bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival outcomes and surgical morbidity based on surgical approach to pulmonary metastasectomy in pediatric, adolescent and young adult patients with osteosarcoma
Authors: Kuo Christopher , Malvar Jemily , Chi Yueh‐Yun , Kim Eugene S. , Shah Rachana , Navid Fariba , Stein James E. , Mascarenhas Leo
Published: October 2023

Background

Thoracotomy is considered the standard surgical approach for the management of pulmonary metastases in osteosarcoma (OST). Several studies have identified the advantages of a thoracoscopic approach, however, the clinical significance of thoracotomy compared to thoracoscopy is yet to be evaluated in a randomized trial.

Aims

The primary aim was to determine the survival outcomes in OST patients based on surgical approach for pulmonary metastasectomy (PM) and secondary aim was to assess the post‐operative morbidities of OST PM through various surgical approaches.

Materials and Methods

We conducted a single institution retrospective study to compare survival outcomes and surgical morbidity according to the surgical approach of the management of pulmonary metastases in patients with OST.

Results

Sixty‐one patients with OST underwent PM. Twenty‐one patients were metastatic at diagnosis and underwent PM during primary treatment; nine had thoracotomy, six thoracoscopy, and six combined thoracoscopy with thoracotomy (CTT). Forty‐three patients with first pulmonary relapse or progression underwent PM; 18 had thoracotomy, 16 thoracoscopy and nine CTT. There was no difference in survival between surgical approaches. There were significantly more postoperative morbidities associated with thoracotomy for initial PM (pain and postoperative chest tube placement), and for PM at first relapse (pneumothoraces, pain, Foley catheter use and prolonged hospitalizations).

Conclusion

Our study demonstrates that patients with OST pulmonary metastases have comparable poor outcomes despite varying surgical approaches for PM. There were significantly more postoperative morbidities associated with thoracotomy for PM. Surgical bias and other competing risks could not be assessed given the limitations of a retrospective study and may be addressed in a prospective trial evaluating surgical approach for PM in OST.
Analysing Megasynthetase Mutants at High Throughput Using Droplet Microfluidics**
Authors: Pourmasoumi Farzaneh , Hengoju Sundar , Beck Katharina , Stephan Philipp , Klopfleisch Lukas , Hoernke Maria , Rosenbaum Miriam A. , Kries Hajo
Published: October 2023

Nonribosomal peptide synthetases (NRPSs) are giant enzymatic assembly lines that deliver many pharmaceutically valuable natural products, including antibiotics. As the search for new antibiotics motivates attempts to redesign nonribosomal metabolic pathways, more robust and rapid sorting and screening platforms are needed. Here, we establish a microfluidic platform that reliably detects production of the model nonribosomal peptide gramicidin S. The detection is based on calcein‐filled sensor liposomes yielding increased fluorescence upon permeabilization. From a library of NRPS mutants, the sorting platform enriches the gramicidin S producer 14.5‐fold, decreases internal stop codons 250‐fold, and generates enrichment factors correlating with enzyme activity. Screening for NRPS activity with a reliable non‐binary sensor will enable more sophisticated structure‐activity studies and new engineering applications in the future.
Epstein–Barr virus infection leading to multiorgan involvement in an immunocompetent man
Authors: Paymannejad Saina , Shirani Kiana , Najafi Mohammad Amin , Khorvash Farzin , Shamlou Farid
Published: October 2023

Key Clinical Message

Epstein–Barr virus (EBV) is a commonly asymptomatic widespread human herpes virus affecting over 90% of the population. It mostly originates complications like simple sore throat and infectious mononucleosis but severe manifestations are rare. Herein we report a 30‐year‐old immunocompetent man who presented with fever, sore throat, general weakness, and drowsiness. The diagnosis was formulated based on the positive RT‐PCR test for EBV DNA and serological detection of IgM antibody against viral capsid antigen. The patient developed severe meningoencephalitis, myocarditis, and bowel perforation and passed away after 72 days of hospitalization.
Development of Fine Particle Mechanical Separation Processes with Representative Catalyst Materials for Recycling PEM Water Electrolyzers Exploiting their Wetting Characteristics
Authors: Ahn Sohyun , Rudolph Martin
Published: October 2023

Demand for technologies using water electrolysis to produce green hydrogen is increasing, although recycling research on membrane electrode assemblies, which contain various precious and highly critical metals, is still limited. This study therefore aims at exploiting the feasibility of fine particle separation processes based on the difference in hydrophobicity of the ultrafine materials used as catalysts in polymer electrolyte membrane electrolyzers and at providing a fundamental study with representative materials of carbon black and TiO2. Since the cathode materials including carbon black are hydrophobic and the anode materials as well as TiO2 are hydrophilic, the characterizations of their various surface properties such as zeta potentials, dispersion characteristics, and bubble coverage angle tests have been investigated. In addition, using liquid‐liquid particle extraction in a mixture model, 99 % of carbon black is recovered in the organic phase and 97 % of TiO2 is selectively separated in the aqueous phase with the help of the dispersant, sodium hexametaphosphate.
Catalyst‐Free Propargylboration of Ketones with Allenyl‐Bpins: Highly Stereoselective Synthesis of tert‐Homopropargyl Alcohols Bearing Vicinal Stereocenters
Authors: Zhang Qian‐Cheng , Zhong Qin , Zhao Jian
Published: October 2023

