bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA Interference (RNAi): An Effective Way to Develop Rational Combination Therapies with Hypomethylating Agents in Acute Leukaemias and Myelodysplastic Syndrome
Authors: Tibes Raoul
Published: January 2023

Therapeutic progress in aggressive myeloid malignancies such as acute myeloid leukaemia (AML), myelodysplastic syndrome (MDS) and advanced myeloproliferative neoplasm (MPNs) has been slow. This is partially due to the heterogeneity of the diseases and the lack of molecular understanding, which delays effective drug development. There will be potentially three rather effective avenues to arrive at novel molecular vulnerabilities that can be therapeutically exploited. First, is identifying disease-specific mutations or other genomic aberrations (i.e. translocations, aberrant methylation) that will result in targeting affected and closely associated genes. Second, is tracing disease evolution over time, clonal evolution by various approaches, many of which will include current genomic tools and assays. Third, a more unbiased, broad discovery approach either with small molecule screens or, in our opinion, by identification of specific molecular vulnerabilities by RNA interference (RNAi). RNAi is a mechanistically rather agnostic high-throughput approach to find essential targets, alone or in combination with commonly used anti-cancer agents. In this paper we will briefly summarise some ideas and early results of RNAi screens, with a focus on hypomethylating agents and how RNAi can identify rational combination therapies with 5-azacytidine that can be rapidly translated into the clinical setting.
Use of HBSAG Quantification To Guide HBIG Prophylaxis After Liver Transplantation
Authors: De Simone Paolo , Carrai Paola , Leonardi Giulia , Silvestri Alessandro , Ghinolfi Davide , Precisi Arianna , Campani Daniela , Filipponi Franco
Published: January 2023

Hepatitis B surface antigen (HBsAg) quantification has recently been introduced to guide treatment in chronic hepatitis B virus (HBV) patients. No information is currently available on use of HBsAg levels to guide HBV immune globulin (HBIG) administration after liver transplantation (LT). We performed a retrospective analysis of a prospectively collected database. Patients were included if: adults (≥18 years); recipients of a primary liver graft; HBsAg-positive and HBV DNA-negative at transplantation; hepatitis C and/or HIV-negative; not transplanted for fulminant hepatic failure; on nucleoside analogues. All patients were administered 30,000 IU HBIG, perioperatively, and hepatitis B surface antibody (HBsAb) was tested at day 7, 14, 28, and monthly thereafter. A further 30,000 HBIG were administered if HBsAb <100 mIU/mL and/or HBsAg >100 IU/mL on day 7. The primary endpoint was the efficacy of HBIG as a percentage of patients achieving HBsAg <100 IU/mL and HBsAb ≥100 mIU/mL at day 7. Secondary endpoints were performance of HBsAg levels in predicting HBsAg loss at day 7, HBV recurrence, graft, and patient survival at last follow-up. 41 LT recipients – transplanted between January 2011 and June 30, 2013 – were included (median age 54 years; male 78%). Hepatocellular carcinoma was present in 24 (58.5%) and hepatitis delta in 19 patients (46.4%); 7 (17.1%) patients did not achieve efficacy at day 7 and wereboosted with additional 30,000 HBIG. A pre-transplant HBsAg level ≥1,000 IU/mL was associated with 60-fold odds for failure at day 7 (p=0.0002). At a median follow-up of 14 months after LT, graft and patient survival were 100% and no case of HBV recurrence had been observed. Based on our results, we advocate the use of HBsAg titre to guide HBIG prophylaxis after LT.
Diagnosis and Management of Occult Hepatitis B Virus Infection: A Short Review
Authors: Martínez González Javier , Lledó Navarro José Luis , Rodríguez de Santiago Enrique , Albillos Martínez Agustín
Published: January 2023

Occult hepatitis B virus infection (OBI) is a challenging clinical entity. It is defined as the presence of viral DNA in the liver or serum of subjects who test negative for the hepatitis B surface antigen. Molecular evidence of OBI consists of covalently closed circular DNA persisting in the nuclei of hepatocytes after infection. Immunocompetent individuals have a lower risk of complications than immunosuppressed subjects. However, under certain scenarios, OBI acquires clinical manifestations that include transmission of the infection via blood or organ transplantation, chronic liver disease progression, hepatocellular carcinoma, and virus reactivation when a state of immunosuppression develops. This review updates the clinical aspects of the diagnosis and management of OBI.
Management of Hepatitis B Virus Infection in Liver Transplant Recipients
Authors: Varghese Joy , Venkataraman Jayanthi , Srinivas Reddy Mettu , Rela Mohamed
Published: January 2023

Hepatitis B virus (HBV)-related liver disease is a common indication for liver transplantation (LT) in Asian countries.1 When left untreated, the overall five-year survival rate in HBV-related cirrhosis is 71%, which in cases of decompensated cirrhosis decreases to 14%.2 In the 1980s, hepatitis B-related acute liver failure and chronic liver disease (CLD) were considered contraindications for LT because of almost universal graft reinfection and high rates of graft and recipient failure (>50%).3-4 These patients had severe and rapidly progressive liver disease with a two-year graft and patient survival of 50% compared to 80% in those transplanted for non-HBV-related CLD.5 As a result, there were fewer LT for HBV liver disease for several years.6 However, with the introduction of nucleoside and nucleotide analogues and the use of intra and post- operative hepatitis B immunoglobulin (HBIG), there was renewed interest in the application of LT in these patients. There was a significant decrease in post-operative HBV recurrence rates.7-9 The current overall survival of patients transplanted for HBV-related cirrhosis has improved to 85% at one year, and 75% at five years.7,10-12 The present review highlights issues pertaining to HBV reinfection and de novo infection in LT recipients with recommendations for its management.
The Ground Is Full of Pitfalls: Association of Chronic Kidney Disease, Conflict Zones, and the Quality of Healthcare in Africa
Authors: Asserraji Mohammed , Bahi Mohammed
Published: January 2023

