Gram-positive and -negative bacteria, respectively. The detection time is < 3 h using only small volumes of blood components. Thus, compared to conventional methods, real-time PCR using MNBs allows for rapid detection with high sensitivity using only a small volume of blood components.
Social networks respond to a disease challenge in calves
Authors: Burke Katharine C. , do Nascimento-Emond Sarah , Hixson Catherine L. , Miller-Cushon Emily K.
Published: June 2022

Changes in network position and behavioral interactions have been linked with infectious disease in social animals. Here, we investigate the effects of an experimental disease challenge on social network centrality of group-housed Holstein bull dairy calves. Within group-housed pens (6/group) calves were randomly assigned to either a previously developed challenge model, involving inoculation with Mannheimia haemolytia (n = 12 calves; 3 calves/group) or a control involving only saline (n = 12 calves; 3 calves/group). Continuous behavioral data were recorded from video on pre-treatment baseline day and for 24 h following inoculation to describe social lying frequency and duration and all active social contact between calves. Mixed-model analysis revealed that changes in network position were related to the challenge. Compared to controls, challenged calves had reduced centrality and connectedness, baseline to challenge day. On challenge day, challenged calves were less central in the directed social contact networks (lower degree, strength and eigenvector centrality), and initiated contact (higher out-degree) with more penmates, compared to healthy calves. This finding suggests that giving rather than receiving affiliative social contact may be more beneficial for challenged calves. This is the first study demonstrating that changes in social network position coincide with an experimental challenge of a respiratory pathogen in calves.
A combination of scanning electron microscopy and broad argon ion beam milling provides intact structure of secondary tissues in woody plants
Authors: Hatano Tomohiro , Nakaba Satoshi , Horikawa Yoshiki , Funada Ryo
Published: June 2022

The secondary tissues of woody plants consist of fragile cells and rigid cell walls. However, the structures are easily damaged during mechanical cross-sectioning for electron microscopy analysis. Broad argon ion beam (BIB) milling is commonly employed for scanning electron microscopy (SEM) of hard materials to generate a large and distortion-free cross-section. However, BIB milling has rarely been used in plant science. In the present study, SEM combined with BIB milling was validated as an accurate tool for structural observation of secondary woody tissues of two samples, living pine (Pinus densiflora) and high-density oak wood (Quercus phillyraeoides), and compared with classical microtome cross-sectioning. The BIB milling method does not require epoxy resin embedding because of prior chemical fixation and critical point drying of the sample, thus producing a three-dimensional image. The results showed that xylem structures were well-preserved in their natural state in the BIB-milled cross-section compared with the microtome cross-section. The observations using SEM combined with BIB milling were useful for wide-area imaging of both hard and soft plant tissues, which are difficult to observe with transmitted electron microscopy because it is difficult to obtain sections of such tissues, particularly those of fragile reaction woods.
Genetic architecture of band neutrophil fraction in Iceland
Authors: Oskarsson Gudjon R. , Magnusson Magnus K. , Oddsson Asmundur , Jensson Brynjar O. , Fridriksdottir Run , Arnadottir Gudny A. , Katrinardottir Hildigunnur , Rognvaldsson Solvi , Halldorsson Gisli H. , Sveinbjornsson Gardar , Ivarsdottir Erna V. , Stefansdottir Lilja , Ferkingstad Egil , Norland Kristjan , Tragante Vinicius , Saemundsdottir Jona , Jonasdottir Aslaug , Jonasdottir Adalbjorg , Sigurjonsdottir Svanhvit , Petursdottir Karen O. , Davidsson Olafur B. , Rafnar Thorunn , Holm Hilma , Olafsson Isleifur , Onundarson Pall T. , Vidarsson Brynjar , Sigurdardottir Olof , Masson Gisli , Gudbjartsson Daniel F. , Jonsdottir Ingileif , Norddahl Gudmundur L. , Thorsteinsdottir Unnur , Sulem Patrick , Stefansson Kari
Published: June 2022

The characteristic lobulated nuclear morphology of granulocytes is partially determined by composition of nuclear envelope proteins. Abnormal nuclear morphology is primarily observed as an increased number of hypolobulated immature neutrophils, called band cells, during infection or in rare envelopathies like Pelger-Huët anomaly. To search for sequence variants affecting nuclear morphology of granulocytes, we performed a genome-wide association study using band neutrophil fraction from 88,101 Icelanders. We describe 13 sequence variants affecting band neutrophil fraction at nine loci. Five of the variants are at the Lamin B receptor (LBR) locus, encoding an inner nuclear membrane protein. Mutations in LBR are linked to Pelger-Huët anomaly. In addition, we identify cosegregation of a rare stop-gain sequence variant in LBR and Pelger Huët anomaly in an Icelandic eight generation pedigree, initially reported in 1963. Two of the other loci include genes which, like LBR, play a role in the nuclear membrane function and integrity. These GWAS results highlight the role proteins of the inner nuclear membrane have as important for neutrophil nuclear morphology.
Correction: A smartphone-based three-in-one biosensor for co-detection of SARS-CoV-2 viral RNA, antigen and antibody
Authors: Dou Yanzhi , Su Jing , Chen Shixing , Li Tie , Wang Lihua , Ding Xianting , Song Shiping , Fan Chunhai
Published: June 2022