A practical and efficient propargylboration of ketones is presented using general allenylboronic acid pinacol esters (allenyl‐Bpins) without a catalyst. This reaction is triggered by in‐situ activation of stable allenyl‐Bpins through the sequential addition of 1.25 equiv. of nBuLi and the prerequisite 2.0 equiv. of TFAA. Under the optimized reaction conditions, the versatile trisubstituted allenyl‐Bpins react with various ketones smoothly to afford a wide range of tert‐homopropargyl alcohols bearing vicinal stereocenters in high yields with good to excellent diastereoselectivities. Furthermore, propargylboration of ketones with chiral trisubstituted allenyl‐Bpins allows for the asymmetric synthesis of chiral tert‐homopropargyl alcohols with a full chirality transfer.
Automatisierte Demontage elektrischer Antriebsaggregate: Herausforderungen und Lösungsansätze
Authors: Hansen Florian , Hochstädt Daniel , Sauter Andreas , Seelig Jan H.
Published: October 2023

Die automatisierte Demontage von Antriebsaggregaten aus Elektrofahrzeugen ist eine Möglichkeit, die Elektromobilität der Zukunft nachhaltiger zu gestalten. Zunächst werden die Hintergründe und der Stand der Technik beleuchtet sowie die Vorteile einer automatisierten Demontage aufgezeigt. Hieraus ergeben sich konkrete Herausforderungen, von denen einige aufgegriffen und Lösungsansätze präsentiert werden. Diese umfassen die Konzeption des Demontagemoduls, das Handling des Modellprodukts und Lösungen zur automatisierten zerstörungsfreien Demontage des Rotors sowie von Schraubverbindungen.
70 Jahre Verfahrenstechnik an der TU Dresden
Authors: Beckmann Michael , Babick Frank , Eckert Kerstin , Heitkam Sascha , Schubert Markus , Urbas Leon , Stintz Michael
Published: October 2023

An der Technischen Hochschule Dresden, der Vorgängereinrichtung der TU Dresden, wurde 1953 mit der Besetzung der Fachprofessur für Verfahrenstechnik eine Fachrichtung „Ingenieur für Verfahrenstechnik“ eingerichtet und das heutige Institut für Verfahrenstechnik und Umwelttechnik begründet. Seitdem wurde das Profil in Ausbildung und Forschung des Instituts innerhalb der Fakultät Maschinenwesen der Technische Universität Dresden (TUD) erheblich weiterentwickelt. Ausgehend von dieser Entwicklung werden die heutigen Forschungsschwerpunkte der fünf Professuren und Arbeitsgruppen vorgestellt.
Folic Acid‐Modified Nanoprobe for In Vivo‐Targeted Persistent Luminescence Imaging and pH‐Responsive Antibiotic Therapy of Bacterial Infection
Authors: Wang Li‐Ya , Yan Li‐Xia , Zhao Xu , Chen Li‐Jian , Yan Xiu‐Ping
Published: October 2023

Low antibiotic utilization and inability to achieve real‐time monitoring of pathological status and treatment processes often result in unsatisfactory performance against bacterial infection. Developing a targeting antibacterial nanoprobe combining imaging with stimulus‐response antibiotic release is a promising strategy to precisely recognize lesions and enhance therapeutic efficacy for bacterial infection. In this work, we report a pH‐responsive theragnostic nanoplatform for targeted imaging and local drug release at the bacterial infection site. The nanoplatform consists of the core‐shell structure with persistent luminescence nanoparticles (PLNPs) as the core for autofluorescence‐free luminescence imaging and zeolitic imidazolate framework‐8 (ZIF‐8) as the shell to act as a carrier for antibiotics cefazolin. The core‐shell nanostructure is further conjugated with folic acid to facilitate the uptake and accumulation of the nanoparticles, and realize the autofluorescence‐free targeted imaging of the infection site. The acidic microenvironment at the bacterial infection site enables ZIF‐8 to decompose for specific drug release improve the performance in bacterial infection treatment. The developed pH‐responsive nanotheranostic probe is promising for autofluorescence‐free targeted imaging and therapy of bacterial infection.
Analysis of timing jitter in digital transmission systems
Authors: Miyauchi Kazuhiro , Wakabayashi Isamu , Shibayama Hiroki
Published: October 2023

An analysis of timing jitter generation in band‐limited digital systems is presented. An integral representation of jitter spectral density in frequency domain is derived for typical transmission systems: baseband polar system, BPSK and QPSK with AWGN. Using the representation, one can calculate the jitter spectral density and jitter variance for any frequency characteristics of the channel by performing integration over a finite frequency domain. The jitter spectral density consists of three terms with different noise dependency, each of which is represented by a combination of three factors: a coefficient, tank function, and jitter source spectral density. As a typical application of the present theory, the jitter spectral density and rms jitter are calculated for a cosine rolloff scheme. The jitter dependency on the rolloff factor, Eb/N0, and timing tank parameters are calculated and discussed. © 2001 Scripta Technica, Electron Comm Jpn Pt 1, 84(8): 1–13, 2001
Impact of adherence to guideline‐directed therapy on risk of death in HF patients across an ejection fraction spectrum
Authors: Chen Xiaojing , Kang Yu , Dahlström Ulf , Fu Michael
Published: October 2023

Aims

How different degrees of adherence to guideline‐directed medical therapy (GDMT) affect mortality risk in patients with heart failure (HF) in a real‐world clinical setting is poorly understood. This study sought to investigate how different levels of adherence to GDMT were associated with the risk of all‐cause mortality in patients with HF across a spectrum of left ventricular ejection fractions (LVEFs) in a real‐world clinical setting.