Public health in sub-Saharan African countries is experiencing a double burden of diseases. First, for decades, these countries have been struggling against infectious diseases. Second, the demographic transition in the area is leading to a rising prevalence of non-communicable diseases (NCDs). Unfortunately, the health systems in sub-Saharan Africa are vulnerable, under-resourced, and unable to address these public health issues. Furthermore, protracted political instability and the consequent conflict zones are worsening the situation. In this short essay, the authors report their real-world experience of providing kidney care for patients with NCDs and chronic kidney disease (CKD) in Bunia, the capital city of the Ituri, a north-eastern district of the Democratic Republic of the Congo (DRC) that has been conflict-ridden for years. In conclusion, there is a lack of evidence and research regarding the heavy burden of NCDs and the appropriate healthcare policy in humanitarian settings such as conflict zones. A co-ordinated, standardised, and evidence-based approach is strongly recommended to reach affected populations in these areas.
Latest ERS Guidelines on non-CPAP Therapies in Obstructive Sleep Apnoea
Authors: Patel Heeral
Published: January 2023

During the European Respiratory Society (ERS) International Congress 2021, speakers discussed the latest updates to the ERS guidelines on non-CPAP therapies in obstructive sleep apnoea. The new recommendations were drawn following a systemic review of the literature.
International Arbitration and Energy Disputes
Authors: Cameron Peter D
Published: January 2023

Arbitration is currently central to the fabric of settling international energy disputes, whether in its commercial or its investment modes. When arbitration is applied to energy disputes, it needs to consider the presence of certain distinct features that can influence the arbitration process. This article identifies and examines eight such features, such as its complexity, scale, duration of projects, their cross-border character, market volatility, strategic concerns, asymmetry, and the pervasive roles of the state. It notes the various efforts at reform of energy arbitration, but argues that such features are likely to strongly influence any regime that evolves from the present one.
Alteration in Biochemical Responses in Leaves of Potato due to Common Scab Disease
Authors: Mahmood Kamra , Sahi Shahbaz T. , Atiq Muhammad , Shahid Muhammad , Ahmed Sohail
Published: January 2023

The current study was designed at the research area of Plant Pathology Research Institute, Ayub Agricultural Research Institute, Faisalabad, Pakistan during 2017– 2020. Fresh leaves of inoculated and un-inoculated potato varieties highly susceptible (FD 76-36), moderately susceptible (FD 73-110), and resistant (Esmee)/ test lines were collected during 2017-18 and 2018-19, at 35, 65 and 95 days after sowing for biochemical analysis.  Superoxide dismutase activity, Catalase activity, Per-oxidase activity, Protein and Total phenolics contents were quantified. FD 76-36 exhibited minimum SOD activity (67.733, 45.637, 24.910) %, followed by FD 73-110 (70.303,57.893, 42.513) % and Esmee (84.567, 65.167, 45.873) % after 35, 65 and 95 days of inoculation respectively as compared to control. FD 76-36 expressed minimum CAT activity (10.990, 7.473, 3.413) %, followed by Esmee (13.537, 9.630, 8.147) % and FD 73-110 (19.277, 8.147, 6.170) % after 35, 65 and 95 days of inoculation respectively as compared to control. FD 76-36 exhibited minimum POD activity (0.2133, 0.2767, 0.3600) %, followed by FD 73-110 (0.2900, 0.5567, 0.6300) % and Esmee (0.8800, 1.2733, 1.5433) % after 35, 65 and 95 days of inoculation respectively as compared to control. FD 76-36 expressed minimum protein contents (3.097, 2.873, 1.260) %, followed by FD 73-110 (7.907, 5.423, 4.267) % and Esmee (12.163, 8.633, 5.127) % after 35, 65 and 95 days of inoculation respectively as compared to control. FD 76-36 expressed minimum TPC (136.31, 115.58, 70.77) %, followed by FD 73-110 (165.85, 136.75, 86.89) % and Esmee (188.42, 158.38, 109.00) % after 35, 65 and 95 days of inoculation respectively as compared to control. The experiment was conducted with a randomized complete block design (RCBD) and three replications. The experimental data were analyzed using Fisher’s analysis of variance technique and treatment means were compared by the least significance difference (LSD) test at a 5% probability level.
Seeing things: The human search for meaningful patterns and the media ecology of computer-generated text
Authors: McDaid John G.
Published: January 2023

Human brains, by evolutionary design, find pattern and impute agency. Computer-generated texts have reached a level of complexity such that we experience them in everyday contexts without interrogating their way of coming to presence, raising concerns that echo critiques by both philosophers and media theorists. This study uses the lens of communication technology as an environment—what Marshall McLuhan called media ecology—to explore understanding and managing the implications of human interaction with such computer-generated texts.
Teaching Informational Competency in a Changing Political Media Environment
Authors: Mathews-Schultz A. Lanethea , Sweet-Cushman Jennie
Published: January 2023

