bluuebunny/crossref_metadata_2025 huggingface dataset:
Socioeconomic disparities in fertility treatments and associated likelihood of livebirth following In Vitro Fertilization
Authors: Manvelyan Evelina , Abittan Baruch , Weiwei Shan , Shahani Disha , Kwait Brittany , Rausch Mary , Blitz Matthew
Published: January 2023

Objective: To determine whether neighborhood-level socioeconomic characteristics are associated with the likelihood of livebirth (LB) following in vitro fertilization (IVF). Specifically, we evaluated neighborhood-level household income, unemployment rate, and educational attainment.
Design: A retrospective cross-sectional study was conducted for patients undergoing autologous IVF cycles.
Setting: Large academic health system.
Interventions: For each patient, ZIP code of residence was used as a proxy for neighborhood. Neighborhood characteristics were compared between patients with and without LB. Generalized estimating model was used to adjust the association between SES factors and likelihood of a live birth with respect to relevant clinical factors.
Results: A total of 4,942 autologous IVF cycles from 2,768 patients were included: 1,717 (62.0%) had at least one associated LB. Patients who achieved LB from IVF were younger, had higher anti-Mullerian hormone (AMH) levels, lower body mass index (BMI), and differed by ethnic background, primary language, and neighborhood socioeconomic characteristics. In a multivariable model, language, age, AMH, and BMI were associated with a live birth from IVF. None of the neighborhood-level socioeconomic variables were associated with the total number of IVF cycles or cycles required to achieve first LB.
Conclusion: Patients living in neighborhoods with lower annual household income have
lower odds of livebirth after IVF compared to those living in more affluent areas, despite undergoing the same number of IVF stimulation cycles.
What is the role of CHCHD2 in adrenal tumourigenesis?
Authors: Karapanagioti Angeliki , Nasiri-Ansari Narjes , Moustogiannis Athanasios , Trigas George C , Zografos Georgios , Aggeli Chrysanthi , Kyriakopoulos Georgios , Choreftaki Theodosia , Philippou Anastassios , Kaltsas Gregory , Kassi Eva , Angelousi A
Published: January 2023

Purpose
CHCHD2 is an anti-apoptotic mitochondrial protein acting through the BCL2/BAX pathway in various cancers. However, data on the regulatory role of CHCHD2 in adrenal tumourigenesis are scarce.
Methods
We studied the expression of CHCHD2, BCL2 and BAX in human adrenocortical tissues and SW-13 cells. mRNA and protein levels were analysed through qPCR and immunoblotting respectively in 16 benign adrenocortical neoplasms (BANs) and 10 adrenocortical carcinomas (ACCs) along with the adjacent normal adrenal tissues (controls). BCL2/BAX mRNA expression was also analyzed in SW-13 cells after CHCHD2 silencing. MTS, flow cytometry and scratch assays were performed to assess cell viability, apoptosis and invasion respectively.
Results
BCL2 and CHCHCD2 mRNA and protein expression was increased in BANs compared with normal adrenal tissues whereas BAX was decreased. BAX and CHCHD2 mRNA and protein levels were significantly down-regulated and up-regulated respectively in ACCs compared to either BANs or controls. Expression of the studied genes was not different among cortisol-secreting and non-functional ACAs. No significant association was found between genes’ expression and established prognostic markers of ACCs patients. In-vitro analysis showed that CHCHD2 silencing resulted in reduced cell viability and invasion as well as increased SW-13 cells apoptosis.
Conclusions
CHCHD2 expression seems to be implicated in adrenal tumourigenesis through BAX/BCL2 pathway similarly to other tumours. However, the exact mechanism needs to be further studied along with the possibility of being a potentional therapeutic target.
Comparison of pregnancy rates in antagonist cycles after luteal support with GnRH-agonist versus progesterone – prospective randomized study
Authors: Buhbut Eadit , Nabulsi Rinad , Avigdor Gilad , Ben-Ami Ido
Published: January 2023