Methods and results

A total of 64 610 HF patients with no missing value of LVEF from the Swedish Heart Failure Registry were included in the study. Patients were divided according to different LVEFs (<30%, 30–39%, 40–49%, and≥50%) and stratified by an adherence score (good, moderate, or poor) according to the triple, double, and single one usage of GDMT: angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, beta‐blockers, and mineralocorticoid receptor antagonists. The outcome is time to all‐cause mortality. The mean age of the whole cohort was 73.9 ± 12.1 years, and the proportion of patients in LVEF < 30%, 30–39%, 40–49%, and≥50% groups was 27.6%, 26.9%, 22.1%, and 23.3%, respectively. Patients with LVEF < 30% had the highest mortality rate, almost 20% higher than those with LVEF ≥ 50% {hazard ratio [HR] [95% confidence interval (CI)]: 0.80 [0.71–0.90], P < 0.001}. After treatment of GDMT with good adherence, patients with LVEF < 30% had similar mortality to those with LVEF ≥ 50% [HR (95% CI): 0.97 (0.86–1.10), P = 0.664]. However, the percentage of moderate or poor GDMT was alarmingly high, with good adherence only in 20% of the patients.

Conclusions

Good adherence to GDMT works best in patients with LVEF < 50%, whereas moderate adherence to GDMT varies in efficacy depending on the components of the drug combinations.
Machine learning‐based classification of Alzheimer's disease and its at‐risk states using personality traits, anxiety, and depression
Authors: Waschkies Konrad F. , Soch Joram , Darna Margarita , Richter Anni , Altenstein Slawek , Beyle Aline , Brosseron Frederic , Buchholz Friederike , Butryn Michaela , Dobisch Laura , Ewers Michael , Fliessbach Klaus , Gabelin Tatjana , Glanz Wenzel , Goerss Doreen , Gref Daria , Janowitz Daniel , Kilimann Ingo , Lohse Andrea , Munk Matthias H. , Rauchmann Boris‐Stephan , Rostamzadeh Ayda , Roy Nina , Spruth Eike Jakob , Dechent Peter , Heneka Michael T. , Hetzer Stefan , Ramirez Alfredo , Scheffler Klaus , Buerger Katharina , Laske Christoph , Perneczky Robert , Peters Oliver , Priller Josef , Schneider Anja , Spottke Annika , Teipel Stefan , Düzel Emrah , Jessen Frank , Wiltfang Jens , Schott Björn H. , Kizilirmak Jasmin M.
Published: October 2023

Background

Alzheimer's disease (AD) is often preceded by stages of cognitive impairment, namely subjective cognitive decline (SCD) and mild cognitive impairment (MCI). While cerebrospinal fluid (CSF) biomarkers are established predictors of AD, other non‐invasive candidate predictors include personality traits, anxiety, and depression, among others. These predictors offer non‐invasive assessment and exhibit changes during AD development and preclinical stages.

Methods

In a cross‐sectional design, we comparatively evaluated the predictive value of personality traits (Big Five), geriatric anxiety and depression scores, resting‐state functional magnetic resonance imaging activity of the default mode network, apoliprotein E (ApoE) genotype, and CSF biomarkers (tTau, pTau181, Aβ42/40 ratio) in a multi‐class support vector machine classification. Participants included 189 healthy controls (HC), 338 individuals with SCD, 132 with amnestic MCI, and 74 with mild AD from the multicenter DZNE‐Longitudinal Cognitive Impairment and Dementia Study (DELCODE).

Results

Mean predictive accuracy across all participant groups was highest when utilizing a combination of personality, depression, and anxiety scores. HC were best predicted by a feature set comprised of depression and anxiety scores and participants with AD were best predicted by a feature set containing CSF biomarkers. Classification of participants with SCD or aMCI was near chance level for all assessed feature sets.

Conclusion

Our results demonstrate predictive value of personality trait and state scores for AD. Importantly, CSF biomarkers, personality, depression, anxiety, and ApoE genotype show complementary value for classification of AD and its at‐risk stages.
Perioperative complications among head and neck surgery patients with COVID‐19
Authors: Martin Ann M. , Elliott Zachary T. , Chisolm Paul , Crossley Jason , Maxwell Jessica H. , Pierce Matthew , Giurintano Jonathan
Published: October 2023

Background

Patients undergoing surgery for head and neck cancer (HNC) have potentially high perioperative complication rates. Recent studies indicate that preoperative COVID‐19 infection poses increased risk for postoperative complications in other fields. However, to date, there has not been data showing the effect of COVID‐19 on complication rates for HNC. Here, a large database was employed to assess if perioperative COVID‐19 increased the risk of perioperative complications among those undergoing HNC surgery.

Methods

A retrospective investigation was conducted using a multi‐institutional research database. Subjects who underwent HNC surgery from January 2020 to September 2022 were identified using the International Classification of Diseases and Current Procedure Terminology codes. Thirty‐day surgical and medical complications were assessed for those diagnosed with COVID‐19 infection from 7 days before or after surgery compared to those who were COVID‐19 negative. Cohorts were propensity scores matched by age, sex, and race.

