bluuebunny/crossref_metadata_2025 huggingface dataset:
S1P Released by SGPL1-Deficient Astrocytes Enhances Astrocytic ATP Production via S1PR2,4, Thus Keeping Autophagy in Check: Potential Consequences for Brain Health
Authors: Alam Shah , Afsar Sumaiya Yasmeen , Van Echten-Deckert Gerhild
Published: February 2023

Astrocytes are critical players in brain health and disease. Sphingosine-1-phosphate (S1P), a bioactive signaling lipid, is involved in several vital processes, including cellular proliferation, survival, and migration. It was shown to be crucial for brain development. Its absence is embryonically lethal, affecting, inter alia, the anterior neural tube closure. However, an excess of S1P due to mutations in S1P-lyase (SGPL1), the enzyme responsible for its constitutive removal, is also harmful. Of note, the gene SGPL1 maps to a region prone to mutations in several human cancers and also in S1P-lyase insufficiency syndrome (SPLIS) characterized by several symptoms, including peripheral and central neurological defects. Here, we investigated the impact of S1P on astrocytes in a mouse model with the neural−targeted ablation of SGPL1. We found that SGPL1 deficiency, and hence the accumulation of its substrate, S1P, causes the elevated expression of glycolytic enzymes and preferentially directs pyruvate into the tricarboxylic acid (TCA) cycle through its receptors (S1PR2,4). In addition, the activity of TCA regulatory enzymes was increased, and consequently, so was the cellular ATP content. The high energy load activates the mammalian target of rapamycin (mTOR), thus keeping astrocytic autophagy in check. Possible consequences for the viability of neurons are discussed.
Fibroblast Growth Factors for Nonalcoholic Fatty Liver Disease: Opportunities and Challenges
Authors: Tian Haoyu , Zhang Shuairan , Liu Ying , Wu Yifan , Zhang Dianbao
Published: February 2023

Nonalcoholic fatty liver disease (NAFLD), a chronic condition associated with metabolic dysfunction and obesity, has reached epidemic proportions worldwide. Although early NAFLD can be treated with lifestyle changes, the treatment of advanced liver pathology, such as nonalcoholic steatohepatitis (NASH), remains a challenge. There are currently no FDA-approved drugs for NAFLD. Fibroblast growth factors (FGFs) play essential roles in lipid and carbohydrate metabolism and have recently emerged as promising therapeutic agents for metabolic diseases. Among them, endocrine members (FGF19 and FGF21) and classical members (FGF1 and FGF4) are key regulators of energy metabolism. FGF-based therapies have shown therapeutic benefits in patients with NAFLD, and substantial progress has recently been made in clinical trials. These FGF analogs are effective in alleviating steatosis, liver inflammation, and fibrosis. In this review, we describe the biology of four metabolism-related FGFs (FGF19, FGF21, FGF1, and FGF4) and their basic action mechanisms, and then summarize recent advances in the biopharmaceutical development of FGF-based therapies for patients with NAFLD.
Insertion Depth Modulates Protein Kinase C-δ-C1b Domain Interactions with Membrane Cholesterol as Revealed by MD Simulations
Authors: Judge Patrick T. , Overall Sarah A. , Barnes Alexander B.
Published: February 2023

Protein kinase C delta (PKC-δ) is an important signaling molecule in human cells that has both proapoptotic as well as antiapoptotic functions. These conflicting activities can be modulated by two classes of ligands, phorbol esters and bryostatins. Phorbol esters are known tumor promoters, while bryostatins have anti-cancer properties. This is despite both ligands binding to the C1b domain of PKC-δ (δC1b) with a similar affinity. The molecular mechanism behind this discrepancy in cellular effects remains unknown. Here, we have used molecular dynamics simulations to investigate the structure and intermolecular interactions of these ligands bound to δC1b with heterogeneous membranes. We observed clear interactions between the δC1b-phorbol complex and membrane cholesterol, primarily through the backbone amide of L250 and through the K256 side-chain amine. In contrast, the δC1b-bryostatin complex did not exhibit interactions with cholesterol. Topological maps of the membrane insertion depth of the δC1b-ligand complexes suggest that insertion depth can modulate δC1b interactions with cholesterol. The lack of cholesterol interactions suggests that bryostatin-bound δC1b may not readily translocate to cholesterol-rich domains within the plasma membrane, which could significantly alter the substrate specificity of PKC-δ compared to δC1b-phorbol complexes.
Discovery and Optimization of Neutralizing SARS-CoV-2 Antibodies Using ALTHEA Gold Plus Libraries™
Authors: Guzmán-Bringas Omar U. , Gómez-Castellano Keyla M. , González-González Edith , Salinas-Trujano Juana , Vázquez-Leyva Said , Vallejo-Castillo Luis , Pérez-Tapia Sonia M. , Almagro Juan C.
Published: February 2023

We recently reported the isolation and characterization of anti-SARS-CoV-2 antibodies from a phage display library built with the VH repertoire of a convalescent COVID-19 patient, paired with four naïve synthetic VL libraries. One of the antibodies, called IgG-A7, neutralized the Wuhan, Delta (B.1.617.2) and Omicron (B.1.1.529) strains in authentic neutralization tests (PRNT). It also protected 100% transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from SARS-CoV-2 infection. In this study, the four synthetic VL libraries were combined with the semi-synthetic VH repertoire of ALTHEA Gold Libraries™ to generate a set of fully naïve, general-purpose, libraries called ALTHEA Gold Plus Libraries™. Three out of 24 specific clones for the RBD isolated from the libraries, with affinity in the low nanomolar range and sub-optimal in vitro neutralization in PRNT, were affinity optimized via a method called “Rapid Affinity Maturation” (RAM). The final molecules reached sub-nanomolar neutralization potency, slightly superior to IgG-A7, while the developability profile over the parental molecules was improved. These results demonstrate that general-purpose libraries are a valuable source of potent neutralizing antibodies. Importantly, since general-purpose libraries are “ready-to-use”, it could expedite isolation of antibodies for rapidly evolving viruses such as SARS-CoV-2.
Reproductive Suppression Caused by Spermatogenic Arrest: Transcriptomic Evidence from a Non-Social Animal
Authors: Yao Baohui , An Kang , Kang Yukun , Tan Yuchen , Zhang Degang , Su Junhu
Published: February 2023