Correction for ‘A smartphone-based three-in-one biosensor for co-detection of SARS-CoV-2 viral RNA, antigen and antibody’ by Yanzhi Dou et al., Chem. Commun., 2022, DOI: https://doi.org/10.1039/d2cc01297a.
Visible-light-induced Smiles rearrangement without release of SO2: rapid access to alkyl sulfonyl derivatives
Authors: Cao Yunpeng , Wang Xinmou , Jiao Haoran , Song Hongjian , Liu Yuxiu , Wang Qingmin
Published: June 2022

Conventional visible-light-induced Smiles rearrangements generate C, N, or O radicals and release SO2.
Evaluation of blood and synthetic matrix-matched calibrations using manual and inline sample preparation methods
Authors: Quarles C. Derrick , Bohlim Nick , Wiederin Kevin , Saetveit Nathan , Sullivan Patrick
Published: June 2022

Validation and performance for automated manual and inline sample preparation and analysis methods for whole blood samples.
A total consumption infrared heated sample introduction system for nanoparticle measurement using single particle inductively coupled plasma mass spectrometry
Authors: Zhou Zichao , Al Hejami Ahmed , Burgener Mirah J. , Burgener John , Beauchemin Diane
Published: June 2022

A compact infrared-heated sample introduction system provides essentially 100% transport efficiency for single particle inductively coupled plasma mass spectrometry.
A reliable calibration method for accurate determination of major and trace elements in fluorapatite by LA-ICP-MS without an internal standard
Authors: Zhang Hao-Xiang , Jiang Shao-Yong , Su Hui-Min , Liu Si-Qi , Li Wen-Tian
Published: June 2022

During in situ determination of major and trace element concentrations of minerals by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), an internal standard is needed.
In vivo enzymatic digestion of HRV 3C protease cleavage sites-containing proteins produced in a silkworm-baculovirus expression system
Authors: Xu Jian , Nakanishi Takafumi , Kato Tatsuya , Park Enoch Y.
Published: June 2022

Baculovirus expression vector system (BEVS) has been recognized as a potent protein expression system in engineering valuable enzymes and vaccines. Various fusion tags facilitate protein purification, leaving the potential risk to influence the target protein's biological activity negatively. It is of great interest to consider removing the additional tags using site-specific proteases, such as human rhinoviruses (HRV) 3C protease. The current study validated the cleavage activity of 3C protease in Escherichia coli and silkworm-BEVS systems by mixing the cell or fat body lysates of 3C protein and 3C site containing target protein in vitro. Further verification has been performed in the fat body lysate from co-expression of both constructs, showing remarkable cleavage efficiency in vivo silkworm larvae. We also achieved the glutathione-S-transferase (GST) tag-cleaved product of the VP15 protein from the White spot syndrome virus after purification, suggesting that we successfully established a coinfection-based recognition-and-reaction BEVS platform for the tag-free protein engineering.
Innovative separation model for boron removal from silicon during slag refining based on ion and molecule coexistence theory
Authors: Li Shijian , Qian Guoyu , Sun Yiwei , Pang Sheng , Wang Dong , Wang Zhi
Published: June 2022

How to reduce boron concentration to an extremely low level has become a major obstacle during silicon waste recycling. As a simple and efficient method of removing impurities, slag refining plays an increasingly important role for industrial silicon waste recovery. The deboration ability of slag is usually evaluated by boron distribution ratio LB. However, the development of a separation prediction model is challenged by the limitations on the recognition of impurity structure in slag and complexity of slag-silicon reactions. Herein, a novel thermodynamic model for predicting boron distribution ratio between CaO-SiO2 based slags and molten silicon has been developed based on ion and molecule coexistence theory (IMCT), i.e., IMCT-LB model. The reaction abilities of structural units are represented by the calculated mass action concentration. The predictive boron distribution ratio between CaO-SiO2, CaO-Al2O3-SiO2, CaF2-CaO-SiO2 slags and silicon correspond well with experimental data, reflecting the reasonability of IMCT-LB model. According to IMCT, deboration reactions between slags and silicon can be represented by ion couples (Ca2+ + O2–), simple molecule Al2O3 with SiO2 to form eight deboration products as B2O3, 3CaO · B2O3, 2CaO · B2O3, CaO · B2O3, CaO · 2B2O3, 2Al2O3 · B2O3, 9Al2O3 · B2O3, CaO · 2SiO2 · B2O3. With the developed IMCT-LB model, the respective boron distribution ratio LB,i of the eight deboration products can be determined quantitatively. Furthermore, the effect of temperature, mass ratio of CaO to SiO2 (%CaO/%SiO2), Al2O3 and CaF2 content of CaO-SiO2 based slags on LB are fully discussed.
Amidation of α-Amino Acids Using Dichloro(methyl)(3,3,3-trifluoropropyl)silane and Imidazole without Conventional Protection and Deprotection of α-Amino Group
Authors: Nobuta Tomoya , Morishita Honoka , Suto Yutaka , Yamagiwa Noriyuki
Published: June 2022