Purpose: To compare pregnancy rates in GnRH-antagonist cycles triggered with hCG after luteal phase support with intranasal GnRH agonist as sole luteal phase support versus standard vaginal progesterone preparation.
Methods: Prospective randomized controlled study of patients who underwent antagonist-based IVF cycles triggered with hCG at university-affiliated tertiary medical center between 2020 and 2022. Patients meeting the inclusion criteria were randomly assigned to either intranasal GnRH-agonist or vaginal progesterone for luteal phase support. Pregnancy rates were the main outcome compared between the two study groups.
Results: A total of 150 patients underwent 164 cycles, 127 cycles of which were included in the study cohort. Of them, 64 (50.4%) and 63 (49.6%) cycles were treated with GnRH-agonist or progesterone respectively as sole luteal phase support. A significantly higher pregnancy rate was demonstrated in the GnRH-agonist group compared with the progesterone group. After adjustment of several potential confounders such as age, body mass index, past obstetric history, number of IVF cycles, oocyte retrieved and embryos transferred, GnRH-agonist was still associated with a higher pregnancy rate (odds ratio 3.4, 95% confidence interval 1.4-8.3). Ovarian hyperstimulation syndrome rates were similar between the groups.
Conclusions: This prospective study suggests that nasal GnRH-agonist for luteal phase support is associated with higher pregnancy rates compared with standard progesterone support in an antagonist-based protocol triggered with hCG, while maintaining a similar safety profile.
Slip-oscillate response in a synchronizing nonlinear micro-resonator
Authors: Shi Zhan , Pu Dong , Wang Xuefeng , Wei Xueyong , Huan Ronghua
Published: January 2023

Synchronization in phase feedback micro/nano systems are widely delved for its rich dynamics and prospective applications. As a key factor that affects the sensory performance, the synchronization transient process deserves much focus while few investigations on it so far. Here, we report the observation of the slipping and oscillation behavior of the frequency and phase of a nonlinear micro-oscillator injected by a harmonic perturbation in the synchronization region. The observed frequency and phase of the oscillator not monotonically approaches the synchronized state, yet experience a period of frequency and phase fluctuations which can be divided into two stages. The first stage time is influenced by the frequency detuning between the perturbation force and the oscillator. The second stage time is determined by the configuration of the potential well which is influenced by the nonlinearity terms. We found that the dynamic behavior of the frequency and phase can be regulated by the energy potential well of the nonlinear feedback system. By reconfigure the potential well pattern, we achieve 5 times suppression of the synchronization process, which have promising beneficial effects for the aspects of sensor application. Similar phenomena can be found in human body dynamics, which means that the observed mechanism can give some suggestions to study life science.
High flow nasal oxygen therapy compared with conventional oxygen therapy in hospitalised patients with respiratory illness: a systematic review and meta-analysis
Authors: Seow Daniel , Khor Yet H. , Khung Su-Wei , Smallwood David M , Ng Yvonne , Smallwood Natasha E
Published: January 2023