Reproductive suppression is an adaptive strategy in animal reproduction. The mechanism of reproductive suppression has been studied in social animals, providing an essential basis for understanding the maintenance and development of population stability. However, little is known about it in solitary animals. The plateau zokor is a dominant, subterranean, solitary rodent in the Qinghai–Tibet Plateau. However, the mechanism of reproductive suppression in this animal is unknown. We perform morphological, hormonal, and transcriptomic assays on the testes of male plateau zokors in breeders, in non-breeders, and in the non-breeding season. We found that the testes of non-breeders are smaller in weight and have lower serum testosterone levels than those of breeders, and the mRNA expression levels of the anti-Müllerian hormone (AMH) and its transcription factors are significantly higher in non-breeder testes. Genes related to spermatogenesis are significantly downregulated in both meiotic and post-meiotic stages in non-breeders. Genes related to the meiotic cell cycle, spermatogenesis, flagellated sperm motility, fertilization, and sperm capacitation are significantly downregulated in non-breeders. Our data suggest that high levels of AMH may lead to low levels of testosterone, resulting in delayed testicular development, and physiological reproductive suppression in plateau zokor. This study enriches our understanding of reproductive suppression in solitary mammals and provides a basis for the optimization of managing this species.
A pH-Responsive Asymmetric Microfluidic/Chitosan Device for Drug Release in Infective Bone Defect Treatment
Authors: Chen Hongyu , Tan Wei , Tong Tianyi , Shi Xin , Ma Shiqing , Zhu Guorui
Published: February 2023

Bacterial infection is currently considered to be one of the major reasons that leads to the failure of guided bone regeneration (GBR) therapy. Under the normal condition, the pH is neutral, while the microenvironment will become acid at the sites of infection. Here, we present an asymmetric microfluidic/chitosan device that can achieve pH-responsive drug release to treat bacterial infection and promote osteoblast proliferation at the same time. On-demand release of minocycline relies on a pH-sensitive hydrogel actuator, which swells significantly when exposed to the acid pH of an infected region. The PDMAEMA hydrogel had pronounced pH-sensitive properties, and a large volume transition occurred at pH 5 and 6. Over 12 h, the device enabled minocycline solution flowrates of 0.51–1.63 µg/h and 0.44–1.13 µg/h at pH 5 and 6, respectively. The asymmetric microfluidic/chitosan device exhibited excellent capabilities for inhibiting Staphylococcus aureus and Streptococcus mutans growth within 24 h. It had no negative effect on proliferation and morphology of L929 fibroblasts and MC3T3-E1 osteoblasts, which indicates good cytocompatibility. Therefore, such a pH-responsive drug release asymmetric microfluidic/chitosan device could be a promising therapeutic approach in the treatment of infective bone defects.
Comparison of Point Cloud Registration Algorithms for Mixed-Reality Cross-Device Global Localization
Authors: Osipov Alexander , Ostanin Mikhail , Klimchik Alexandr
Published: February 2023

State-of-the-art approaches for localization and mapping are based on local features in images. Along with these features, modern augmented and mixed-reality devices enable building a mesh of the surrounding space. Using this mesh map, we can solve the problem of cross-device localization. This approach is independent of the type of feature descriptors and SLAM used onboard the AR/MR device. The mesh could be reduced to the point cloud that only takes vertices. We analyzed and compared different point cloud registration methods applicable to the problem. In addition, we proposed a new pipeline Feature Inliers Graph Registration Approach (FIGRA) for the co-localization of AR/MR devices using point clouds. The comparative analysis of Go-ICP, Bayesian-ICP, FGR, Teaser++, and FIGRA shows that feature-based methods are more robust and faster than ICP-based methods. Through an in-depth comparison of the feature-based methods with the usual fast point feature histogram and the new weighted height image descriptor, we found that FIGRA has a better performance due to its effective graph-theoretic base. The proposed pipeline allows one to match point clouds in complex real scenarios with low overlap and sparse point density.
Numerical Investigation of Pre-Stressed Reinforced Concrete Railway Sleeper for High-Speed Application
Authors: Major Zoltán , Ibrahim Sarah Khaleel , Rad Majid Movahedi , Németh Attila , Harrach Dániel , Herczeg Géza , Szalai Szabolcs , Kocsis Szürke Szabolcs , Harangozó Dóra , Sysyn Mykola , Kurhan Dmytro , Baranyai Gusztáv , Gáspár László , Fischer Szabolcs
Published: February 2023