We discuss teaching strategies designed to enhance students’ informational competency. Informational competency shares some of the broad goals of information literacy (IL), including for example, helping students develop the ability to identify, find, evaluate, and produce information. Our concept of informational competency differs in foreground the skills of democratic citizenship outside of the classroom and beyond research activities in the field. Students—citizens—who are informationally competent, not only possess information literacy, but they are also thoughtful curators of political news, intentional and reflective media consumers, and ethical and effective users of social media when it comes to receiving and sharing political information. We discuss strategies to guide students in undergraduate American government courses in cultivating habits of media consumption, developing the skills to evaluate political information and news, and maintaining a healthy skepticism alongside feelings of political trust in a shifting political media landscape.
PELATIHAN PEMASARAN PRODUK KERIPIK CABE MELALUI MEDIA SOSIAL BAGI WARGA ASRAMA BRIMOB BATALYON B MALANG
Authors: Wahyu Ellyn Eka , Oktora Yekie Senja , Hasan Halid , Nurbaya Siti , Widiyowati Eny
Published: January 2023

This Community Service (PPM) activity is carried out as a responsibility in fulfilling the obligations of the Tri Dharma of Higher Education. The target objects in this PPM activity are women from the Asrama Brimob Batalyon B Pelopor, Kelurahan Ampeldento, Kecamatan Pakis,  Kabupaten Malang. This PPM activity seeks to provide understanding through materials and guidance to promote the sale of chili chips using social media. This guidance is given to the public through material presentation activities and hands-on practical activities on how to create written and photo content which will later be used as material to promote chili chips products so that they are expected to get customers outside the Asrama Brimob Ampeldento. From this Community Service (PPM) activity, it is hoped that a synergy will be created between the women of the Asrama Brimob Batalyon B Pelopor Kabupaten Malang and the Malang State Polytechnic, that this guidance activity can help partners in increasing their income through promotional activities and sales of chili chips by use social media continuously.
PELATIHAN KEWIRAUSAHAAN PEMBUATAN MINUMAN THAI TEA DAN PERHITUNGAN HARGA POKOK PRODUKSI PADA IBU-IBU PKK RT 2 RW 5 PERUMAHAN MUARA SARANA INDAH JETIS MULYOAGUNG DAU MALANG
Authors: Indrayati Indrayati , Ludfi Djajanto  , Basuki Rachmat  , Kuni Utami  , Suryadi
Published: January 2023

Entrepreneurship Training in making Thai Tea and calculation of the cost of production is one of the efforts to provide knowledge for PKK mothers to improve nutrition or endurance as well as increase income for PKK mothers in Muara Sarana Indah housing Mulyoagung Dau Malang. This effort to improve nutrition is the responsibility of universities, especially Malang State Polytechnic in order to increase endurance by making their own processed food at a lower cost. This PKM was carried out on August  14 and 15, 2021.
LITERASI FITUR DATA-FORM MS. EXCEL UNTUK MENGELOLA DATABASE ANGGOTA PERKUMPULAN KEMATIAN “LAZARUS” MALANG
Authors: Wardani Tri Istining , Rachmi Asminah , Sudjanarti Dwi , Khabibah Umi , Zaini Achmad
Published: January 2023

This community service aims to develop technical skills in managing databases. So far, the “Lazarus" commission processed all regular membership fees manually. The repetitive work and recording errors happened along the way.  With a total of 428 family members out of 993, the above data processing was inefficient and ineffective.

Ms. Excel, especially the Data-Form feature will make database management easier for someone to process data entry, edit, search, and delete in a database table. When a database has been formed, the preparation of the annual report will also be able to be compiled efficiently & effectively, because the database is already stored in a soft file.

Community service is carried out through training assistance. The activity begins with preparing teaching modules, followed by assisting to create a table model database in Ms. Excel. Subsequently, design a Data (Entry) Form model for recapitulation.

The competencies have been achieved because in the end the database management has been simulated very well using real data & problems. Therefore, the final evaluation results declared that the database management model uses the Data Form successfully to help the "Lazarus" commission maximize its service.
How Does Song of Moses in the Exodus 15:8-14, Teach Education? (LXX-Rahlfs)
Authors: Chia Philip Suciadi , Juanda Juanda
Published: January 2023

There are various ways to teach people to be able to hope and rely on God. Behold, LORD, who among the gods is like you? Who is like you, wonderful in holiness? Who can work miracles and mighty acts like yours? This article argues that the song of Moses teaches the faith lesson. The miracle of God brings healing and comfort. Therefore, God’s deliverance should encourage the people of God to trust the Lord more in their difficulties.
ОСОБЕННОСТИ ФИЗИЧЕСКОГО И ФУНКЦИОНАЛЬНОГО СОСТОЯНИЯ ЖЕНЩИН С ВЫСОКИМ УРОВНЕМ СТРЕССА В ПЕРИОД МЕНОПАУЗЫ
Authors: Захарьева Наталья , Комкова Мария
Published: January 2023