Results

Perioperative COVID‐19 was present in n = 208 and absent in n = 15 158 subjects that underwent HNC surgery. For unmatched analyses, there was a statistically significant increased risk in the 30‐day postoperative period in COVID‐19‐positive patients for the following surgical complications: surgical site fistula, free tissue transfer (FTT) complication, FTT failure, and death. Additionally, there was a statistically significant increased risk in the 30‐day postoperative period in COVID‐19‐positive patients for the following medical complications: ventilator support, pneumonia, vasopressor, acute renal failure, and myocardial infarction.

Conclusion

This large, retrospective populational study suggests HNC patients are at increased risk for death and several perioperative complications. This investigation is the first to address this clinical question.
The evolutionary advantages of chelonians are making them vulnerable to extinction in the Anthropocene
Authors: Bu Rongping , Lee Tien M. , Shi Haitao
Published: October 2023

Chelonians have survived for more than 200 million years. The distinct form of the chelonian shell stands as a testament to their enduring success, having survived millions of years of natural selection pressures. Unfortunately, traits and strategies that once ensured their survival—including their shell, strong environmental tolerance, long lifespan, and temperature‐dependent sex determination—are turning into disadvantages, particularly in the Anthropocene. This article outlines how this evolutionary success story is now on the brink of an extinction crisis.
Cell‐Cell Interactions in the Testis of Adjuvant‐Induced Arthritic Rat
Authors: ASIRVATHAM ANGELA L. , BRUOT BRENT C.
Published: October 2023

Rats with adjuvant‐induced arthritis (AA) have low levels of serum testosterone, and production of testosterone reportedly is influenced by macrophage secretory products. This study was undertaken to understand the mechanism mediating this hypoandrogenism. Testicular macrophages from AA and nonarthritic (NA)rats were cultured, and conditioned media was added to testicular interstitial cells and Percoll‐purified cells from NA rats. Testosterone production by interstitial cells stimulated with luteinizing hormone (LH) and incubated with adjuvant‐induced arthritic macrophage conditioned medium (AAMCM) was significantly lower than in cells incubated with nonarthritic macrophage conditioned medium (NAMCM). However, there was no difference in testosterone production by Percoll‐purified Leydig cells and those stimulated with LH when incubated with AAMCM or NAMCM. To determine whether an intermediary cell type was involved in mediating inhibition of testosterone production, AAMCM and NAMCM were added to a reconstituted preparation of testicular interstitial cells. Addition of AAMCM restored the inhibitory effect, suggesting that arthritic hypoandrogenism is mediated by cell‐cell interaction. These results suggest that a factor produced by macrophages from AA rats appears to mediate testosterone production by acting in conjunction with other cells in the testicular interstitium.
Contraceptive Steroids Influence the Hemostatic Activation State in Healthy Men
Authors: ZITZMANN MICHAEL , JUNKER RALF , KAMISCHKE AXEL , NIESCHLAG EBERHARD
Published: October 2023

Hormonal contraception for men requires administration of testosterone and gestagens. The effects of a long‐acting testosterone ester and 2 different progestins on hemostatic activation parameters were studied in relation to cardiovascular risk. In phase 1, 7 healthy men aged 28–38 years received a single intramuscular injection of 200 mg norethisterone‐enanthate (NET‐EN) on Day 0. Plasma samples were obtained on Days 0, 14, 41, and 84. In phase 2, 3 groups of 14 healthy men aged 18–45 years received four injections (every 6 weeks) of 1000 mg testosterone undecanoate (TU), plus daily oral placebo or daily oral levonorgestrel (LNG, 250 μg); or four injections (every 6 weeks) of NET‐EN. Treatment lasted 24 weeks. Plasma samples were obtained at weeks 0, 16, 24, and 52. All samples were assayed for levels of coagulation factors VIIc, VIIa, XIIc, and XIIa; prothrombin fragment F1+2 (F1+2); antithrombin; plasmin‐α2‐anti‐plasmin‐complex (PAP); and fibrinogen. NET‐EN alone led to a depletion of sexual hormones and a marked shift in hemostatic parameters with increasing levels of FXIIc, fibrinogen, antithrombin, and F1+2, whereas FVIIc and FVIIa levels decreased. PAP levels increased significantly. Opposite effects were seen in the TU/placebo group, with a significant down‐regulation of fibrinolysis and the hemostatic turnover rate. Testosterone effects were attenuated by additional administration of gestagens. The effect of hormonal male contraception using long‐acting testosterone esters with or without gestagens was significantly measurable within the hemostatic system. Down‐regulation of the hemostatic system with testosterone alone may indicate an antithrombotic effect, whereas clinical consequences of an additional gestagen compound cannot be derived.
Bicarbonate Stimulation of Boar Sperm Motility via a Protein Kinase A—Dependent Pathway: Between‐Cell and Between‐Ejaculate Differences Are Not Due to Deficiencies in Protein Kinase A Activation
Authors: HOLT WILLIAM V. , HARRISON ROBIN A. P.
Published: October 2023