Amidation of amino acids using dichloro(methyl)(3,3,3-trifluoropropyl)silane (MTFPSCl2) and imidazole is described. MTFPSCl2 activates the carboxy group and protects the α-amino group of amino acids. The amidation proceeded with 19 amino acids and 19 amines, including α-branched amines and anilines; the corresponding amino acid amides were synthesized in good-to-high yields (up to 96%) with low-to-no racemization.
Listening Effort in Hearing Aid Users: Is It Related to Hearing Aid Use and Satisfaction?
Authors: Kiliç Samet , Yiğit Öznur , Türkyilmaz Meral D.
Published: June 2022

Abstract Background Listening effort is primarily reflective of real-world performance. Therefore, it is crucial to evaluate the listening effort to predict the performance of hearing aid (HA) users in their daily lives. Purpose This study aimed
to investigate the relationship between listening effort, daily HA use time, and HA satisfaction. Research Design This is a cross-sectional study. Study Sample Thirty-three bilateral behind-the-ear HA users (17 females and 16 males) between 19 and 37 years were
participated. All participants had bilateral, symmetric, moderate sensorineural hearing loss and at least 6 months of experience using HAs. The pure-tone average thresholds (PTA) of the participants' left and right ears were 55.34 ± 4.38 and 54.85 ± 5.05,
respectively. Data Collection and Analysis First, daily HA use times of the last 30 days were derived from data logging. Second, participants were asked to fill in the Satisfaction with Amplification in Daily Life Scale questionnaire (SADL). Lastly, participants performed the
dual-task paradigm to evaluate listening effort. The dual-task paradigm consisted of a primary speech recognition task that included three different individualized signal-to-noise ratio (SNR) conditions, that is, SNR100, SNR80, and SNR50, which the participant could understand 100, 80, and
50% of the speech, respectively. The secondary task was a visual reaction time task that required participants to press the key in response to a visual probe (an image of a white or red rectangle). Multiple linear regression analyses were used to model the effect of factors (daily HA use time
and HA satisfaction) on reaction times (RT) of each three individualized SNR sessions. Results Mean daily HA use time of the participants was 5.72 ± 4.14 hours. Mean RTs of SNR50, SNR80, and SNR100 conditions were 1,050.61 ± 286.49,
893.33 ± 274.79, and 815.45 ± 233.22 ms, respectively. Multiple linear regression analyses showed that daily HA use time and HA satisfaction are significantly related to listening effort in all SNR conditions. For SNR80 condition; F (2,30) = 47.699,
p < 0.001, with an adjusted R 2 of 0.745. Conclusion As far as we know, this study is the first to demonstrate a strong link between listening effort, daily HA use time, and HA satisfaction. Evaluating listening effort following the
HA fitting session may provide preliminary information about the treatment success of HA.
Endoscopic Options for Moderate COPD, Chronic Bronchitis, and Uncontrolled Asthma
Authors: Herth Felix J.F. , Kontogianni Konstantina , Brock Judith
Published: June 2022

Until now, interventional therapies for patients with chronic obstructive pulmonary disease have been available in the form of lung volume reduction procedures as end-stage options. Currently, the range of indications is expanding to include earlier stages of the diseases. Lung denervation is available for moderate COPD, and patients with chronic bronchitis are being evaluated for endoscopic goblet cell ablation. Rheoplasty, metered spray cryo technique, and Karakoca resector balloon are used for this indication. But also, for patients with severe uncontrolled asthma, several techniques are available today. In addition to thermoplasty as a long-proven procedure, new and currently under investigation is the targeted lung denervation.

Most of these techniques are currently being tested in large pivotal trials and it will soon become clear in which phenotype which technique will be used in the different forms and stages of obstructive diseases. The current paper presents the techniques and the currently available literature.
Isolated Headache as a Symptom of the Acute Coronary Syndrome in a Case following Myocardial Revascularization
Authors: Nanda Chinmaya , Mehta Yatin
Published: June 2022

Retrosternal chest pain is the classical symptom of acute coronary syndrome (ACS). ACS sometimes presents with atypical symptoms and very rarely as headache as the only symptom. We present here a case where a patient who had undergone coronary artery bypass grafting presented with headache and on evaluation found to have complete occlusion of right coronary artery.
Infections Acquired During Venoarterial Extracorporeal Membrane Oxygenation Postcardiac Surgery in Children: A Retrospective Observational Study
Authors: Yagani Seshagiribabu , Singh Sarvesh Pal , Sahu Manoj Kumar , Choudhary Shiv Kumar , Chowdhury Ujjwal Kumar , Hote Milind Padmakar , Singh Ummed , Reddy Pradeep Ramakrishna , Panday Shivam
Published: June 2022

Introduction Extracorporeal membrane oxygenation (ECMO) is increasingly being used in refractory cardiac and pulmonary dysfunction as a rescue modality. The common indications for establishing venoarterial ECMO (VA-ECMO) support in children postcardiac surgery are failure to wean from cardiopulmonary bypass (CPB), postcardiotomy cardiogenic shock (PCCS), refractory pulmonary arterial hypertension, and as a bridge to recovery or transplant. The survival rate of children on VA-ECMO support is 45%. The most frequently encountered complications during VA-ECMO are bleeding, thrombosis, acute kidney injury, and infections. Among those, infections acquired during VA-ECMO lead to high morbidity and mortality. Hence, this study aimed to determine infection rates, causal microorganisms, and mortality risk factors in children developing an infection during VA-ECMO therapy.

Methods This retrospective observational study was conducted on 106 children under 14 years of age who underwent elective or emergent cardiac surgery (between 2016 and 2020) and required VA-ECMO support. Medical records were reviewed to collect the targeted variables and analyzed.