The current paper deals with the numerical investigation of a unique designed pre-stressed reinforced concrete railway sleeper for the design speed of 300 km/h, as well as an axle load of 180 kN. The authors applied different methodologies in their research: traditional hand-made calculations and two types of finite element software. The latter were AxisVM and ABAQUS, respectively. During the calculations, the prestressing loss was not considered. The results from the three methods were compared with each other. The hand-made calculations and the finite element modeling executed by AxisVM software are adequate for determining the mechanical inner forces of the sleeper; however, ABAQUS is appropriate for consideration of enhanced and sophisticated material models, as well as the stress-state of the elements, i.e., concrete, pre-stressed tendons, etc. The authors certified the applicability of these methodologies for performing the dimensioning and design of reinforced concrete railway sleepers with pre-stressing technology. The research team would like to continue their research in an improved manner, taking into consideration real laboratory tests and validating the results from FE modeling, special material models that allow calculation of crackings and their effects in the concrete, and so that the real pattern of the crackings can be measured by GOM Digital Image Correlation (DIC) technology, etc.
High-Capacity Ion Batteries Based on Ti2C MXene and Borophene First Principles Calculations
Authors: Kolosov Dmitry A. , Glukhova Olga E.
Published: February 2023

In this paper, we report an ab initio study of a composite material based on Ti2C and borophene B12 as an anode material for magnesium-ion batteries. The adsorption energy of Mg, specific capacitance, electrical conductivity, diffusion barriers, and open-circuit voltage for composite materials are calculated as functions of Mg concentration. It is found that the use of Ti2C as a substrate for borophene B12 is energetically favorable; the binding energy of Ti2C with borophene is −1.87 eV/atom. The translation vectors of Ti2C and borophene B12 differ by no more than 4% for in the X direction, and no more than 0.5% in the Y direction. The adsorption energy of Mg significantly exceeds the cohesive energy for bulk Mg. The energy barrier for the diffusion of Mg on the surface of borophene B12 is ~262 meV. When the composite surface is completely covered with Mg ions, the specific capacity is 662.6 mAh g−1 at an average open-circuit voltage of 0.55 V (relative to Mg/Mg+). The effect of reducing the resistance of borophene B12 upon its binding to Ti2C is established. The resulting electrical conductivity of the composite Ti16C8B40 is 3.7 × 105 S/m, which is three times higher than the electrical conductivity of graphite. Thus, a composite material based on Ti2C and borophene B12 is a promising anode material for magnesium-ion batteries.
Predatory Capacity and Reproduction of Cyrtorhinus lividipennis (Hemiptera: Miridae) Adults Exposed to Low-Temperature Storage and Fitness of the F1 Generation
Authors: Zhong Yuqi , Liao Xiaolan , Hou Maolin
Published: February 2023

Low-temperature storage (LTS) is a way to adjust natural enemy development to meet field release needs and to protect natural enemies from the odds of long-distance transportation. The mirid bug Cyrtorhinus lividipennis Reuter (Hemiptera: Miridae) is an important predator of planthoppers and leafhoppers in rice fields. In this study, the LTS effects were measured on the predatory capacity and reproduction of the mirid adults (provided with 20% honey solution and stored at 13 °C for 12 days), and the fitness of the F1 generation of these adults. Higher predation of the eggs of the brown planthopper Nilaparvata lugens (Stål) (Hemiptera: Delphacidae) was observed in the post-storage females than in the control females. The functional responses of C. lividipennis adults, either exposed to LTS or not, to planthopper eggs fitted well with Holling type II functional responses. Longevity was not affected by LTS, whereas the number of offspring nymphs was 55.6% lower in the post-storage females than in the control females. The fitness of the offspring generation was not affected by the LTS of parental adults. The findings are discussed with their relevance to biological control.
New Color-Patterned Species of Microtendipes Kieffer, 1913 (Diptera: Chironomidae) and a Deep Intraspecific Divergence of Species by DNA Barcodes
Authors: Song Chao , Wang Le , Lei Teng , Qi Xin
Published: February 2023

The genus Microtendipes Kieffer (Diptera: Chironomidae) has a nearly worldwide distribution, comprising more than 60 species, which are further divided into two species groups based on larval stage. However, species delimitation and identification among the adults of this genus are controversial and uncertain. For instance, previous studies have provided many synonymies based on conspecific color pattern variations in Microtendipes species. Here, we used DNA barcode data to address Microtendipes species delimitation as well as to test whether color pattern variations can be diagnostic characters for interspecific identification. The 151 DNA barcodes used, 51 of which were contributed by our laboratory, represent 21 morphospecies. Species with specific color patterns could be accurately separated based on DNA barcodes. Consequently, the color patterns of adult males could be important diagnostic characters. The average intraspecific and interspecific sequence divergences were 2.8% and 12.5%, respectively, and several species exhibited deep intraspecific divergences higher than 5%. Molecular operational taxonomic units (OTUs) ranged from 21 to 73, based on methods including phylogenetic trees, the assemble species by automatic partitioning method, the Poisson tree process (PTP), and the general mixed Yule-coalescent (GMYC) method. As a result of these analyses, five new species were recognized (M. baishanzuensis sp. nov., M. bimaculatus sp. nov., M. nigrithorax sp. nov., M. robustus sp. nov., and M. wuyiensis sp. nov.).
Evidence of Transmission of Plasmodium vivax 210 and Plasmodium vivax 247 by Anopheles gambiae and An. coluzzii, Major Malaria Vectors in Benin/West Africa
Authors: Ossè Razaki A. , Tokponnon Filémon , Padonou Germain Gil , Glitho Mariette E. , Sidick Aboubakar , Fassinou Arsène , Koukpo Come Z. , Akinro Bruno , Sovi Arthur , Akogbéto Martin
Published: February 2023