The article examines the features of the physical and functional state of women during menopause, examines the risks of developing physical and psychological stress during the period of hormonal changes and their relationship with climacteric syndrome. The interrelation of the predisposition of the development of climacteric syndrome with the BMI indicators, the type of physique and the level of fitness of the body of women is revealed.
Symptom's resolution and growth outcome of children with cow's milk protein allergy consuming two hydrolyzed formulas: A retrospective study in Mexico
Authors: Estrada Reyes Elizabeth , Zepeda Ortega Benjamín , ten Haaf Dominique , Kudla Urszula , Muhardi Leilani , Hofman Denise L. , Hageman Jeske H. J. , Huerta Hernández Rosa E.
Published: January 2023

Background

Cow's milk protein allergy (CMPA) is the leading cause of food allergy in infants and young children. An extensively hydrolyzed formula (eHF) is the first choice of dietary management, however, not all of them have similar peptide profiles and degree of hydrolysis. The aim of this retrospective study was to investigate the use of two commercially available infant formulas in the clinical management of CMPA in Mexico in terms of symptoms' resolution and growth trajectories.

Methods

Medical records of 79 subjects from four sites in Mexico were included to retrospectively evaluate the trajectory of atopic dermatitis, other symptoms of cow's milk protein allergy and growth outcomes. The study formulas were based on hydrolyzed whey protein (eHF-W) and hydrolyzed casein protein (eHF-C).

Results

Medical records of 79 patients were enrolled, 3 were excluded from analysis based on previous formula consumption. Seventy-six children with confirmed CMPA based on skin prick test and/or serum specific IgE levels were included in the analysis. 82% of patients (n = 65) consumed the eHF-C, reflecting the doctors' preference for formulas with a higher grade of hydrolysis and the high incidence of positive reactions to beta-lactoglobulin amongst subjects. During their first visit to the doctors, 55% of the subjects consuming the casein-based formula and 45% of subjects consuming the whey-based formula presented with mild or moderate dermatological symptoms. Other frequently reported symptoms included respiratory issues, enteropathies and colitis which improved during the consumption of both formulas. All CMPA-related symptoms showed improvement during formula consumption. During the period of retrospective observation, growth significantly improved for both groups.

Conclusion

Consumption of eHF-C and eHF-W effectively improved symptoms' resolution and growth outcomes among children with CMPA in Mexico. More preference was reported towards eHF-C due to its hydrolysate profile and lack of b-lactoglobulin.

Trial registration

The study was registered at ClinicalTrials.gov: NCT04596059.
High-speed predictions of post-burn contraction using a neural network trained on 2D-finite element simulations
Authors: Egberts Ginger , Vermolen Fred , van Zuijlen Paul
Published: January 2023

Severe burn injuries often lead to skin contraction, leading to stresses in and around the damaged skin region. If this contraction leads to impaired joint mobility, one speaks of contracture. To optimize treatment, a mathematical model, that is based on finite element methods, is developed. Since the finite element-based simulation of skin contraction can be expensive from a computational point of view, we use machine learning to replace these simulations such that we have a cheap alternative. The current study deals with a feed-forward neural network that we trained with 2D finite element simulations based on morphoelasticity. We focus on the evolution of the scar shape, wound area, and total strain energy, a measure of discomfort, over time. The results show average goodness of fit (R2) of 0.9979 and a tremendous speedup of 1815000X. Further, we illustrate the applicability of the neural network in an online medical app that takes the patient's age into account.
Safety and efficacy of clinical-grade, cryopreserved menstrual blood mesenchymal stromal cells in experimental acute respiratory distress syndrome
Authors: Alcayaga-Miranda Francisca , Dutra Silva Johnatas , Parada Nicol , Andrade da Silva Luisa Helena , Ferreira Cruz Fernanda , Utreras Yildy , Hidalgo Yessia , Cádiz María Ignacia , Tapia Limonchi Rafael , Espinoza Francisco , Bruhn Alejandro , Khoury Maroun , R. M. Rocco Patricia , Cuenca Jimena
Published: January 2023

Background: Treatment for critical care conditions, such as acute respiratory distress syndrome (ARDS), requires ready-to-administer injectable mesenchymal stromal cells (MSCs). A validated cryopreserved therapy based on MSCs derived from menstrual blood (MenSCs) is an attractive option that offers advantages over freshly cultured cells and allows its use as an off-the-shelf therapy in acute clinical conditions. The main goal of this study is to provide evidence on the impact of cryopreservation on different biological functions of MenSCs and to determine the optimal therapeutic dose, safety, and efficacy profile of clinical-grade, cryopreserved (cryo)-MenSCs in experimental ARDS.

Methods: Biological functions of fresh versus cryo-MenSCs were compared in vitro. The effects of cryo-MenSCs therapy were evaluated in vivo in ARDS-induced (Escherichia coli lipopolysaccharide) C57BL/6 mice. After 24 h, the animals were treated with five doses ranging from 0.25×105 to 1.25×106 cells/animal. At 2 and 7 days after induction of ARDS, safety and efficacy were evaluated.

Results: Clinical-grade cryo-MenSCs injections improved lung mechanics and reduced alveolar collapse, tissue cellularity, and remodelling, decreasing elastic and collagen fiber content in alveolar septa. In addition, administration of these cells modulated inflammatory mediators and promoted pro-angiogenic and anti-apoptotic effects in lung-injured animals. More beneficial effects were observed with an optimal dose of 4×106 cells/Kg than with higher or lower doses.