Results Out of 106 children, 49 (46.23%) acquired infections representing a prevalence of 46.23% and an infection rate of 186.4 episodes per 1,000 ECMO days. Prevalence and acquired infection rate/1,000 ECMO days were higher in the nonsurvivor group than in the survivor group (26.42 vs.19.81%) and (215.07 vs. 157.49), respectively. The bloodstream infection (BSI) and catheter-associated urinary tract infection (CAUTI) episodes were 53.04 and 68.19 per 1,000 ECMO days, and the ventilator-associated pneumonia (VAP) rate was 44.50 per 1,000 ventilator days. The mean preoperative admission duration, aortic cross-clamping duration, CPB duration (minutes), and vasoactive-inotropic score were higher in the nonsurviving children (p < 0.001). Similarly, prolonged mean ECMO duration was also found in the nonsurvivor group compared with the survivor group (p = 0.03).

Conclusion In our study, the prevalence of acquired infection during VA-ECMO was 46.23%. The incidence of BSI, CAUTI, and VAP per 1,000 ECMO days was higher in the nonsurvivor group than in survivors. Acinetobacter baumannii was the most common cultured gram-negative organism in VAP and BSI, with 67.65% Acinetobacter spp. resistant to carbapenems. CAUTI was predominately due to Candida species during VA-ECMO.
Dysglycemia in ICU Patients
Authors: Joshi Anshu , Mehta Yatin
Published: June 2022

Dysglycemia has emerged as a very common challenge in critically ill patients, especially with regard to current coronavirus disease 2019 pandemic. Prediabetes, poorly controlled diabetes, pharmaceutical intervention in intensive care unit (ICU) with glucocorticoids, catecholamines and other medicines, and stress response all contribute to dysglycemia in critically ill patients. Early identification and management are the key to prevent further complications. Patient prognosis in terms of clinical outcome, length of ICU stay, and in-hospital morbidity/mortality are adversely affected by patient's dysglycemic status. Apart from hyperglycemia, the other three important pillars of dysglycemia are discussed in this article. Synopsis of early intervention have been captured from India-specific practice guidelines. Important landmark trials have also been captured in this article to provide a clarity on certain aspects of managing dysglycemia in ICUs. Hence, this review article is an attempt to bring forth the salient aspects in diagnosing and managing dysglycemia in critical care settings.
Risk of Developing Acute Kidney Injury on the VA ECLS Circuit in Patients with Acute Decompensated Heart Failure
Authors: Reaz Shams , Loyaga-Rendon Renzo , Dickinson Michael G. , Lee Sangjin , Fitch Stephen J. , Marco Greg , Boeve Theodore , Langholz David E. , Kelty Catherine , Shrestha Nabin Manandhar , Leacche Marzia , Jovinge Stefan
Published: June 2022

Aims Venoarterial extracorporeal life support (VA ECLS) is a life-saving treatment with a high risk of mortality. Appropriate patient selection is critical for optimal patient outcomes. Acute kidney injury (AKI) is a common risk among VA ECLS patients, and more information is needed to understand how AKI affects the mortality risk of these patients. To do this, we examined acute decompensated heart failure (ADHF) patients supported by VA ECLS and compared their risk of developing AKI to a background population. VA ECLS has become an increasingly important tool to bridge or recover patients with severe ADHF as the primary indication of VA ECLS.

Methods and Results All VA ECLS patients from a single center were included. ADHF patients supported by VA ECLS were compared with the remaining VA ECLS cohort. CATEGORICAL comparisons were made between groups using chi-squared and Fisher's exact tests. A survival analysis was conducted to determine freedom from AKI between the two groups. Predictor variables were tested by multiple logistic regression. Of the 255 patients included in this study, 110 had ADHF as their primary indication for VA ECLS and 145 patients had other VA ECLS indications. The survival analysis showed that patients with ADHF had a decreased risk of developing AKI on the VA ECLS circuit. Multiple logistic regression revealed no predictors in AKI development between groups and no difference in 30-day mortality was observed.

Conclusion Patients supported by VA ECLS are at high risk of mortality and complications. This research demonstrated that medically complex ADHF patients had less chance of developing AKI when compared with other patients supported by VA ECLS. Future research is needed to investigate potential protective mechanisms of VA ECLS support.
Unlocking the potential of microcrystal electron diffraction
Authors: Martynowycz Michael W. , Gonen Tamir
Published: June 2022

Structural biologists are using cryogenic electron microscopy to resolve atomic-scale structures of proteins from nanocrystals.
Correlated grammaticalization
Authors: Goldstein David
Published: June 2022

Grammaticalization is characterized by robust directional asymmetries (e.g.,Kuteva et al. 2019). For instance, body-part nominals develop into spatial adpositions, minimizers develop into negation markers and subject pronouns become agreement markers. Changes in the opposite direction are either rare or unattested (Garrett 2012: 52). Such robust cross-linguistic asymmetries have led some scholars to reify grammaticalization trajectories as universal mechanistic forces (Heath 1998: 729). One consequence of such a view is that the ambient morphosyntax of a language has little or even no relevance for grammaticalization. This paper uses Bayesian phylogenetic methods to demonstrate the critical role that pre-existing morphosyntax can play in grammaticalization. The empirical basis for this claim is the grammaticalization of definite and indefinite articles in the history of Indo-European: indefinite articles developed at a faster rate among languages in which a definite article had already emerged compared to those lacking a definite article. The two changes are thus correlated. The results of this case study suggest that there is much more to be learned about when and why grammaticalization occurs by investigating its relationship to the pre-existing linguistic system (cf.Reinöhl and Himmelmann 2017: 381).
On negative spheres in elliptic surfaces
Authors: Stipsicz András , Szabó Zoltán
Published: June 2022