Background
This systematic review aims to summarise the evidence regarding any benefits of high flow nasal oxygen (HFNO) therapy compared to conventional oxygen therapy (COT) in hospitalised patients with acute or chronic respiratory illnesses.
Methods
A comprehensive search was performed across three databases for studies that reported any of: escalation to invasive mechanical ventilation (IMV), mortality, length of stay, carbon dioxide levels, disability, or admission rates.
Results
In patients with acute respiratory illnesses, pooled RCT data revealed no significant differences between HFNO and COT in overall need for IMV (RR = 0.82, 95% CI = 0.65–1.05; p = 0.11; n = 15 RCTs) or in-hospital mortality (RR = 1.00, 95% CI 0.85–1.17; p = 1.00; n = 5). Similarly, for patients with chronic respiratory illnesses, RCT data revealed no significant difference in overall need for IMV (RR = 0.86, 95% CI = 0.33–2.23; p = 0.76; n = 4) or in-hospital mortality (RR = 0.40, 95% CI = 0.04–4.10; p = 0.44; n = 1) for HFNO compared to COT. Patients with COVID-19 receiving HFNO had a significantly reduced need for IMV (RR = 0.72, 95% CI = 0.63–0.82; p < 0.001), short-term mortality (RR = 0.62, 95% CI = 0.48–0.79; p < 0.001), and long-term mortality (RR = 0.67, 95% CI = 0.48–0.92; p = 0.01).
Conclusion
HFNO did not significantly reduce the need for IMV escalation or in-hospital mortality in patients with acute or chronic respiratory illnesses, except for patients with COVID-19.
Scanless two-photon voltage imaging
Authors: Sims Ruth , Bendifallah Imane , Grimm Christiane , Lafirdeen Aysha , Lu Xiaoyu , St-Pierre François , Papagiakoumou Eirini , Emiliani Valentina
Published: January 2023

Parallel light-sculpting methods have been used to perform scanless two-photon photostimulation of multiple neurons simultaneously during all-optical neurophysiology experiments. We demonstrate that scanless two-photon excitation also enables high-resolution, high-contrast, voltage imaging by efficiently exciting fluorescence in a large fraction of the cellular soma. We present a thorough characterisation of scanless two-photon voltage imaging using existing parallel approaches and lasers with different repetition rates. We demonstrate voltage recordings of high frequency spike trains and sub-threshold depolarizations in intact brain tissue from neurons expressing the soma-targeted genetically encoded voltage indicator JEDI-2P-kv. Using a low repetition-rate laser, we perform recordings from up to ten neurons simultaneously. Finally, by co-expressing JEDI-2P-kv and the channelrhodopsin ChroME-ST in neurons of hippocampal organotypic slices, we perform single-beam, simultaneous, two-photon voltage imaging and photostimulation. This enables in-situ validation of the precise number and timing of light evoked action potentials and will pave the way for rapid and scalable identification of functional brain connections in intact neural circuits.
An assessment of the strategies for the energy-critical elements necessary for the development of sustainable energy sources
Authors: Krishna RAM , Dhass Avithi Desappan , Arya Abhishek , Prasad Ranjit , Colak Ilhami
Published: January 2023

There have been several strategies developed in order to increase the diversified supply of energy so that it can meet all of the demands for energy in the future. As a result, to ensure a healthy and sustainable energy future, it is imperative to warrant reliable and diverse energy supply sources if the “green energy economy” is to be realized. The purpose of developing and deploying clean energy technologies is to improve our overall energy security, reduce carbon footprint, and ensure that the generation of energy is secure and reliable in the future, making sure that we are in a position to spur economic growth in the future. In this paper, advancements in alternative sources of energy sustainability and strategies will be examined, so as to ensure there will be enough fuel to supply all of the future demands for energy. Several emerging clean energy technologies rely heavily on the availability of materials that exhibit unique properties that are necessary for their development. This paper examines the role that materials, such as rare earth metals and other critical materials, play in securing a clean energy economy and the development of clean energy economies in general. In order for the development of these technologies to be successful and sustainable, a number of these energy-critical materials are at risk of becoming unavailable. This is due to their limited availability, disruptions in supply, and the lack of suitable resources for their development. An action plan focusing on producing energy-critical materials in energy-efficient ways is discussed as part of an initiative to advance the development of clean and sustainable energy.
Post-depositional Hg transformation processes in an open boreal peatland constrained by Hg stable isotopes
Authors: Li Chuxian , Jiskra Martin , Nilsson Mats B. , Osterwalder Stefan , Zhu Wei , Mauquoy Dmitri , Skyllberg Ulf , Enrico Maxime , Peng Haijun , Song Yu , Björn Erik , Bishop Kevin
Published: January 2023