Conclusion: From a translational perspective, the results showed that clinical-grade cryopreserved MenSCs retain their biological properties and exert a therapeutic effect in mild to moderate experimental ARDS. The optimal therapeutic dose was well-tolerated, safe, and effective, favouring improved lung function. These findings support the potential value of an off-the-shelf MenSCs-based product as a promising therapeutic strategy for treating ARDS.
Half sandwich-type osmium, ruthenium, iridium and rhodium complexes with bidentate glycosyl heterocyclic ligands induce cytostasis in platinum-resistant ovarian cancer cells and bacteriostasis in Gram-positive multiresistant bacteria
Authors: Kacsir István , Sipos Adrienn , Kiss Tímea , Major Evelin , Bajusz Nikolett , Tóth Emese , Buglyó Péter , Somsák László , Kardos Gábor , Bai Péter , Bokor Éva
Published: January 2023

The toxicity of and resistance to platinum complexes as cisplatin, oxaliplatin or carboplatin calls for the replacement of these therapeutic agents in clinical settings. We have previously identified a set of half sandwich-type osmium, ruthenium and iridium complexes with bidentate glycosyl heterocyclic ligands exerting specific cytostatic activity on cancer cells but not on non-transformed primary cells. The apolar nature of the complexes, conferred by large, apolar benzoyl protective groups on the hydroxyl groups of the carbohydrate moiety, was the main molecular feature to induce cytostasis. We exchanged the benzoyl protective groups to straight chain alkanoyl groups with varying length (3 to 7 carbon units) that increased the IC50value as compared to the benzoyl-protected complexes and rendered the complexes toxic. These results suggest a need for aromatic groups in the molecule. The pyridine moiety of the bidentate ligand was exchanged for a quinoline group to enlarge the apolar surface of the molecule. This modification decreased the IC50value of the complexes. The complexes containing [(η6-p-cymene)Ru(II)], [(η6-p-cymene)Os(II)] or [(η5-Cp*)Ir(III)] were biologically active unlike the complex containing [(η5-Cp*)Rh(III)]. The complexes with cytostatic activity were active on ovarian cancer (A2780, ID8), pancreatic adenocarcinoma (Capan2), sarcoma (Saos) and lymphoma cell lines (L428), but not on primary dermal fibroblasts and their activity was dependent on reactive oxygen species production. Importantly, these complexes were cytostatic on cisplatin-resistant A2780 ovarian cancer cells with similar IC50values as on cisplatin-sensitive A2780 cells. In addition, the quinoline-containing Ru and Os complexes and the short chain alkanoyl-modified complexes (C3 and C4) proved to be bacteriostatic in multiresistant Gram-positiveEnterococcusandStaphylococcus aureusisolates. Hereby, we identified a set of complexes with submicromolar to low micromolar inhibitory constants against a wide range of cancer cells, including platinum resistant cells and against multiresistant Gram-positive bacteria.
Therapeutic targeting of mineralocorticoid receptors in pulmonary hypertension: Insights from basic research
Authors: Mamazhakypov Argen , Lother Achim
Published: January 2023

Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling and associated with adverse outcomes. In patients with PH, plasma aldosterone levels are elevated, suggesting that aldosterone and its receptor, the mineralocorticoid receptor (MR), play an important role in the pathophysiology of PH. The MR plays a crucial role in adverse cardiac remodeling in left heart failure. A series of experimental studies from the past few years indicate that MR activation promotes adverse cellular processes that lead to pulmonary vascular remodeling, including endothelial cell apoptosis, smooth muscle cell (SMC) proliferation, pulmonary vascular fibrosis, and inflammation. Accordingly, in vivo studies have demonstrated that pharmacological inhibition or cell-specific deletion of the MR can prevent disease progression and partially reverse established PH phenotypes. In this review, we summarize recent advances in MR signaling in pulmonary vascular remodeling based on preclinical research and discuss the potential, but also the challenges, in bringing MR antagonists (MRAs) into clinical application.
A regime shift in North Pacific annual mean sea surface temperature in 2013/14
Authors: Xiao Dong , Ren Hong-Li
Published: January 2023

This study revealed a new regime shift in the North Pacific annual mean sea surface temperature (SST) in 2013/14, robust in multiple SST data sets. This regime shift shows a horseshoe pattern with warming SST along the North American western coast and toward the Central Pacific. It suggests a phase reversal of the Victoria Mode (VM) and it seems unrelated to the shift in the Pacific Decadal Oscillation (PDO) and Interdecadal Pacific Oscillation (IPO). Associated with this regime shift, the annual surface air temperature significantly enhanced over the high-latitude landmass after 2014, whereas it declined over northeastern Canada and southwestern Greenland. The annual precipitation generally increased (decreased) in the Northern (Southern) Hemisphere landmass monsoon regions. There are no regime shifts in Equatorial Central-East Pacific SST and the intensity and locations of the Aleutian Low around 2013/14. These facts suggest the regime shift of North Pacific SST in 2013/14 may not originate from the decadal variations of the midlatitude atmosphere and tropical ocean. The extensive influence of this regime shift in 2013/14 on the atmospheric, oceanic and ecological systems warrants further investigation.
Post-lacustrine evolution of a tectonically-controlled intermontane basin: Drainage network analysis of the Mercure basin, southern Italy
Authors: Gioia Dario , Corrado Giuseppe , Danese Maria , Minervino Amodio Antonio , Schiattarella Marcello
Published: January 2023