Current diagnostic and surveillance systems in Benin are not designed to accurately identify or report non-Plasmodium falciparum (Pf) human malaria infections. This study aims to assess and compare the prevalence of circumsporozoite protein (CSP) antibodies of Pf and P. vivax (Pv) in Anopheles gambiae s.l. in Benin. For that, mosquito collections were performed through human landing catches (HLC) and pyrethrum spray catches (PSC). The collected mosquitoes were morphologically identified, and Pf, Pv 210, and Pv 247 CSP antibodies were sought in An. gambiae s.l. through the ELISA and polymerase chain reaction (PCR) techniques. Of the 32,773 collected mosquitoes, 20.9% were An. gambiae s.l., 3.9% An. funestus gr., and 0.6% An. nili gr. In An. gambiae s.l., the sporozoite rate was 2.6% (95% CI: 2.1–3.1) for Pf, against 0.30% (95% CI: 0.1–0.5) and 0.2% (95% CI: 0.1–0.4), respectively, for Pv 210 and Pv 247. P. falciparum sporozoite positive mosquitoes were mostly An. gambiae (64.35%), followed by An. coluzzii (34.78%) and An. arabiensis (0.86%). At the opposite, for the Pv 210 sporozoite-positive mosquitoes, An. coluzzii and An. gambiae accounted for 76.92% and 23.08%, respectively. Overall, the present study shows that P. falciparum is not the only Plasmodium species involved in malaria cases in Benin.
Abundance of Halyomorpha halys (Hemiptera: Pentatomidae) and Megacopta cribraria (Hemiptera: Plataspidae) in Soybean in Areas with Few Previous Sightings in Tennessee
Authors: Amarasekare Kaushalya G. , Link Richard H.
Published: February 2023

Halyomorpha halys (Stål) and Megacopta cribraria (Fabricius) are two exotic invasive pests that have invaded the United States in recent years. Halyomorpha halys can damage various fruits, vegetables, and field crops, such as soybean and corn, while Megacopta cribraria only attacks soybean and kudzu, a weed species. They are currently found in southeastern states and threaten soybean and other crops grown in the region. This study evaluated the seasonal abundance of H. halys and M. cribraria in soybeans in 2016 and 2017 in two counties in the central region of Tennessee, where both species had either a few sightings or none that were recorded when this research was being planned. Lures and sweep sampling were used to monitor H. halys, and sweep sampling was used to monitor M. cribraria. Halyomorpha halys was first detected in samples in late July. Their numbers increased in early to mid-September, reached the economic threshold in late Sept, and then started to decline. Megacopta cribraria was first detected in mid to late July, increased their populations in September, but did not reach the economic threshold and declined mid-October. Our results showed the seasonal abundances of H. halys and M. cribraria and their establishment in the central region of Tennessee.
Acute and Chronic Changes in Myocardial Work Parameters in Patients with Severe Primary Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair
Authors: Galli Elena , Hubert Pierre , Leurent Guillaume , Auffret Vincent , Panis Vasileios , L’Official Guillaume , Donal Erwan
Published: February 2023

Background: The noninvasive assessment of myocardial work (MW) allows for the evaluation of left ventricular (LV) performance by considering the effect of LV afterload. This study aims to evaluate the acute and chronic impact of transcatheter edge-to-edge repair (TEER) on MW parameters and LV remodeling in patients with severe primary mitral regurgitation (PMR). Methods: A total of 71 patients (age: 77 ± 9 years, females: 44%) with moderate–to-severe or severe PMR (effective regurgitant orifice: 0.57 ± 0.31 cm2; regurgitant volume: 80 ± 34 mL; LV end-systolic diameter: 42 ± 12 mm) underwent TEER after a global assessment by the heart team. MW indices were evaluated before the procedure, at hospital discharge, and at 1-year follow-up. LV remodeling was described as the percentage variation in LVEDV between baseline and 1-year follow-up. Results: TEER caused an acute reduction in LVEF, global longitudinal strain (GLS), global MW index (GWI), work efficiency (GWE), and mechanical dispersion (MD) and a significant increase in wasted work (GWW). One year after the procedure, GLS, GWI, GWE, and MD recovered, whereas GWW remained significantly impaired. Baseline GWW (β = −0.29, p = 0.03) was an independent predictor of LV reverse remodeling at 1-year follow-up. Conclusions: In patients with severe PMR undergoing TEER, the acute reduction in LV preload causes significant impairment to all the parameters of LV performance. Baseline GWW was the only independent predictor of LV reverse remodeling, suggesting that a lower myocardial energetic efficiency in the context of chronic preload increase might impact the left ventricular response to mitral regurgitation correction.
The Effect of Coronavirus Outbreak on the Utilization of Coronary Revascularization Procedures: An Interrupted Time Series Analysis
Authors: Sarria-Santamera Antonio , Petrov Alexandr , Yessimova Dinara , Ortega Miguel A , Zhumambayeva Saule , Asúnsolo Angel
Published: February 2023

The coronavirus disease 19 (COVID-19) pandemic represented a great challenge for health systems, which had to quickly readapt and dedicate most of their resources to managing this crisis. The postponement of programmed interventions such as coronary revascularization procedures represented a critical issue in the first wave of the COVID-19 pandemic, especially in the hardest-hit countries such as Spain. However, the precise consequences of the delay of coronary revascularizations are not clearly determined. In the present work, interrupted time series (ITS) analysis was used to evaluate the utilization rates and assessment of the risk profiles of patients receiving two main coronary revascularization procedures (percutaneous coronary intervention—PCI and coronary artery bypass graft—CABG) and compared them in the periods before and after March 2020 using the Spanish National Hospital Discharge Database (SNHDD). Our results show that the abrupt reorganization of hospital care that represented the first wave of COVID-19 in March 2020 in Spain led to a reduction in cases, which was accompanied by an increase in the risk profile of CABG patients, but not PCI. On the other hand, the risk profile of both coronary revascularization procedures began before the pandemic, showing a significant temporal trend toward an increase in the risk profile. Future works should be directed to study and validate our results, evaluating other databases, regions, or countries.
Clinical Factors Associated with Severity of Colonic Diverticular Bleeding and Impact of Bleeding Site
Authors: Amano Hirohito , Yamamoto Takatsugu , Ikusaka Ken , Aoki Naoaki , Sakurai Miyoko , Honda Taku , Maruyama Kyohei , Aoyagi Hitoshi , Isono Akari , Abe Koichiro , Asaoka Yoshinari , Kodashima Shinya , Tanaka Atsushi
Published: February 2023