Peatland vegetation constantly takes up mercury (Hg) from the atmosphere, typically contributing to net production and export of neurotoxic Methyl-Hg to downstream ecosystems. Chemical reduction processes can slow down Methyl-Hg production by releasing Hg from peat back to the atmosphere. The extent of these processes remain, however, unclear. Here we present results from a comprehensive study covering concentrations and isotopic signatures of Hg in an open boreal peatland system to identify post-depositional Hg transformation processes. Isotope mass balances suggest photoreduction of HgII is the predominant process by which 30% of annually deposited Hg is emitted back to the atmosphere. Isotopic analyses indicate that dark abiotic oxidation decreases peat soil gaseous Hg0 concentrations above the water table, and that supersaturated gaseous Hg below the water table was likely created more by photoreduction of rainfall rather than release from peat soil. These findings constrain the possibilities for mobilizing previously deposited Hg. Identification and quantification of these processes further advance our understanding of the fate of Hg in peatlands and their export of Methyl-Hg to downstream ecosystems.
Intraspecific inflorescence and palynological variations in the morphotypes of Amorphophallus paeoniifolius
Authors: Anil Shirly Raichal , Devi A. Asha , Asha K.I. , Beevy S. Suhara , Siril Elengikkal Avarachan
Published: January 2023

The genus Amorphophallus Blume ex Decne. is a vast and widespread group of aroids belonging to Araceae which is taxonomically and botanically distinct due to the frequency of emergence of inflorescences and their relatively short active period of existence. Amorphophallus paeoniifolius var. campanulatus or the elephant foot yam is an important tuber crop due to its high productivity and popularity as a vegetable in various delicious cuisines and medicinal properties. Wild congenerics of the cultivated A. paeoniifolius known as A. paeoniifolius Nicolson var. paeoniifolius (Decne.) Sivad. possess powerful therapeutic action against piles and gastro-intestinal disorders. The wide visible morphological variation observed in wild A. paeoniifolius morphotypes (morphological variants) available in the Western Ghats especially in the vegetative as well as inflorescence characters led to the present investigation to analyze and appraise the inflorescence diversity in comparison with other aspects, among the wild relatives of Amorphophallus paeoniifolius. Variation in the surface pattern of petiole and spathe is the main difference found within the species. The shape of appendix, the colour and pattern of spathe, scale leaves (bract) subtending the spathe, the male zone, female zone, the pollen morphology as assessed by SEM and pollen fertility showed distinct variation within the species revealing six distinct morphotypes. The mitotic chromosome studies indicated structural variation which was reflected in the karyomorphology. The ISSR markers, inflorescence /floral markers and vegetative morphological descriptors also indicated clear distinction between the morphotypes in addition to the variation seen in pollen morphology
Uplink Interference Mitigation in HetNets with Q-Learning Algorithm
Authors: Abbasi-Moghadam Dariush , Etminan Khatereh , Kalantarinejad Nazanin
Published: January 2023

Interference cancellation is one of the important issues in Heterogeneous networks (HetNets), due to the density of the network. In this paper, we investigate the problem of interference cancellation and resource allocation with the Q-learning approach. We consider the Inter-interference and Intra-interference between the femtocell and macro cells in the uplink scenario. With the aim of maximizing the QoS of the macro user equipment (MUE) and minimizing the interference of the MUE, a new reward function was proposed. The simulation results show the improvement of the proposed algorithm in two strong interference and increasing distance scenarios.
A Radioactive and Fluorescent Dual Modality Cysteine Cathepsin-B Activity-Based Probe for Cancer Theranostic
Authors: Zhou Lianbo , He Feng , Xiang Xing , Dong Chuning , Xiang Tian , Li Xian , Li Hong , Bu HongLi , Wang Yunhua , Ma Xiaowei
Published: January 2023