Using elliptic fibrations with specific singular fibers, we find spheres with very negative self-intersections in elliptic surfaces and in their blow-ups.
Primary or secondary wound healing of the pin sites after removal of the external fixator: A monocenter prospective randomized controlled trial
Authors: Roth F , Hoepelman R , van de Wall B , Cagienard F , Babst R , Beeres F
Published: June 2022

Objective

The aim of this monocentre randomized controlled trial was to compare primary wound closure using a single button suture to secondary wound healing of pin sites after removal of the external fixator.

Methods

This non-inferiority trial included all patients who were treated with an external fixator. The primary outcome was infection. Secondary outcomes included all other complications, time to wound healing (in weeks), patients most satisfactory pin site, Visual Analogue Scale (VAS) for pain and the Vancouver Scar Scale (VSS) measured at every 2, 6, 12, 24 and 52 weeks. The most proximal pin site was randomly allocated (1:1) to either primary closure or secondary wound healing, while the following pin sites were treated alternately. Physicians at follow-up were blinded to the closure technique.

Results

A total of 70 patient, providing 241 pin sites were included between 1st January 2019 and 1st March 2020. One-hundred-twenty-three pin sites were treated with primary closure and 118 with secondary wound healing. Median age was 55 (46–67), 44% was male and median duration of the external fixator was 6 days (4–8).There was no significant difference in pin site infections (2% in the primary closure group versus 0% in the secondary healing group). Wound healing was significantly faster in the primary closure group (median 2 vs. 6 weeks, p=0.013). Although not statistically significant, patients seemed more satisfied with the primary closed pin sites (55%). The Vancouver Scar scale showed no differences between groups.

Conclusion

Primary closure of external pin sites does not result in higher infection rate than secondary wound healing and pin sites healed significantly faster after primary closure. Primary closure, therefore, should be the preferred method.
Prognostic factors in patients with acute mesenteric ischemia – a novel tool for determining patient outcomes
Authors: Sinz S , Schneider M A , Graber S D , Alkadhi H , Rickenbacher A , Turina M
Published: June 2022

Objective

Acute mesenteric ischemia (MI) is a devastating disease with poor prognosis. Due to the multitude of underlying factors and broad clinical presentation, prediction of outcomes remains poor. Here, we aimed to identify factors governing survival in MI and develop a novel prognostic tool.

Methods

The present study is a monocentric retrospective analysis of patients with suspected MI undergoing imaging between January 2014 and December 2019. Primary endpoint was identification of factors influencing survival in patients undergoing surgery for confirmed MI, secondary endpoint was the development of a predictive nomogram to aid in determination of patient prognosis.

Results

539 patients underwent CT imaging for suspected MI, 216 of which had radiological indication of MI and 137 of those had subsequently confirmed MI. Factors associated with confirmed ischemia were increasing age, nausea/vomiting, history of peripheral arterial disease and presence of pneumatosis intestinalis and dilated bowel loops.

125 patients underwent surgery, 58 of which survived, and 67 died (median 9 days after diagnosis, IQR: 22). Baseline characteristics, including time from diagnosis to surgery were not different among patients, and outcomes were not affected by the presence of a surgical senior consultant or daytime of the operation. A minimally invasive approach was attempted more often in survivors (25.9% vs. 10.4%, p=0.024), however, in all but 1 patient (1.7%) conversion to open surgery was performed following detection of ischemia.

Increasing age and ASA score, type 2 diabetes, decreased haemoglobin and pH, increased creatinine, radiological atherosclerosis, vascular occlusion (versus non-occlusive MI) and affection of the colon (compared to small bowel ischemia only) were independently associated with impaired survival. Based on a multivariate model, we developed a nomogram for survival prediction, which showed adequate power upon internal validation (C-index = 0.738, Figure 1).

Conclusion

Acute MI remains a condition with high mortality. Here, we identified factors affecting survival after MI, namely colonic involvement, vascular co-morbidities and increasing age. Minimally invasive surgical approaches have not yet gained widespread acceptance in treatment of confirmed MI. Our novel nomogram might prove helpful in outcome prediction of patients with MI.
Attitudes of primary care physicians towards bariatric surgery in Switzerland – a free-word association networks analysis
Authors: Müller V , Gero D , File B , Widmer J , Thalheimer A , Bueter M
Published: June 2022

Objective

Primary care physicians (PCP) have a major responsibility in identifying patients with obesity eligible for bariatric surgery (BS). The aim was to explore PCPs’ attitudes towards BS in order to map potential barriers of referral.

Methods

3526 PCPs in Switzerland were invited to participate in an online survey. PCPs were asked to write the first 5 words coming to their mind about the term “bariatric surgery”. Additionally, they had to pick 2 emotions that best described each provided association. Demographic data and obesity-related referral patterns were collected. Cognitive representation network was constructed based on co-occurrence of associations, using validated data-driven methodology.