Factors associated with serious colonic diverticular bleeding (CDB) are unclear, although the incidence of CDB has increased. We carried out this study to clarify factors associated with serious CDB and rebleeding. Subjects included 329 consecutive patients hospitalized for confirmed or suspected CDB between 2004 and 2021. Patients were surveyed regarding backgrounds, treatment, and clinical course. Of 152 with confirmed CDB, 112 showed bleeding from the right colon, and 40 did from the left colon. Patients received red blood cell transfusions in 157 (47.7%), interventional radiology in 13 (4.0%), and surgery in 6 (1.8%) cases. Early rebleeding within one month occurred in 75 (22.8%) patients, and late rebleeding within one year occurred in 62 (18.8%). Factors associated with red blood cell transfusion included confirmed CDB, anticoagulants, and high shock index. The only factor related to interventional radiology or surgery was confirmed CDB, which was also associated with early rebleeding. Late rebleeding was associated with hypertension, chronic kidney disease and past CDB. Right CDB showed higher rates of transfusion and invasive treatment than left CDB. Confirmed CDB had high frequencies of transfusion, invasive treatment, and early rebleeding. Right CDB seemed to be a risk for serious disease. Factors related to late rebleeding were different from those related to early rebleeding of CDB.
Vitamin D, a Regulator of Androgen Levels, Is Not Correlated to PSA Serum Levels in a Cohort of the Middle Italy Region Participating to a Prostate Cancer Screening Campaign
Authors: Crocetto Felice , Barone Biagio , D’Aguanno Giulio , Falcone Alfonso , de Vivo Rosamaria , Rienzo Monica , Recchia Laura , Di Zazzo Erika
Published: February 2023

Prostate cancer (PCa) is the most common non-cutaneous malignancy in men worldwide, and it represents the fifth leading cause of death. It has long been recognized that dietary habits can impact prostate health and improve the benefits of traditional medical care. The activity of novel agents on prostate health is routinely assessed by measuring changes in serum prostate-specific antigen (PSA) levels. Recent studies hypothesized that vitamin D supplementation reduces circulating androgen levels and PSA secretion, inhibits cell growth of the hormone-sensitive PCa cell lines, counteracts neoangiogenesis and improves apoptosis. However, the results are conflicting and inconsistent. Furthermore, the use of vitamin D in PCa treatments has not achieved consistently positive results to date. In order to assess the existence of a correlation between the PSA and 25(OH)vitamin D levels as widely hypothesized in the literature, we analyzed the serum PSA and 25(OH)vitamin D concentration on a cohort of one hundred patients joining a PCa screening campaign. Additionally, we performed medical and pharmacological anamnesis and analyzed lifestyle, as sport practice and eating habits, by administering a questionnaire on family history. Although several studies suggested a protective role of vitamin D in PCa onset prevention and progression, our preliminary results revealed a clear absence of correlation between the serum vitamin D and PSA concentration levels, suggesting that vitamin D has no impact on PCa risk. Further investigations enrolling a huge number of patients are needed with particular attention to vitamin D supplementation, calcium intake, solar radiation that influences vitamin D metabolism and other potential indicators of health to confirm the absence of correlation observed in our study.
Immunotherapy in Elderly Patients Affected by Non-Small Cell Lung Cancer: A Narrative Review
Authors: Montrone Michele , Rosati Gerardo , Longo Vito , Catino Annamaria , Massafra Raffaella , Nardone Annalisa , Pesola Francesco , Montagna Elisabetta Sara , Marech Ilaria , Pizzutilo Pamela , Galetta Domenico
Published: February 2023

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers, and most NSCLC is diagnosed in the advanced stage. The advent of immune check point inhibitors (ICIs) changed the therapeutic scenario both in metastatic disease (in first and subsequent lines) and earlier settings. Comorbidities, reduced organ function, cognitive deterioration, and social impairment give reasons for a greater probability of adverse events, making the treatment of elderly patients challenging. The reduced toxicity of ICIs compared to standard chemotherapy makes this approach attractive in this population. The effectiveness of ICIs varies according to age, and patients older than 75 years may benefit less than younger patients. This may be related to the so-called immunosenescence, a phenomenon that refers to the reduced activity of immunity with older age. Elders are often under-represented in clinical trials, even if they are a large part of the patients in a clinical practice. In this review, we aim to explore the biological aspects of immunosenescence and to report and analyze the most relevant and recent literature findings on the role of immunotherapy in elderly patients with NSCLC.
Diagnostic Role of mNGS in Polymicrobial Periprosthetic Joint Infection
Authors: Mei Jian , Hu Hongxin , Zhu Si , Ding Haiqi , Huang Zida , Li Wenbo , Yang Bin , Zhang Wenming , Fang Xinyu
Published: February 2023