Purpose: Cysteine cathepsin B (CTS-B) is a crucial enzyme that is overexpressed in numerous malignancies and contributes to the invasion and metastasis of cancer. Therefore, this study set out to develop and evaluate an activity-based multi-modality theranostic agent targeting CTS-B for cancer imaging and therapy.
Methods: A CTS-B activity-based probe, BMX2, was synthesized and labeled efficiently with 68Ga and 90Y to produce 68Ga-BMX2 for multi-modality imaging and 90Y-BMX2 for radiation therapy. The affinity and specificity of the BMX2 binding with the CTS-B enzyme were determined by fluorescent western blot using recombined active human CTS-B enzyme (rh-CTS-B) and four cancer cell lines including HeLa, HepG2, MCF7, and U87MG with CA074 as CTS-B inhibitor for control. Confocal laser scanning microscope imaging and cell uptake measurement was also performed. Then in vivo PET imaging and fluorescence imaging were acquired on HeLa xenografts. Finally, the therapeutic effect of 90Y-BMX2 was tested.
Results: BMX2 could be specifically activated by rh-CTS-B and stably bound to the enzyme. The binding of BMX2 with CTS-B has a time-dependent and enzyme concentration-dependent manner. Although CTS-B expression varied between cell lines, all showed significant uptake of BMX2 and 68Ga-BMX2. In vivo optical and PET imaging showed high tumor uptake of BMX2 and 68Ga-BMX2 and accumulated for more than 24 hours. The 90Y-BMX2 could significantly inhibit HeLa tumor growth.
Conclusion: The development of 68Ga/90Y-BMX2, a radioactive and fluorescent dual modality theranostic agent, demonstrated an effective theranostic approach for PET diagnostic imaging, fluorescence imaging, and radionuclide therapy of cancers, which may have a potential for clinical translation for cancer theranostic in the future.
Machine learning based routing protocol (MLBRP) for Mobile Internet of Things networks
Authors: Larouci Nour El Houda , Sahraoui Somia , Djeffal Abdelhamid
Published: January 2023

Massive volumes of data generated by large numbers of connected Internet of Things (IoT) devices impact both IoT service and network performance. Packet routing is an ever-important networking feature that enables the transmission of data packets across interconnected IoT networks. Usually, classical proactive and reactive routing protocols use the information of their neighbours to build a global view of the network by the mean of control messages and then calculate a path to the destination. After a packet has been delivered, history is discarded, and only actual information is used to determine new paths. In the present research work, we propose applying a Machine Learning (ML) approach to take advantage of previously successfully taken routing decisions and build new decision models that nodes can use to make intelligent routing decisions. In our proposal, we integrate three machine learning techniques: Decision Trees(DT), Support Vector Machines (SVM), and Artificial Neural Networks (ANN) into the well-known Ad hoc On-demand Distance Vector (AODV) routing protocol and evaluate the efficiency of solution variants for packets routing in IoT-connected smart city scenario. The assessment results show that the proposed ML-based routing solutions outperform the AODV protocol and decrease the use of control messages to more than 50% of the overall communication overhead. Therefore, network performances are more optimized, and network lifetime is also increased.
Resistance mechanism to Notch inhibition and combination therapy in human T cell acute lymphoblastic leukemia
Authors: Radtke Freddy , Cao Linlin , Buendía Gustavo Ruiz , Fournier Nadine , Liu Yuanlong , Armand Florence , Hamelin Romain , Pavlou Maria
Published: January 2023