Results

216 PCPs completed the study. Respondents were aged 55±9.8 years, had an equal gender distribution and practiced mainly in urban setting (Table 1). The majority of PCPs refer either often (31%) or sometimes (41%) patients for BS, while 7% never refer patients to BS, even if eligibility criteria are met. The PCPs’ overall satisfaction with BS was high (88.5%)(Fig. 1). PCPs could be categorized in 3 subgroups based on their cognitive representation of BS: a) indication-focused (most frequent associations: “obesity”, ”diabetes”/most frequent emotion: “worrying”), b) treatment-focused (“gastric bypass”, “weight loss”/“interested”), and c) risk vs. benefit-focused (“complications”, “challenging follow-up”, “success”/“alert”) (Fig. 2&3). There were no relevant demographic or practice related differences between PCPs in the 3 cognitive modules. PCPs with a treatment-focused mindset had a significantly better knowledge of current guidelines on indications of BS (χ2=17.1, P=0.029) and referred in average 5 patients/year, x2 more than PCPs belonging to the other cognitive modules.

Conclusion

PCPs in Switzerland approve the efficacy of BS, but show reservation to refer eligible patients systematically. PCPs think about BS along 3 cognitive schemes, and the treatment-focused attitude was coupled with the highest willingness to refer eligible patients for BS. Confident knowledge of current indications of BS was the only significant factor that distinguished PCPs with a treatment-focused attitude. Strengthening the collaboration in therapeutic decision-making between PCPs and BS centers has the potential to improve access to optimal care for patients with obesity.
Improved outcomes in proximal gastric bypass surgery following the transition from a conventional circular stapling to an augmented linear stapling protocol
Authors: Römer N , Hauswirth F , Teuber H , Teuben M P J , Neff T A , Müller M K
Published: June 2022

Objective

Bariatric techniques for bypass surgery evolve constantly. Switching from one well-established protocol to another in a running surgical teaching program is challenging. We analyzed clinical outcomes, safety and costs at a single bariatric center transitioning from circular to an augmented linear bypass protocol.

Methods

Between 2011 and 2018, 454 patients were included in this retrospective study. The circular bypass protocol (CIRC; n=177) was primarily used between 2011–2012. Between 2013–2015 the transition occurred. Thereafter, the augmented linear protocol (aLIN; n=277) was primarily utilized.

Results

Overall, mean preoperative BMI dropped from 42.2 kg/m2 to 29.6 kg/m2 after 5 years with no difference between groups. Operation times were significantly shorter in the aLIN-group, compared with CIRC-patients at 108 (±32) vs. 120 (±34) minutes (P<0.001), respectively. The reoperation rate was significantly higher in the CIRC vs. aLIN group at n=65 (36%) vs. n=35 (13%; P<0.001), respectively. Specifically, revision due to internal hernia occurred much more frequently in the CIRC-group, n=36 (20%) vs. n=12 (4%; P<0.001). Moreover, reoperation due to gastrojejunostomy-leakage and endoscopic dilatation for anastomotic stenosis was more common in the CIRC vs. aLIN group (P<0.001). Adjusted overall cost per case was lower in aLIN-patients at 15,403 (±7,848) vs. CIRC-patients at 18,525 (±7,850) Swiss Francs (P<0.001). Overall profit was 2,555 ± 4,768 vs. 1,455 ± 5,638 Swiss Francs in the aLIN vs. CIRC-group, respectively (P=0.026).

Conclusion

This study showed improved clinical outcomes while also secondarily improving financial performance after a gradual transition from a circular stapling protocol to an augmented linear stapling protocol in proximal gastric bypass surgery. The technical transition in this study proves, that if a new technique is superior in terms of safety and postoperative morbidity, it will also be financially beneficial.
Outcome of revisional procedures up to 14 years after sleeve gastrectomy: A single-center experience
Authors: Dirnberger A S , Süsstrunk J , Schneider R , Slawik M , Peterli R , Kraljević M
Published: June 2022

Objective

In the long-term, laparoscopic sleeve gastrectomy (SG) may be associated with insufficient weight loss, weight regain, development of gastroesophageal reflux disease (GERD) as well as persistence or relapse of comorbidities. The study's objective was to present results regarding weight loss, evolution of comorbidities and reoperation rate of patients who underwent a revisional bariatric procedure after SG.

Methods

Retrospective single-center analysis of a prospective database on patients who had a minimal follow-up of two years after conversion from SG to either a proximal Roux-en-Y gastric bypass (PRYGB), biliopancreatic diversion type duodenal switch (BPD/DS), long bilio-pancreatic limb-Roux-en-Y gastric bypass (LRYGB) or re-sleeve gastrectomy (RSG).