Because poorly motile sperm samples can often be stimulated by treatments that increase intracellular levels of cyclic adenosine monophosphate (cAMP), it has been supposed that such samples are unable to maintain an adequate supply of the cyclic nucleotide with which to activate protein kinase A (PKA). To investigate this hypothesis, we incubated boar sperm samples with bicarbonate (a stimulator of adenylyl cyclase) and compared its effect with that of 5,6‐dichloro‐1‐beta‐D‐ribofuranosyl‐benzimidazole 3‘,5’‐cyclic monophosphothioate (cBIMPS, a highly permeable and stable cAMP analog). Videomicroscopy assessment of motility was followed by computer analysis of the sperm tracks to produce motility descriptor values for many individual cells in each sample, whence “cluster” analysis of these data identified groups of spermatozoa that differed in motility characteristics. Bicarbonate stimulation of motility was characterized by an increase in the linearity (LIN) and progressive velocity of part of the sperm population only. The size of this “fast linear” subpopulation varied considerably between ejaculates. However, treatment with cBIMPS did not induce significantly more “fast linear” sperm than treatment with bicarbonate. In further experiments investigating the role of protein kinases in motility control, bicarbonate stimulation was greatly inhibited by H89 (a specific inhibitor of PKA), whereas GF109203X and lavendustin A (inhibitors of protein kinase C [PKC] and protein tyrosine kinase [PTK], respectively) had essentially no effect. While inclusion of the protein phosphatase inhibitor calyculin stimulated motility, it failed to increase the overall percentage of “fast linear sperm” induced by bicarbonate. We conclude that intersperm and interejaculate differences in boar sperm motility are not due to inadequacy in cAMP supply or to ineffective PKA activity.
Intrinsic factors behind long‐COVID: II. SARS‐CoV‐2, extracellular vesicles, and neurological disorders
Authors: El‐Maradny Yousra A. , Rubio‐Casillas Alberto , Mohamed Kareem I. , Uversky Vladimir N. , Redwan Elrashdy M.
Published: October 2023

With the decline in the number of new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) infections, the World Health Organization announced the end of the SARS‐CoV‐2 pandemic. However, the repercussions of this viral pandemic may remain with us for a longer period of time, as it has remodeled the lives of humankind in many ways, including social and economic. Of course, its most important repercussions remain on the human health level. Long‐coronavirus disease (COVID) or post‐COVID is a state for which we do not have a concrete definition, a specific international classification of diseases Code, clear diagnostic tools, or well‐known effective cures as of yet. In this second article from the Intrinsic Factors behind long‐COVID Series, we try to link long‐COVID symptoms with their causes, starting from the nervous system. Extracellular vesicles (ECVs) play very complex and ramified roles in the bodies of both healthy and not‐healthy individuals. ECVs may facilitate the entry of many bioactive molecules and pathogens into the tissues and cells of the nervous system across the blood–brain barrier. Based on the size, quantity, and quality of their cargo, ECVs are directly proportional to the pathological condition and its severity through intertwined mechanisms that evoke inflammatory immune responses typically accompanied by pathological symptoms over variable time periods according to the type of these symptoms.
High throughput selection of organic cathode materials
Authors: López‐Carballeira Diego , Polcar Tomáš
Published: October 2023

Efficient and affordable batteries require the design of novel organic electrode materials to overcome the drawbacks of the traditionally used inorganic materials, and the computational screening of potential candidates is a very efficient way to identify prospective solutions and minimize experimental testing. Here we present a DFT high‐throughput computational screening where 86 million molecules contained in the PUBCHEM database have been analyzed and classified according to their estimated electrochemical features. The 5445 top‐performing candidates were identified, and among them, 2306 are expected to have a one‐electron reduction potential higher than 4 V versus (Li/Li+). Analogously, one‐electron energy densities higher than 800 Whkg−1 have been predicted for 626 molecules. Explicit calculations performed for certain materials show that at least 69 candidates with a two‐electron energy density higher than 1300 Whkg−1. Successful molecules were sorted into several families, some of them already commonly used electrode materials, and others still experimentally untested. Most of them are small systems containing conjugated CO, NN, or NC functional groups. Our selected molecules form a valuable starting point for experimentalists exploring new materials for organic electrodes.
Evaluation and comparison of immune responses induced by two Mpox mRNA vaccine candidates in mice
Authors: Yang Xidan , Hu Congxia , Yang Xuetao , Yang Xiu , Hu Xing , Wang Xingyun , Liu Cong , Yuan Yuan , Du Shouwen , Wang Peng George , Lin Jihui
Published: October 2023

The epidemic of Mpox virus (MPXV) from May 2022 was once declared as a Public Health Emergency of International Concern by the World Health Organization. Vaccines play an important role in prevention of infectious diseases, and mRNA vaccine technology was proved to be a safe and effective platform with successful application in defense of coronavirus disease 2019. In this study, based on A29L, M1R, A35R, and B6R of MPXV, we developed two MPXV mRNA vaccine candidates, designated as MPXfus and MPXmix. The MPXfus was one‐component, in which these four antigen proteins were linked in tandem by flexible linker and encoded by an individual mRNA as a fusion protein. The MPXmix was multicomponent containing four mRNA, and each mRNA encoded one antigen protein respectively. Mice were immunized with equal quality of MPXfus or MPXmix, delivered by lipid nanoparticles for evaluation and comparison of the immune responses induced by these two MPXV vaccine candidates. Results of immune response analyses indicated that both MPXfus and MPXmix could elicit high‐level of antigen‐specific antibodies and robust cellular immune response in mice. Moreover, results of virus neutralization assays suggested that sera from MPXfus‐ or MPXmix‐immunized mice possessed high neutralizing activities against vaccinia virus. In addition, titers of antigen‐specific antibody, levels of cellular immune response, and activities of neutralizing antibody against vaccinia virus induced by MPXfus and MPXmix presented no significant difference. In summary, this study provides valuable insights for further clinical development of one‐component and multicomponent mRNA vaccine candidates for the prevention of MPXV and other orthomyxoviruses.
Percutaneous transphyseal screw induces varus proximal femoral growth modulation in a growing pig model—A three‐dimensional analysis
Authors: Kutschke Michael J. , Kim Harry K. W.
Published: October 2023