Gain-of-function mutations in NOTCH1 are among the most frequent genetic alterations in T cell acute lymphoblastic leukemia (T-ALL), making the Notch signaling pathway a promising therapeutic target for personalized medicine. Yet, a major limitation for long-term success of targeted therapy is relapse due to tumor heterogeneity or acquired resistance. Thus, we performed a genome-wide CRISPR-Cas9 screen to identify prospective resistance mechanisms to pharmacological NOTCH inhibitors and novel targeted combination therapies to efficiently combat T-ALL. Mutational loss of Phosphoinositide-3-Kinase regulatory subunit 1 (PIK3R1) causes resistance to Notch inhibition. PIK3R1 deficiency leads to increased PI3K/AKT signaling which regulates the cell cycle and spliceosome machinery, both at the transcriptional and post-translational level. Moreover, several therapeutic combinations have been identified, where simultaneous targeting of the cyclin-dependent kinases 4 and 6 (CDK4/6) and NOTCH proved to be the most efficacious in T-ALL xenotransplantation models.
Analysis of genetic diversity and population structure in Cambodian melon landraces using molecular markers
Authors: Naznin Pervin Mst , Imoh Odirichi Nnennaya , Tanaka Katsunori , Sreyn Ouch , Shigita Gentaro , Sophea Yon , Sophany Sakhan , Makara Ouk , Tomooka Norihiko , Monden Yuki , Nishida Hidetaka , Kato Kenji
Published: January 2023

Genetic diversity of Cambodian melon was evaluated by the analysis of 12 RAPD and seven SSR markers using 62 accessions of melon landraces, and compared with 231 accessions from other areas for genetic characterization of Cambodian melon. Among 62 accessions, 56 accessions were morphologically classified as small-seed type whose seed length was shorter than 9mm as like groups Conomon and Makuwa. Gene diversity of Cambodian melon was 0.228 which was equivalent to those of groups Conomon and Makuwa and smaller than those of Vietnamese and Central Asian landraces. Phylogenetic tree constructed from genetic distance matrix classified 293 accessions into three major clusters. Small-seed type accessions from east and southeast Asia formed clusters I and II, which were distantly related with cluster III consisted of large-seed type melon from other areas. All of Cambodian melon belonged to cluster I except three accessions, along with those from Thailand, Myanmar, Yunnan (China) and “Dua thom” from northwestern part of Vietnam, indicating genetic similarity in these areas. In addition, Cambodian melon was not differentiated among geographical populations. Conomon and Makuwa were classified into cluster II, together with melon groups from plain areas of Vietnam. The presence of two groups of melon in southeast Asia was also indicated by population structure and PCO analysis. These results indicated close genetic relationship between Cambodia and the neighboring countries, and suggested that Cambodian melon is not directly related with the establishment of Conomon and Makuwa.
Age-related elevation of O-GlcNAc causes meiotic arrest and subfertility in male mice
Authors: Yao Bing , Qian Zhang , Li Chuwei , Zhao Shanmeizi , Zhang Hong , Ma Rujun , Ge Xie , Jing Jun , Chen Li , Ma Jinzhao , Zheng Lu , Zhang Kemei , He Zhaowanyue , Xue Mengqi , Lin Ying , Jueraitetibaike Kadiliya , Feng Yuming , Cao Chun , Tang Ting , Sun Shanshan , Teng Hui , Zhao Wei
Published: January 2023

In recent years, the postponement of childbearing has become a critical social issue. Male fertility is negatively associated with age because of testis aging. Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging.
A High-throughput screening system for SARS-CoV-2 entry inhibition, syncytia formation and cell toxicity
Authors: Jancy Shine Varghese , Lupitha Santhik Subhasingh , Chandrasekharan Aneesh , Varadarajan Shankara Narayanan , Nelson-Sathi Shijulal , Prasad Roshny , Jones Sara , E Sreekumar , T.R. Santhoshkumar
Published: January 2023