Objectives: The purpose of this study was to explore the clinical value of metagenomic next-generation sequencing (mNGS) in the diagnosis of polymicrobial periprosthetic joint infection (PJI). Methods: Patients with complete data who underwent surgery at our hospital between July 2017 and January 2021 for suspected periprosthetic joint infection (PJI), according to the 2018 ICE diagnostic criteria, were enrolled, and all patients underwent microbial culture and mNGS detection, which were performed on the BGISEQ-500 platform. Microbial cultures were performed on two samples of synovial fluid, six samples of tissue, and two samples of prosthetic sonicate fluid for each patient. The mNGS was performed on 10 tissues, 64 synovial fluid samples, and 17 prosthetic sonicate fluid samples. The results of mNGS testing were based on the interpretation of mNGS results in the previous literature and the assertions of microbiologists and orthopedic surgeons. The diagnostic efficacy of mNGS in polymicrobial PJI was assessed by comparing the results of conventional microbial cultures and mNGS. Results: A total of 91 patients were finally enrolled in this study. The sensitivity, specificity, and accuracy of conventional culture for the diagnosis of PJI were 71.0%, 95.4%, and 76.9%, respectively. The sensitivity, specificity, and accuracy of mNGS for the diagnosis of PJI were 91.3%, 86.3%, and 90.1%, respectively. The sensitivity, specificity, and accuracy of conventional culture for the diagnosis of polymicrobial PJI were 57.1%, 100%, and 91.3%, respectively. mNGS had a sensitivity, specificity, and accuracy of 85.7%, 60.0%, and 65.2%, respectively, for the diagnosis of polymicrobial PJI. Conclusions: mNGS can improve the diagnosis efficiency of polymicrobial PJI, and the combination of culture and mNGS is a promising method to diagnose polymicrobial PJI.
Case Report: Spontaneous Left Inferior Epigastric Artery Injury in a COVID-19 Female Patient Undergoing Anticoagulation Therapy
Authors: Abrashev Hristo , Ananiev Julian , Georgieva Ekaterina
Published: February 2023

Since the beginning of the pandemic, a recommendation was made for the use of anticoagulants in high-risk hospitalized patients. This therapeutic approach has positive and negative effects regarding the outcome of the disease. Anticoagulant therapy prevents thromboembolic events, but it can also lead to spontaneous hematoma formation, or be accompanied by massive active bleeding. We present a 63-year-old COVID-19-positive female patient with a massive retroperitoneal hematoma and spontaneous left inferior epigastric artery injury.
Prevalence of Overweight and Obesity and Their Impact on Spirometry Parameters in Patients with Asthma: A Multicentre, Retrospective Study
Authors: Alqarni Abdullah A. , Aldhahir Abdulelah M. , Siraj Rayan A. , Alqahtani Jaber S. , Alshehri Hams H. , Alshamrani Amal M. , Namnqani Ahlam A. , Alsaidalani Lama N. , Tawhari Mohammed N. , Badr Omaima I. , Alwafi Hassan
Published: February 2023

Introduction: Obesity is a common comorbidity in patients with asthma and has a significant impact on health and prognoses. However, the extent to which overweight and obesity impact asthma, particularly lung function, remains unclear. This study aimed to report on the prevalence of overweight and obesity and assess their impacts on spirometry parameters in asthmatic patients. Methods: In this multicentre, retrospective study, we reviewed the demographic data and spirometry results of all adult patients with confirmed diagnoses of asthma who visited the studied hospitals’ pulmonary clinics between January 2016 and October 2022. Results: In total, 684 patients with confirmed diagnoses of asthma were included in the final analysis, of whom 74% were female, with a mean ± SD age of 47 ± 16 years. The prevalence of overweight and obesity among patients with asthma was 31.1% and 46.0%, respectively. There was a significant decline in spirometry results in obese patients with asthma compared with patients with healthy weights. Furthermore, body mass index (BMI) was negatively correlated with forced vital capacity (FVC) (L), forced expiratory volume in one second (FEV1), forced expiratory flow at 25–75% (FEF 25–75%) L/s and peak expiratory flow (PEF) L/s (r = −0.22, p < 0.001; r = −0.17, p < 0.001; r = −0.15, p < 0.001; r = −0.12, p < 0.01, respectively). Following adjustments for confounders, a higher BMI was independently associated with lower FVC (B −0.02 [95% CI −0.028, −0.01, p < 0.001] and lower FEV1 (B −0.01 [95% CI −0.01, −0.001, p < 0.05]. Conclusions: Overweight and obesity are highly prevalent in asthma patients, and more importantly, they can reduce lung function, characterised mainly by reduced FEV1 and FVC. These observations highlight the importance of implementing a nonpharmacological approach (i.e., weight loss) as part of the treatment plan for patients with asthma to improve lung function.
Assessment of Complication Risk in the Treatment of Proximal Humerus Fractures: A Retrospective Analysis of 4019 Patients
Authors: Henkelmann Ralf , Hepp Pierre , Mester Bastian , Dudda Marcel , Braun Philipp-Johannes , Kleen Sebastian , Zellner Johannes , Galler Michael , Koenigshausen Matthias , Schildhauer Thomas A. , Saier Tim , Trulson Inga , Dey Hazra Rony-Orijit , Lill Helmut , Glaab Richard , Bolt Basil , Wagner Marcus , Raschke Michael J. , Katthagen Jan Christoph
Published: February 2023