Topographic analysis, drainage network morphometry, river profile analysis, and spatial distribution of fluvio-lacustrine terraces have been used to reconstruct the drainage network evolution in the Mercure River basin, a large intermontane tectonic basin of the axial zone of southern Apennines. Morphotectonic evolution of the study area is mainly controlled by poly-kinematics high-angle WNW-ESE and NE-SW faults, which promoted the development of a complex landscape with relict landscapes and/or low-relief erosional surfaces that occurred in a staircase arrangement at the top of the landscapes or at higher altitudes than the basin infill. The creation of the accommodation space for the deposition of the thick basin infill was related to an important tectonic phase of block-faulting along N120°-trending normal faults, which occurred in the final part of the Lower Pleistocene. Such an evolution strongly controls the longitudinal profile forms of channels draining the northern sector of the study area, which are featured by a well-developed concave-up segment in river profiles of these channels between an upward trait with lower values of channel steepness and the trace of the master fault. River profiles in north-western and south-east sectors of the Mercure River basin exhibit clear knickpoints at altitudes comparable with those of the superimposed orders of relict landscapes related to the initial formation of the tectonic basin and the subsequent evolution of the endorheic basin, with a post-lacustrine geomorphological evolution of the drainage network that is controlled by fluvial incision occurring at rates comparable than those reconstructed by independent morphotectonic markers. The erosion of the threshold of the endorheic basin occurring during the base-level fall of the MIS 12 promoted a dramatic base-level fall of about 150 m, which corresponds to a mean incision rate of about 0.35 mm/yr. Post-lacustrine evolution of the Mercure basin strongly controls the morphometric features of the drainage network, which preserves a centripetal pattern with several planimetric anomalies such as counterflow and high-angle confluences, local-scale fluvial capture phenomena and drainage divide migrations.
Dynamic changes in forest cover and human activities during the Holocene on the northeast Tibetan plateau
Authors: Wende Zhuoma , Hou Guangliang , Chen Hongming , Jin Sunmei , Zhuoma Lancuo
Published: January 2023

Human activities strongly influenced the present-day environment of the Tibetan Plateau, especially in the northeastern area. The questions over when and to what extent humans began to utilize the plateau environment have been long investigated, but there are still gaps in our understanding, such as the relationship between forest dynamics and anthropogenic activities. Here, we simulate the potential Holocene geographical distribution of the three dominant coniferous species in the Northeast Tibetan Plateau in response to climate/environment and analyze pollen records and multi-proxies for anthropogenic activities to explore human impact on natural forest dynamics. Simulation results show marked expansion of Picea and Pinus coniferous forests in the Early Holocene (11.5–8.3 ka BP), continuing into the Mid Holocene (8.3–4.0 ka BP). However, there was a slight contraction of forest in the Late Holocene (4.0–2.6 ka BP) in the western part of the region, and near disappearance in the eastern Qaidam Basin, although both Pinus and Picea slightly increased in Hehuang Valley. Pollen analysis confirms the patterns, with an increase in arboreal pollen mainly comprising Pinus and Picea from Early to Early Mid Holocene (11.5–5.3 ka BP), followed by a decrease. Proxies of anthropogenic activities, including carbon concentration, archeological sites, and, synanthropic plants, increased significantly after 5.3 ka BP, with archeological evidence for intensive exploitation of forest and turnover of natural vegetation. We argue that forest retreat at 5.3–4.0 ka BP was due to the expansion of cropland and increasing demand for wood. Significant coniferous forest retreat and degradation from 4.0 to 2.6 ka BP, with forest succession in Hehuang Valley, was driven by the booming population, extensive grazing, and forest exploitation; the drying cooling climate may have aggravated the pace of deforestation at higher elevations. This study presents new insights into the deforestation on the Northeast Tibetan Plateau in the Holocene.
Clinical effectiveness of second-line antihyperglycemic drugs on major adverse cardiovascular events: An emulation of a target trial
Authors: Siriyotha Sukanya , Lukkunaprasit Thitiya , Angkananard Teeranan , Looareesuwan Panu , McKay Gareth J. , Attia John , Thakkinstian Ammarin
Published: January 2023

Introduction

The cardiovascular benefits of multiple antihyperglycemic drugs as add-on therapies to metformin in the real-practice are unclear. This study aimed to directly compare major adverse cardiovascular events (CVE) associated with these multiple drugs.

Methods

An emulation of a target trial was conducted using a retrospective-cohort data of type 2 diabetes mellitus (T2DM) prescribed with second-line drugs on top of metformin, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), thiazolidinediones (TZD) and sulfonylureas (SUs). We applied inverse probability weighting and regression adjustment using intention-to-treat (ITT), per-protocol analysis (PPA) and modified ITT. Average treatment effects (ATE) were estimated using SUs as the reference.