Bone and joint angular deformities are common pediatric orthopedic problems that are often corrected surgically. Previous studies successfully demonstrated proximal femoral growth modulation in animal models, however outcome measurements were limited by two‐dimensional analysis. In this study, six Yorkshire cross male piglets were treated with unilateral percutaneous transphyseal screw placement across the medial aspect of the proximal femoral physis and analyzed using three‐dimensional (3D) techniques. Three primary outcome measures were considered—physis angle, version, and femoral length. Compared to paired controls, all treated femurs displayed varus correction and shortening after an average treatment period of 10 weeks. The amount of varus change was 11.6 ± 2.8° (mean ± SD) (p = 0.0002, 95% confidence interval [CI] [8.659, 14.589]) and shortening was 4.3 ± 1.6 mm (p = 0.0011, 95% CI [2.672, 5.942]). Four animals demonstrated retroversion and two demonstrated anteversion compared to controls (4.1 ± 5.4° retroversion, p = 0.1169, 95% CI [−1.483, 9.765]). The amount of varus correction was strongly correlated with the orientation of the screw relative to the medial/lateral axis of the physis (r = −0.887, p = 0.0183, 95% CI [−0.988, −0.271]). The amount and direction of version was strongly correlated with how eccentrically anterior or posterior the screw was placed relative to the center of the physis (r = −0.850, p = 0.0322, 95% CI [−0.983, −0.123]) as well as the angle of the screw relative to the posterior condylar axis of the femur (r = −0.980, p = 0.0006, 95% CI [−0.998, −0.822]). This study is the first to use 3D analysis to quantify proximal femur growth modulation and identify associations between the growth modulation outcomes and screw placement parameters.
Gait and strength assessment following surgical repair by intramedullary nailing of isolated tibial shaft fracture
Authors: Canseco Karl , Becker Brittany M. , Muscott Rachel K. , Schmeling Gregory J. , Fritz Jessica M.
Published: October 2023

The objective of the study was to evaluate the long‐term strength and gait outcomes after intramedullary nailing of isolated tibial diaphyseal fractures. This retrospective cohort study was conducted at an academic Level I trauma center. Fifteen participants with isolated tibial diaphyseal fractures (OTA/AO 42) at least 2 years postoperative from intramedullary nailing (IMN) provided informed consent. The average age was 40 ± 14 (range, 24–69); there were nine men and six women. Knee flexion‐extension strength data were collected. Temporal‐spatial, kinematic, and kinetic gait parameters were measured and compared to historic control data. Participants completed the SF‐36 and shortened musculoskeletal function assessment questionnaires. The mean length of follow‐up between surgery and gait analysis was 6 ± 2 years. The fractured limb demonstrated deficits in quadriceps strength between 9.8% and 23.4% compared to the unaffected limb. Temporal‐spatial parameters revealed slower walking speed, shorter stride length, decreased cadence, and shorter single‐limb support time in the fractured limb. Altered kinematic and kinetic findings included a knee extension shift during stance, with an increased knee flexor moment demand and decreased total knee power during loading and midstance. These findings represent deficits in concentric and eccentric knee extensor activity. Additionally, the fractured limb demonstrated decreased ankle dorsiflexion during stance and diminished ankle push‐off power. Long‐term outcomes after IMN of tibial diaphyseal fractures demonstrate decreased quadriceps strength and altered gait parameters that may have implications to the high incidence of knee and ankle pain in the fractured limb.
The role of mitochondrial reactive oxygen species in chondrocyte mechanotransduction
Authors: Momin Aisha , Perrotti Simona , Waldman Stephen D.
Published: October 2023

Chondrocytes are mechanosensitive cells able to sense and respond to external mechanical stimuli through the process of mechanotransduction. Previous studies have demonstrated that mechanical stimulation causes mitochondrial deformation leading to mitochondrial reactive oxygen species (ROS) release in a dose‐dependent manner. For this reason, we focused on elucidating the role of mitochondrial ROS as anabolic signaling molecules in chondrocyte mechanotransduction. Chondrocyte‐seeded agarose gels were subjected to mechanical stimuli and the effect on matrix synthesis, ROS production, and mitogen‐activated protein kinases (MAPK) signaling was evaluated. Through the use of ROS‐specific staining, superoxide anion was the primary ROS released in response to mechanical stimuli. The anabolic effect of mechanical stimulation was abolished in the presence of electron transport chain inhibitors (complexes I, III, and V) and superoxide anion scavengers. Subsequent studies were centered on the involvement of MAPK pathways (ERK1/2, p38, and JNK) in the mechanotransduction cascade. While disruption of the ERK1/2 pathway had no apparent effect, the anabolic effect of mechanical stimulation was abolished in the presence of p38 and JNK pathway inhibitors. This suggest the involvement of apoptosis stimulating kinase 1 (ASK1), an upstream redox‐sensitive MAP3K shared by both the JNK and p38 pathways. Future experiments will focus on the involvement of the thioredoxin‐ASK1 complex which disassociates in the presence of oxidative stress, allowing ASK1 to phosphorylate several MAP2Ks. Overall, these findings indicate superoxide anion as the primary ROS released in response to mechanical stimuli and that the resulting anabolic effect on chondrogenic matrix biosynthesis arises from the ROS‐dependent activation of the p38 and JNK MAPKs.
Nonionic and anionic surfactants as flowback aids in hydraulic fracturing methods of crude oil production
Authors: Clements John
Published: October 2023