(1) Background: The treatment of proximal humeral fractures (PHFs) is debated controversially. Current clinical knowledge is mainly based on small single-center cohorts. The goal of this study was to evaluate the predictability of risk factors for complications after the treatment of a PHF in a large clinical cohort in a multicentric setting. (2) Methods: Clinical data of 4019 patients with PHFs were retrospectively collected from 9 participating hospitals. Risk factors for local complications of the affected shoulder were assessed using bi- and multivariate analyses. (3) Results: Fracture complexity with n = 3 or more fragments, cigarette smoking, age over 65 years, and female sex were identified as predictable individual risk factors for local complications after surgical therapy as well as the combination of female sex and smoking and the combination of age 65 years or older and ASA class 2 or higher. (4) Conclusion: Humeral head preserving reconstructive surgical therapy should critically be evaluated for patients with the risk factors abovementioned.
COVID-19 Accelerated Cognitive Decline in Elderly Patients with Pre-Existing Dementia Followed up in an Outpatient Memory Care Facility
Authors: Merla Lucia , Montesi Maria Cristina , Ticali Jessica , Bais Bruno , Cavarape Alessandro , Colussi GianLuca
Published: February 2023

Introduction: Coronavirus disease 2019 (COVID-19) may affect the cognitive function and activities of daily living (ADL) of elderly patients. This study aimed to establish the COVID-19 effect on cognitive decline and the velocity of cognitive function and ADL changes in elderly patients with dementia followed up in an outpatient memory care facility. Methods: In total, 111 consecutive patients (age 82 ± 5 years, 32% males) with a baseline visit before infection were divided into those who had or did not have COVID-19. Cognitive decline was defined as a five-point loss of Mini-Mental State Examination (MMSE) score and ADL comprising basic and instrumental ADL indexes (BADL and IADL, respectively). COVID-19 effect on cognitive decline was weighted for confounding variables by the propensity score, whereas the effect on change in the MMSE score and ADL indexes was analyzed using multivariate mixed-effect linear regression. Results: COVID-19 occurred in 31 patients and a cognitive decline in 44. Cognitive decline was about three and a half times more frequent in patients who had COVID-19 (weighted hazard ratio 3.56, 95% confidence interval 1.50–8.59, p = 0.004). The MMSE score lowered on average by 1.7 points/year, independently of COVID-19, but it lowered twice faster in those who had COVID-19 (3.3 vs. 1.7 points/year, respectively, p < 0.050). BADL and IADL indexes lowered on average less than 1 point/year, independently of COVID-19 occurrence. Patients who had COVID-19 had a higher incidence of new institutionalization than those who did not have the disease (45% versus 20%, p = 0.016, respectively). Conclusions: COVID-19 had a significant impact on cognitive decline and accelerated MMSE reduction in elderly patients with dementia.
Bone Mineral Density and All-Cause Mortality in Patients with Nondialysis Chronic Kidney Disease: Results from KNOW-CKD Study
Authors: Suh Sang Heon , Oh Tae Ryom , Choi Hong Sang , Yang Eun Mi , Kim Chang Seong , Bae Eun Hui , Ma Seong Kwon , Oh Kook-Hwan , Hyun Young Youl , Sung Suah , Kim Soo Wan
Published: February 2023

Despite the clear association between low BMD and all-cause mortality in the general population, the association has not been validated in patients with nondialysis CKD. To investigate the association of low BMD with all-cause mortality in this population, a total of 2089 patients with nondialysis CKD at stages 1 to predialysis 5 were categorized into normal BMD (T-score ≥ −1.0), osteopenia (−2.5 < T-score < −1.0), and osteoporosis (T-score ≤ − 2.5) by the BMD at femoral neck. The study outcome was all-cause mortality. Kaplan–Meier curve depicted a significantly increased number of all-cause death events in the subjects with osteopenia or osteoporosis during the follow-up period compared with subjects with normal BMD. Cox regression models demonstrated that osteoporosis, but not osteopenia, was significantly associated with an increased risk of all-cause mortality (adjusted hazard ratio 2.963, 95% confidence interval 1.655 to 5.307). Smoothing curve fitting model visualized a clear inverse correlation between BMD T-score and the risk of all-cause mortality. Even after recategorizing the subjects by BMD T-scores at total hip or lumbar spine, the result was similar to the primary analyses. Subgroup analyses revealed that the association was not significantly modified by clinical contexts, such as age, gender, body mass index, estimated glomerular filtration rate, and albuminuria. In conclusion, low BMD is associated with an increased risk of all-cause mortality in patients with nondialysis CKD. This emphasizes that the routine measurement of BMD by DXA may confer an additional benefit beyond the prediction of fracture risk in this population.
Improved Early Detection Models of Pharyngocutaneous Fistula after Total Laryngectomy
Authors: Heo Yujin , Lee Hyun Suk , Jung Sungha , Lee Changhee , Kim Younghac , Chung Man Ki , Jeong Han-Sin , Baek Chung-Hwan , Ahn Joong Hyun , Son Young-Ik , Choi Nayeon
Published: February 2023

Early detection of pharyngocutaneous fistula (PCF) after total laryngectomy (TL) could prevent severe complications such as major vessel rupture. We aimed to develop prediction models for detecting PCF in the early postoperative period. We retrospectively analyzed patients (N = 263) who received TL between 2004 and 2021. We collected clinical data for fever (>38.0 °C) and blood tests (WBC, CRP, albumin, Hb, neutrophils, lymphocytes) on postoperative days (POD) 3 and 7, and fistulography on POD 7. Clinical data were compared between fistula and no fistula groups, and significant factors were selected using machine learning. Using these clinical factors, we developed improved prediction models for PCF detection. Fistula occurred in 86 (32.7%) patients. Fever was significantly (p < 0.001) more common in the fistula group, and ratios (POD 7 to 3) of WBC, CRP, neutrophils, and neutrophils-to-lymphocytes (NLR) were significantly higher (all p ≤ 0.001) in the fistula group than in the no fistula group. Leakage on fistulography was more common in the fistula group (38.2%) than in the no fistula group (3.0%). The area under curve (AUC) of fistulography alone was 0.68, but predictive models using a combination of fistulography, WBC at POD 7, and neutrophil ratio (POD 7/POD 3) showed better diagnostic performance (AUC of 0.83). Our predictive models may detect PCF early and accurately, which could reduce fatal complications following PCF.
What’s New in the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD)
Authors: Kosmalski Marcin , Frankowski Rafał , Ziółkowska Sylwia , Różycka-Kosmalska Monika , Pietras Tadeusz
Published: February 2023