Results and Discussion

Among 25,498 patients with T2DM, 17,586 (69.0%), 3,261 (12.8%), 4,399 (17.3%), and 252 (1.0%) received SUs, TZD, DPP4i, and SGLT2i. Median follow-up time was 3.56 (1.36-7.00) years. CVE was identified in 963 patients. The ITT and modified ITT approaches showed similar results; the ATE (i.e., the difference of CVE risks) for SGLT2i, TZD, and DPP4i compared to SUs were -0.020(-0.040, -0.0002), -0.010(-0.017, -0.003), and -0.004(-0.010, 0.002), respectively, indicating 2% and 1% significant absolute risk reduction in CVE in SGLT2i and TZD compared to SUs. These corresponding effects were also significant in the PPA with ATEs of -0.045(-0.060, -0.031), -0.015(-0.026, -0.004), and -0.012(-0.020, -0.004). In addition, SGLT2i had 3.3% significant absolute risk reduction in CVE relative to DPP4i. Our study demonstrated benefits of SGLT2i and TZD in reducing CVE in T2DM patients compared to SUs when added to metformin.
Low-temperature nuclear heating reactors: Characteristics and application of licensing law in China
Authors: Liu Bingyu , Liu Jiu , Shen Le
Published: January 2023

As one type of small modular nuclear reactor (SMR), the low-temperature nuclear heating reactors (LTNHRs), which have the characteristics of small size, a large power ratio, and good adaptability, can help provide energy in winter as well as reduce greenhouse gas emissions. Despite a growing number of LTNHRs worldwide, a mature legal regulatory system specifically targeting LTNHRs remains undeveloped. Further, few discussions have focused on the prospect of regulating LTHHRs and how national and international frameworks can respond to the new and increasing development of LTNHRs. Given the growing prominence of LTNHRs, this article aims to fill in the research gap by exploring possible regulatory pathways for LTNHRs and whether the existing nuclear regulatory frameworks developed for large reactors could be sufficiently applied to LTNHRs. The article examines and analyzes the prospects and potential challenges for regulating LTHHRs, specifically in the field of licensing. In particular, the article takes the Chinese nuclear legal system as an example to analyze whether the existing legislation and regulations can meet the new requirements for licensing of LTNHRs—given their unique characteristics—in China. Finally, this article proposes suggestions to address the obstacles to regulating LTNHRs, including amending the existing international regulatory framework, improving licensing supervision throughout environmental assessment and public participation, and strengthening international legal cooperation, to ensure the robust and reasonable development of LTNHRs worldwide.
Battery energy scheduling and benefit distribution models under shared energy storage: A mini review
Authors: Kong Shaohua , Wang Yuchen , Xie Dongwei
Published: January 2023

Energy storage solutions are strategically important for achieving carbon neutrality and carbon peaking goals. However, high installation costs, demand mismatch, and low equipment utilization have prevented the large-scale commercialization of traditional energy storage. The shared energy storage mode that relies on sharing economy can effectively overcome these problems and has recently attracted widespread attention. In this mini-review, firstly, the concept of shared energy storage is discussed and its application in different countries is illustrated. Second, two core issues in the shared energy storage research—optimal energy scheduling and rational profit distribution—are sorted out and the common modeling approaches and solving algorithms are summarized. Additionally, the dilemma of balancing energy efficiency with distribution fairness faced by the practical application of shared energy storage is pointed out. On this basis, blockchain technology is pointed out to solve the above dilemma of shared energy storage and key directions are given for future research.
Attainment of Zero Emission Targets by Transition Towards sustainable development of value of creative products
Authors: Wang Jian , Zhou Min
Published: January 2023

Wind, hydropower, solar, and other renewable energy (RE) replace conventional energy sources when the global green and low-carbon transition is broadly considered. Therefore, the current study investigates the core determinants of renewable energy development (RED) in China from 1990 to 2020: carbon emissions efficiency (CEE), green finance (GF), urbanization (URB), openness (Op), and gross domestic product (GDP). However, advanced econometric techniques are used to investigate the desired objectives, such as an interactive fixed effects panel test, threshold panel regression, Pooled Mean Group, and Bootstrap Panel causality test. The research findings shows a negative association of CEE with renewable energy development. According to these findings, which are in line with the optimization method, it seems that RED is doing an outstanding job of reaching carbon neutrality. However, there found an increase in RED via green finance and economic growth over time. Also, a negative relationship exists between urbanization and openness with energy development. In comparison, zero-emission competition is expected to reshape the globe’s demographics.
Omics approaches to understanding the efficacy and safety of disease-modifying treatments in multiple sclerosis
Authors: Lorefice Lorena , Pitzalis Maristella , Murgia Federica , Fenu Giuseppe , Atzori Luigi , Cocco Eleonora
Published: January 2023

From the perspective of precision medicine, the challenge for the future is to improve the accuracy of diagnosis, prognosis, and prediction of therapeutic responses through the identification of biomarkers. In this framework, the omics sciences (genomics, transcriptomics, proteomics, and metabolomics) and their combined use represent innovative approaches for the exploration of the complexity and heterogeneity of multiple sclerosis (MS). This review examines the evidence currently available on the application of omics sciences to MS, analyses the methods, their limitations, the samples used, and their characteristics, with a particular focus on biomarkers associated with the disease state, exposure to disease-modifying treatments (DMTs), and drug efficacies and safety profiles.
A rare case of IgG4-related disease masquerading as periurethral malignancy and review of the literature
Authors: Zeng Zhiru , Gao Shasha , Lu Xiaoyong
Published: January 2023