Surfactants find utility in hydraulic fracturing operations for their ability to modify rock wettability and increase the flowback of fracturing fluid following proppant delivery. The performance of a series of nonionic and anionic surfactants was evaluated by gravity drainage displacement testing. Alkylbenzenesulfonates having alkyl chains possessing at least 16 carbons were among the best performers, yet a similar surfactant having an alkyl chain possessing only ~12 carbons performed quite poorly. These data illustrate that a critical chain length exists for this series. Lauryldimethylamine oxide also performed well. In general, those surfactants possessing the greatest ionic character outperformed nonionic surfactants. Critical micelle concentration, surface tension, contact angle, relative solubility number, and hydrophilic–lipophilic balance were determined for each surfactant studied. Unexpectedly however, few correlations between any of these physical and surface properties and performance in gravity drainage displacement tests were identified, underscoring the complexity of selecting surfactants suitable in the application. These data suggest that more real‐world test methods, employing stationary phases, temperatures and pressures that better mimic the fields and individual wells being considered, are needed to better guide surfactant selection.
Foaming properties of milk samples collected at various processing stages in a dairy processing factory across two seasons
Authors: Ho Thao M , Bhandari Bhesh R , Bansal Nidhi
Published: October 2023

BACKGROUND

A foam layer makes an essential contribution to the quality of cappuccino‐style drinks. Poor foaming of milk occurs quite often, however, especially in summer. The reasons for this are still unknown. Although a substantial number of studies on the foaming process of milk have been reported, these studies have been laboratory based and have used laboratory or pilot‐scale equipment to simulate the processing conditions of a dairy processing factory. This study collected about 40 different samples across different processing stages in a dairy factory over two seasons (two batches per season) and investigated their composition and physical and foaming properties by mechanical mixing and steam injection.

RESULTS

The results showed that milk samples collected in summer had a significantly higher content of fat, free fatty acids, and Ca2+ ions, and larger particle sizes but a markedly lower concentration of protein and solid non‐fat, and surface tension than the samples collected in spring. These differences provided spring milk with a higher steam injection foamability than summer milk. However, steam injection foam stability, and mechanical mixing foamability and foam stability were not affected by seasonal factors. Milk samples collected in different batches within a season were almost identical with regard to the properties that were investigated.

CONCLUSION

The variations in composition and physical properties of milk collected between two seasons could be the reasons for their difference in foamability but not for foam stability. Processes such as standardization, homogenization, and pasteurization improved markedly the foaming properties of milk. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Carriers based on dairy by‐products and dehumidified‐air spray drying as a novel multiple approach towards improved retention of phenolics in powders: sour cherry juice concentrate case study
Authors: Barańska Alicja , Michalska‐Ciechanowska Anna , Wojdyło Aneta , Mykhailyk Viacheslav A. , Korinchevska Tetiana V. , Samborska Katarzyna
Published: October 2023

BACKGROUND

Sour cherry juice concentrate powder can serve as a modern, easy‐to‐handle, phenolics‐rich merchandise; however, its transformation into powdered form requires the addition of carriers. In line with the latest trends in food technology, this study valorizes the use of dairy by‐products (whey protein concentrate, whey, buttermilk, and mixes with maltodextrin) as carriers. A new multiple approach for higher drying yield, phenolics retention (phenolic acids, flavonols and anthocyanins) and antioxidant capacity of powders were tested as an effect of simultaneous decrease of drying temperature due to the drying air dehumidification and lower carrier content.

RESULTS

Dairy‐based carriers were effective for spray drying of sour cherry‐juice concentrate. The drying yield was increased and retention of phenolics was higher when compared with maltodextrin. The application of dehumidified air, which enabled the drying temperature to be reduced, affected drying yield positively, and also affected particle morphology and retention of phenolics (the phenolic content was approximately 30% higher than with spray drying).

CONCLUSIONS

The study proved that it is possible to apply dairy‐based by‐products to produce sour cherry juice concentrate powders profitably, lowering the spray‐drying temperature and changing the carrier content. Dehumidified air spray drying can be recommended for the production of fruit juice concentrate powders with improved physicochemical properties. © 2023 Society of Chemical Industry.
“Progressive myoclonic ataxia and developmental/epileptic encephalopathy associated with a novel homozygous mutation in TCN2 gene”
Authors: Oshi Mohammed Ahmed Mohammed , Alfaifi Jaber , Alqahtani Youssef Ali M. , Aljabri Mohammed Fahad , Kamal Naglaa M. , Althopaity Jwaher , Althobaiti Khalid A. , Almalki Abdullah M. , Abosabie Salma A. S. , Abosabie Sara A. , Sherbiny Hanan Sakr , Almanjoomi Saif K. , Abdallah Enas A. A.
Published: October 2023

Background

Transcobalamin II (TCN2) defect is a rare metabolic disorder associated with a range of neurological manifestations, including mild developmental delay, severe intellectual disability, ataxia, and, in some cases, seizures. Cobalamin, an essential nutrient, plays a crucial role in central nervous system myelination.