Results

Over a time period of 14 years, 549 SGs were performed. A total of 71 patients (13.0%) underwent a conversion from SG to PRYGB (n = 28, 39.4%), BPD/DS (n = 19, 26.8%), LRYGB (n = 17, 23.9%) and RSG (n = 7, 9.9%). Indications for the revisional procedures were GERD (33.8%), insufficient weight loss/weight regain (32.4%), a combination of both (31.0%) or stenosis/kinking of the sleeve (2.8%). The mean time from SG to revision was 5.2 ± 3.1 years and the mean pre-revisional body mass index (BMI) was 38.0 ± 7.5 kg/m2. The mean follow-up time after revision was 5.1 ± 3.1 years. The overall percentage of total weight loss (%TWL) was greatest after BPD/DS (36.6%) and LRYGB (32.9%) compared to RSG (20.0%; p = 0.04; p = 0.01). Patients with BPD/DS had significantly higher additional %TWL (26.2%) after conversion compared to PRYGB (15.6%, p = 0.04) and RSG (10.9%, p = 0.01). In case of GERD, reoperation led to a resolution of symptoms in 81.6% after RYGB. 19.7% of patients underwent an additional revisional procedure for internal herniation, chronic diarrhea after BDP/DS, common bile duct stones and weight regain.

Conclusion

In the event of insufficient weight loss/weight regain after SG, conversion to BPD/DS provides a significant post-revisional weight loss. RYGB leads to good symptom control in patients suffering from GERD.
Intracellular Proprotein convertase subtilisin/kexin type 9: Recruitment and regulatory role in mitochondrial architecture and bioenergetic
Authors: Gavini J , Leuenberger D , Yarahmadov T , Dommann N , Keogh A , Melin N , Tschan M , Nuoffer J-M , Hertig D , Zuber B , Odriozola A , Tombolini R , Chrétien M , Mbikay M , Candinas D , Stroka D
Published: June 2022

Objective

Circulating Proprotein convertase subtilisin/kexin type 9 (PCSK9) captured the scientific community's attention as powerful target to fight against high serum cholesterol and its associated adverse consequences. Despite the well-described role of PCSK9 in impairing the recycling of low-density lipoprotein receptor (LDLR) on hepatocytes, its intracellular importance in metabolism modulations remain largely unexplored. Here, we describe a novel intracellular function of PCSK9 in hepatocyte metabolism and in liver regeneration.

Methods

A surgical model of partial hepatectomy (PH) was used to induce liver cell proliferation and serological and histological lipo- and glyco-metabolic perturbations were investigated in PCSK9 knockout and wild-type mice before and after PH. Mitochondrial bioenergetic level, compartmental architecture as well as intracellular localization and function of PCSK9 were further analyzed in vitro on murine primary isolated hepatocytes and PCSK9 lentiviral knockdown human liver cancer cell lines.

Results

Loss of PCSK9 expression led to a basal higher mitochondrial bioenergetic status in hepatocytes, characterized by a profound remodeling of mitochondrial architecture. Livers from PCSK9 knockout mice displayed a diffuse oxidative stress and a significant upregulation of cellular detoxification and superoxide radicals removal genes induced by the activation of c-Jun N-terminal kinase (JNK) pathway before PH. PCSK9 deficient mice showed a primed compensatory hepatic hyperplasia after PH, accompanied by an earlier transient regeneration-associated steatosis due to a higher LDLR expression and cholesterol uptake, with an increased β-oxidation, gluconeogenesis and glycolysis rate. Tetramethylrhodamine ethyl ester staining of isolated hepatocytes and liver cancer PCSK9 knockdown clones revealed a significantly reduced mitochondrial membrane potential when compared to controls. Confocal live-cell imaging and proteins immunoprecipitation showed respectively a mitochondrial recruitment of PCSK9 in proliferating cells and its interaction with mitochondrial membrane carriers and chaperons.

Conclusion

Despite the role played by circulating PCSK9 in regulating systemic cholesterol levels, our data shed light on its intracellular impact on mitochondrial architecture, membrane polarization and related metabolic perturbations in compartmental bioenergetics.
Cell death in lung transplantation. The roles of apoptosis, necroptois, and pyroptosis
Authors: Lugrin J , Debonneville A , Ojanguren A , Hasenauer A , Parapanov R , Gonzalez M , Perentes J , Liaudet L , Krueger T
Published: June 2022

Objective

For patients with end stage lung disease, lung transplantation (Ltx) is the unique treatment option. Nevertheless, a large number of lung allografts fail, because of acute or chronic rejection. Innate immune responses following Ltx play a critical role in the development of primary graft dysfunction, and ultimately promote the development of chronic lung allograft dysfunction, leading to increased mortality after lung transplantation. Here, we focus on the mechanisms responsible for disruption of the cells membranes integrity, resulting in the release of Damage Associated Molecular Patterns (DAMPs) and activation of cell death pathways triggering cell injury in lungs with different preservation status.

Methods

Rat lungs were exposed to cold ischemia (CI group, n=9) or warm ischemia (WI group, n=9). In CI group, after Perfadex flushing, and hypothermic preservation (4 h) left lung was transplanted. In WI group, after 1 h of in situ WI, flashing and 3 h cold preservation the left lung was transplanted. Lung mechanics were determined during reperfusion. Recipients were sacrificed at 30, 60 and 120 min after Ltx. Bronchoalveolar lavage (BAL) was performed on the grafts to measure markers of cellular injury, and cytokines. Cell death markers were determined in graft tissue. Biological samples were kept at -80°C for additional analysis.

Results

Compared to CI, WI group displayed significantly decreased graft function associated with increased activation of pyroptotic cell death (NLRP3, caspase1, IL-1β) pathway, whereas apoptotic (caspas3 and caspase7) and necroptotic (RIP1, RIP3, MLKL) cell death pathways activation were similar in both groups. WI group showed more important cellular damage with DAMPs release (LDH, sRAGE, HMGB) and inflammation (CXCL1, IL1-β, IL-33).