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disease that typically manifests as mass lesions affecting almost any organ including the pancreas, lacrimal and salivary glands, liver, lung and kidney. However, IgG4-RD with urethra involvement is scarce. We describe a rare case of IgG4-RD involving the urethra mimicking urethral carcinoma and review the published literature. A 64-years-old female presented with progressive dysuria for more than 2 months. Pelvic gadolinium-enhanced magnetic resonance imaging revealed a huge mass encasing the urethra which showed obvious enhancement in the arterial phase. And contrast-enhanced ultrasound showed that the entire mass was heterogeneously enhanced and displayed a fast-forward and fast-out pattern, which was highly suggestive of malignant tumor. The diagnosis of IgG4-RD was finally established by ultrasound-guided transvaginal mass needle biopsy. The patient was treated with methylprednisolone and cyclophosphamide and dysuria disappeared in the first week of therapy. She has been followed up in our clinic for 1 year without recurrence. The diagnosis of IgG4-RD should be considered in the differential diagnosis of a periurethral mass. Ultrasound-guided transvaginal mass needle biopsy is a safe and well-established tissue sampling method and should be performed in order to avoid unnecessary surgery.
Transcriptomic analysis reveals the potential crosstalk genes and immune relationship between IgA nephropathy and periodontitis
Authors: Gao Xiaoli , Guo Ziyi , Wang Pengcheng , Liu Zhiqiang , Wang Zuomin
Published: January 2023

Background

It is well known that periodontitis has an important impact on systemic diseases. The aim of this study was to investigate potential crosstalk genes, pathways and immune cells between periodontitis and IgA nephropathy (IgAN).

Methods

We downloaded periodontitis and IgAN data from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify shared genes. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the shared genes. Hub genes were further screened using least absolute shrinkage and selection operator (LASSO) regression, and a receiver operating characteristic (ROC) curve was drawn according to the screening results. Finally, single-sample GSEA (ssGSEA) was used to analyze the infiltration level of 28 immune cells in the expression profile and its relationship with shared hub genes.

Results

By taking the intersection of WGCNA important module genes and DEGs, we found that the SPAG4, CCDC69, KRT10, CXCL12, HPGD, CLDN20 and CCL187 genes were the most important cross-talk genes between periodontitis and IgAN. GO analysis showed that the shard genes were most significantly enriched in kinase regulator activity. The LASSO analysis results showed that two overlapping genes (CCDC69 and CXCL12) were the optimal shared diagnostic biomarkers for periodontitis and IgAN. The immune infiltration results revealed that T cells and B cells play an important role in the pathogenesis of periodontitis and IgAN.

Conclusion

This study is the first to use bioinformatics tools to explore the close genetic relationship between periodontitis and IgAN. The SPAG4, CCDC69, KRT10, CXCL12, HPGD, CLDN20 and CCL187 genes were the most important cross-talk genes between periodontitis and IgAN. T-cell and B-cell-driven immune responses may play an important role in the association between periodontitis and IgAN.
Inflammation and autoimmune myasthenia gravis
Authors: Huda Ruksana
Published: January 2023

Myasthenia gravis (MG) is a neuromuscular autoimmune disorder characterized by chronic but intermittent fatigue of the eye- and general body muscles. Muscle weakness is caused primarily by the binding of an autoantibody to the acetylcholine receptors, resulting in blockage of normal neuromuscular signal transmission. Studies revealed substantial contributions of different proinflammatory or inflammatory mediators in the pathogenesis of MG. Despite these findings, compared to therapeutic approaches that target autoantibody and complements, only a few therapeutics against key inflammatory molecules have been designed or tested in MG clinical trials. Recent research focuses largely on identifying unknown molecular pathways and novel targets involved in inflammation associated with MG. A well-designed combination or adjunct treatment utilizing one or more selective and validated promising biomarkers of inflammation as a component of targeted therapy may yield better treatment outcomes. This review briefly discusses some preclinical and clinical findings of inflammation associated with MG and current therapy approaches and suggest the potential of targeting important inflammatory marker(s) along with current monoclonal antibody or antibody fragment based targeted therapies directed to a variety of cell surface receptors.
The potential climatic range of spotted lanternfly may be broader than previously predicted
Authors: Keena Melody A. , Hamilton George , Kreitman Devin
Published: January 2023

Spotted lanternfly (Lycorma delicatula White) is an invasive planthopper that was introduced to the United States from Asia and readily spreads via human aided means. Three geographically separated populations in the United States (NJ, PA, and WV) were collected and used to assess the effects of fluctuating thermal regimes that included temperatures above or below the upper (Tmax) and lower (Tmin) developmental thresholds, respectively, on nymphal survival and development, and to determine if there was within- and among-population variation in hatch timing and temperature responses of nymphs. Nymphs exposed to temperatures > Tmax and <Tmin were able to develop when those temperatures were part of an alternating regime, even though development took longer, and the average survival was lower than that of the corresponding constant temperature. When individuals from different geographically separated populations were exposed to the same temperature regimes, there was intra- and inter-population variation in time to hatch, instar duration, and estimated Tmin values. The NJ population on average hatched earlier than the PA populations. There was 1-4°C difference in estimates of the Tmin for the first through third instars for individuals from different populations. In addition, the time in instar estimates for constant 15 and 25°C from this study were 26 and 7 days faster, respectively, than estimates from previous studies. The variability in thermal responses documented in this study is large enough to have impacts on predicted phenology and potential risk of establishment especially in areas previously considered too cold to be at risk. This new information should be incorporated into phenology and risk models to improve their predictive ability.