Clinical Presentation

We present a family with an index patient who exhibited progressive neurodevelopmental regression starting at 9 months of age, accompanied by myoclonic seizures, ataxia, and tremor. No significant hematological abnormalities were observed. Exome sequencing analysis identified a novel homozygous mutation, c.3G>A – P(Met1I), affecting the acceptor site of intron 4 of the TCN2 gene (chromosome 22: 31003321, NM_000355.4), leading to likely pathogenic variant potentially affecting translation. Following treatment with hydroxocobalamin, the patient demonstrated partial clinical improvement. He has a sibling with overt hematological abnormalities and subtle neurological abnormalities who is homozygous to the same mutation. Both parents are heterozygous for the same mutation.

Conclusions

In infants presenting with unexplained non‐specific neurological symptoms, irrespective of classical signs of vitamin B12 deficiency, evaluation for TCN2 defect should be considered. Early diagnosis and appropriate management can lead to favorable outcomes.
Federal maternal task force to increase care, reduce stigma
Authors: Canady Valerie A.
Published: October 2023

Observing the need to address this country's maternal mental health crisis, the U.S. Department of Health and Human Services (HHS) last month announced the formation of a new federal task force and other key actions that include the launch of a national public education campaign to combat stigma.
HIt Discovery using docking ENriched by GEnerative Modeling (HIDDEN GEM): A novel computational workflow for accelerated virtual screening of ultra‐large chemical libraries
Authors: Popov Konstantin I. , Wellnitz James , Maxfield Travis , Tropsha Alexander
Published: October 2023

Recent rapid expansion of make‐on‐demand, purchasable, chemical libraries comprising dozens of billions or even trillions of molecules has challenged the efficient application of traditional structure‐based virtual screening methods that rely on molecular docking. We present a novel computational methodology termed HIDDEN GEM (HItDiscovery usingDockingENriched byGEnerativeModeling) that greatly accelerates virtual screening. This workflow uniquely integrates machine learning, generative chemistry, massive chemical similarity searching and molecular docking of small, selected libraries in the beginning and the end of the workflow. For each target, HIDDEN GEM nominates a small number of top‐scoring virtual hits prioritized from ultra‐large chemical libraries. We have benchmarked HIDDEN GEM by conducting virtual screening campaigns for 16 diverse protein targets using Enamine REAL Space library comprising 37 billion molecules. We show that HIDDEN GEM yields the highest enrichment factors as compared to state of the art accelerated virtual screening methods, while requiring the least computational resources. HIDDEN GEM can be executed with any docking software and employed by users with limited computational resources.
Research on a capacitive MEMS pressure sensor based on through glass via
Authors: Fu Yingchun , He Fan , Jia Lu , Han Guowei , Si Chaowei , Zhang Meng
Published: October 2023

The paper reports the fabrication and characterization of a capacitive Microelectro Mechanical Systems pressure sensor based on through glass vias (TGV), which had a large dynamic range by operating in touch mode. The substrate with TGV offers the advantage of elimination of parasitic capacitances owing to the superior insulation property of glass. The fabrication process was introduced. In particular, anodic bonding was applied in high vacuum to realize the hermetic package to obtain large operating range and high sensitivity. The performance of the sensor with a sensitive diaphragm of 700 μm × 1400 μm was characterized in the pressure range from −80 to 180 kPa. The sensitivity was determined as 0.072 pF/kPa over the range of 160 kPa with a good linearity of 97%.
Wideband circularly polarized SIW cavity‐backed patches antenna for wide‐angle scanning phased arrays
Authors: Liu Hao , Fan Yulu , Xing Yu , Guan Tianci , Xu Xin , Xu Ziqiang , Qing Anyong , Lin Xianqi
Published: October 2023

A single‐feed wideband circularly polarized (CP) substrate‐integrated waveguide (SIW) cavity‐backed antenna and its phased array are presented in this paper. The proposed element consists of SIW cavity, stacked patches, and a 50‐Ω coaxial probe. The coaxial pin is directly connected to the two patch radiators. By chamfering on each rectangular patch, the proposed SIW cavity‐backed patch antenna realizes wideband circular polarization characteristic. The proposed element exhibits a simulated impedance bandwidth of 22.5% (14–17.6 GHz) for |S11| < −10 dB, an axial‐ratio (AR) bandwidth of 12.9% (14.5–16.5 GHz) for AR ≤ 3 dB. Simulation results illustrate that the infinite array can scanning up to ±60° in all planes over the operating frequency, under the criterion of active VSWR ≤ 3 and AR ≤ 3 dB. For verification purpose, an 8 × 8 array prototype was manufactured and measured. To achieve better CP characteristics, the sequential rotation technique is applied to the full array configuration. The measured results show good agreement with simulation results.