Non-alcoholic fatty liver disease (NAFLD) is a serious health problem due to its high incidence and consequences. In view of the existing controversies, new therapeutic options for NAFLD are still being sought. Therefore, the aim of our review was to evaluate the recently published studies on the treatment of NAFLD patients. We searched for articles in the PubMed database using appropriate terms, including “non-alcoholic fatty liver disease”, “nonalcoholic fatty liver disease”, “NAFLD”, “diet”, “treatment”, “physical activity”, “supplementation”, “surgery”, “overture” and “guidelines”. One hundred forty-eight randomized clinical trials published from January 2020 to November 2022 were used for the final analysis. The results show significant benefits of NAFLD therapy associated with the use of not only the Mediterranean but also other types of diet (including low-calorie ketogenic, high-protein, anti-inflammatory and whole-grain diets), as well as enrichment with selected food products or supplements. Significant benefits in this group of patients are also associated with moderate aerobic physical training. The available therapeutic options indicate, above all, the usefulness of drugs related to weight reduction, as well as the reduction in insulin resistance or lipids level and drugs with anti-inflammatory or antioxidant properties. The usefulness of therapy with dulaglutide and the combination of tofogliflozin with pioglitazone should be emphasized. Based on the results of the latest research, the authors of this article suggest a revision of the therapeutic recommendations for NAFLD patients.
Early Patient-Triggered Pressure Support Breathing in Mechanically Ventilated Patients with COVID-19 May Be Associated with Lower Rates of Acute Kidney Injury
Authors: Seubert Mark E. , Goeijenbier Marco
Published: February 2023

Background: Acute respiratory distress syndrome (ARDS) in COVID-19 patients often necessitates mechanical ventilation. Although much has been written regarding intensive care admission and treatment for COVID-19, evidence on specific ventilation strategies for ARDS is limited. Support mode during invasive mechanical ventilation offers potential benefits such as conserving diaphragmatic motility, sidestepping the negative consequences of the longer usage of neuromuscular blockers, and limiting the occurrence of ventilator-induced lung injury (VILI). Methods: In this retrospective cohort study of mechanically ventilated and confirmed non-hyperdynamic SARS-CoV-2 patients, we studied the relation between the occurrence of kidney injury and the decreased ratio of support to controlled ventilation. Results: Total AKI incidence in this cohort was low (5/41). In total, 16 of 41 patients underwent patient-triggered pressure support breathing at least 80% of the time. In this group we observed a lower percentage of AKI (0/16 vs. 5/25), determined as a creatinine level above 177 µmol/L in the first 200 h. There was a negative correlation between time spent on support ventilation and peak creatinine levels (r = −0.35 (−0.6–0.1)). The group predominantly on control ventilation showed significantly higher disease severity scores. Conclusions: Early patient-triggered ventilation in patients with COVID-19 may be associated with lower rates of acute kidney injury.
Transperineal Laser Ablation for Benign Prostatic Enlargement: A Systematic Review and Pooled Analysis of Pilot Studies
Authors: Tafuri Alessandro , Panunzio Andrea , De Carlo Francesco , Luperto Elia , Di Cosmo Federica , Cavaliere Arturo , Rizzo Mino , Tian Zhe , Shakir Aliasger , De Mitri Rita , Porcaro Antonio , Cerruto Maria , Antonelli Alessandro , Cormio Luigi , Carrieri Giuseppe , Karakiewicz Pierre , Abreu Andre , Pagliarulo Vincenzo
Published: February 2023

Transperineal laser ablation (TPLA) of the prostate is a new minimally invasive treatment option in men with lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE). The aim of this systematic review was to investigate the efficacy and safety of TPLA in the management of BPE. The primary outcomes were the improvement in urodynamic parameters (maximum urinary flow (Qmax) and postvoiding residue (PVR)) and LUTS relief, assessed using the IPSS questionnaire. The secondary outcomes were the preservation of sexual and ejaculatory functions, assessed with the IEEF-5 and MSHQ-EjD questionnaires, respectively, and rates of postoperative complications. We reviewed the literature for prospective or retrospective studies evaluating the use of TPLA in the treatment of BPE. A comprehensive search in PubMed, Scopus, Web of Science, and ClinicalTrials.gov was performed for English language articles published between January 2000 and June 2022. Pooled analysis of the included studies with available follow-up data for the outcomes of interest was additionally performed. After screening 49 records, six full-text manuscripts were identified, including two retrospective and four prospective non-comparative studies. Overall, 297 patients were included. All the studies independently reported a statistically significant improvement, from baseline, in Qmax, PVR, and IPSS score at each timepoint. Three studies additionally demonstrated that TPLA did not affect sexual function, reporting no change in the IEEF-5 score, and a statistically significant improvement in MSHQ-EjD score at each timepoint. Low rates of complications were recorded in all the included studies. Pooled analysis showed a clinically meaningful improvement in both micturition and sexual outcomes mean values at 1, 3, 6, and 12 months of follow-up, compared with baseline. Transperineal laser ablation of the prostate for the treatment of BPE showed interesting results in pilot studies. However, higher level and comparative studies are needed to confirm its efficacy in relieving obstructive symptoms and preserving sexual function.