Conclusion

Our results suggest that pyroptosis could play a critical role in the development of early graft dysfunction in lungs subjected to warm ischemia. Inhibition of pyroptotic pathway could be a strategy to improve damaged donor lungs.
Hypocortisolemia following unilateral adrenalectomy
Authors: Matter M , Mateev E , Sykiotis G , Demartines N
Published: June 2022

Objective

Unilateral adrenalectomy (UA) is the best option for unilateral functioning and non-functioning adrenal adenomas, localized primary or metastatic carcinomas. Post-operative hypocortisolemia (HC) in Cushing Syndrome is well known, but several studies reported HC after UA for other indications. A systematic full endocrine investigation for all adrenal mass is not systematic and dexamethasone suppression test (DST) is not recommended in non-Cushing functioning tumours. Double secretion (autonomous cortisol co-secretion) is a rare phenomenon. The purpose of the study was to review incidence of postoperative HC in a tertiary centre.

Methods

Retrospective study (2012–2020) looking for hypocortisolemia after UA in patients operated for Cushing Syndrome and other endocrine tumours. Pre- and postoperative laboratory findings were reviewed in a total of 115 patients with UA. Patients receiving perioperative dexamethasone (DEX) for nausea and vomiting prophylaxis were included as well.

Results

UA (51 right and 64 left) were performed in 47 women and 68 men (mean age 53.5 y.), laparoscopically in 97 (84.3%, 3 converted). UA indications included: Cushing (8), autonomous cortisol secretion (10, in 2 with combined Conn), Conn syndrome (37), pheochromocytoma (24), non-functioning adenoma (10, adrenal carcinoma (3), adrenal metastasis (19) and other diagnosis (4). 18 patients had a preoperative DST (15.7%). Anaesthesia reports revealed that 53/115 patients received DEX. 51/115 patients had a control of postoperative cortisol level. Hypocortisolemia was observed overall in 28/51 patients, by excluding Cushing patients in 24/45, in 19/53 patients who received DEX and in 7/48 in those without DEX. Confusion comes when patients receiving DEX had normal postoperative cortisolemia.

Conclusion

The fact that some patients received DEX (ERAS pathway), complicated the interpretation of cortisol levels at postoperative day one (D1). DEX is known to supress the hypothalamic-pituitary-adrenal axis (HPA axis) at D1. Thus, claiming that hypocortisolemia is the result of cortisol co-secretion (adenoma with double secretion), also able to supress the HPA axis, is not possible in patients who received DEX. These results suggests 1) to fully investigate all hormone functions in case of adrenal mass and 2) not administrating DEX in patients undergoing UA, for adequately assessing the HPA axis function postoperatively.
Immuno-activated highly expressed PD-1 phenotype in hepatocellular carcinoma is associated with lower recurrence
Authors: Hess G F , Ercan C , Coto-Llerena M , Zeindler J , Däster S , Muenst S , Bolli M , Vosbeck J , Kollmar O , Piscuoglio S , Soysal S D
Published: June 2022

Objective

Hepatocellular carcinoma (HCC) accounts for 75–85% of all primary liver malignancies. Curative treatments in early-stage HCC are hampered by high recurrence rates, and targeted therapies against HCC are rare. Little is known about the impact of tumor microenvironment (TME) in HCC. One immunomodulatory strategy used by malignant tumors is the expression of programmed cell death receptor 1 ligand (PD-L1), whose receptor is expressed on activated T cells (PD-1). The use of immune checkpoint inhibitors (ICI) blocking this interaction has shown antitumor activity and unprecedented rates of durable clinical responses in various cancer types. In HCC, ICI are described as possible second-line therapies. It is known from other tumor entities that expression of PD-1 and PD-L1 in the TME has prognostic importance and can predict response to ICI. The aim of our study was to investigate the impact of PD-1 and PD-L1 expression on HCC recurrence and its relation to cancer-immune phenotypes.

Methods

Immunohistochemical staining was performed on archival tissue from 94 HCC, primary and recurrent, using the following antibodies: NAT105 (PD-1) and Ventana SP263 (PD-L1). Based on this protein expression, tumors were classified as immunologically active, excluded or deserted. PD-1 and PD-L1 immunoreactivity was evaluated as the proportion of positive cells compared to the total number of immune cells (0%, <1%, and >1%).

Results

Basic tumor characteristics were not related to recurrence of HCC. PD-1 expression >1% (78%; 38/49) was associated with a significantly lower recurrence rate compared to tumors with <1% PD-1 expression (p=0.048). Of note, HCC classified as immune active were also enriched for PD-1 expression >1% (77%; 49/64). Additionally, they also showed a significantly lower recurrence rate, especially in combination with PD-1 expression of >1% (p=0.066). Conversely, an association between HCC recurrence and PD-L1 expression on tumor cells was not found.

Conclusion

Consistent with previous reports, an association between PD-1 expression on immune cells and lower HCC recurrence was found. Furthermore, the results suggest that HCC recurrence is less frequent in immune-activated tumors. The use of therapeutic anti-PD-1 antibodies as an adjuvant therapy should thus be further investigated.