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry to host cell is mediated through the binding of the SARS-CoV-2 Spike protein via receptor binding domain (RBD) to human angiotensin-converting enzyme 2 (hACE2). Identifying compounds inhibiting Spike-ACE2 binding would be a promising, safe antiviral approach against COVID-19.
Methods: In the present study, we have used BSL-2 compatible replication-competent vesicular stomatitis virus (VSV) replaced glycoprotein with spike protein of SARS-CoV-2 expressing eGFP reporter system (VSV-eGFP-SARS-CoV2) in a permissive cells harboring cytotoxicity marker. The high-throughput compatible SARS-CoV-2 permissive reporter system that encompasses cells stably expressing hACE2 tagged cerulean and nuclear H2B tagged with mCherry, as a marker of nuclear condensation that also enabled imaging of fused cells among infected EGFP positive cells and could give real-time information of syncytia formation.
Results: A limited high-throughput screening identified six natural products with marked VSV-eGFP-SARS-CoV2 inhibition at non cytotoxic dose. Molecular simulation studies with positive hits in complex with wild-type spike reaffirm their potential to impede viral entry. Real-time syncytia formation assay of the molecules revealed inhibition of syncytia with Didemnin B, and delayed inhibition with other natural products such as Scillaren A, Proscillaridin, Acetoxycycloheximide indicating that the assay is a reliable platform for any image based drug screening.
Conclusion: BSL-2 compatible assay system equivalent to the infectious SARS-CoV-2 is a promising tool for high-throughput screening of large compound libraries for viral entry inhibitors against SARS-CoV-2 along with toxicity and effect on syncytia. Studies using clinical isolates of SARS-CoV-2 is warranted to confirm the antiviral potency of the leads and the utility of the screening system.
Tumor-nonspecific vaccines improve the efficacy of CD3 bispecific antibody therapy in solid tumors
Authors: Middelburg Jim , Sluijter Marjolein , Schaap Gaby , Göynük Büşra , Lloyd Katy , Ovcinnikovs Vitalijs , Zom Gijs , Marijnissen Renoud , Sandker Gerwin , Heskamp Sandra , Burg Sjoerd van den , Arakelian Tsolere , Ossendorp Ferry , Arens Ramon , Schuurman Janine , Kemper Kristel , Hall Thorbald van
Published: January 2023

CD3 bispecific antibody (CD3 bsAb) therapy is clinically approved for refractory hematological malignancies, but responses in solid tumors have been limited so far. One of the main hurdles in solid tumors is the lack of sufficient T-cell infiltrate. Here, we show that pre-treatment vaccinations, even when they comprised tumor-unrelated antigens, induced CXCR3-mediated T-cell influx in immunologically ‘cold’ mouse tumor models. In the absence of CD3 bsAb, the infiltrate was mainly confined to the tumor invasive margin, however subsequent CD3 bsAb administration induced profound infiltration of activated effector CD8 T cells into the tumor cell nests. This combination therapy installed a broadly inflamed Th1-type tumor microenvironment, resulting in effective tumor eradication. Interestingly, multiple vaccination strategies, including synthetic long peptides, viruses and COVID-19 mRNA, empowered CD3 bsAb therapy. Our results imply that eliciting tumor infiltration with vaccine-induced tumor non-specific T cells can greatly improve the efficacy of CD3 bsAbs in solid tumors.
Estimating prevalence of bereavement, its contribution to risk for binge drinking, and other high-risk health states in a state population survey, 2019 Georgia Behavioral Risk Factor Surveillance Survey
Authors: Miles Toni , Li Changle , Khan M Mahmud , Bayakly Rana , Carr Deborah
Published: January 2023

Background: This report examines the cross-sectional association between new bereavement and binge drinking. Bingeing is defined as 4 or more drinks (women) or 5 or more drinks (men) in a 2-to-4-hour setting. In the 2019 Georgia Behavioral Risk Factor Surveillance Survey (BRFSS), bereavement is a defined as a ‘Yes’ answer to ‘Have you experienced the death of a family member or close friend in the years 2018 or 2019?’.
Methods: Georgia BRFSS is a complex sampling survey administered annually. It is designed to represent the 8.1 million persons in the U.S. state of Georgia aged 18 years and older. Alcohol consumption is routinely measured in the common core. In 2019, the state added a new item probing for bereavement in the prior 24 months predating the pandemic of COVID-19. Imputation and weighting techniques were applied to yield population prevalence rates of new bereavement, bingeing, and their co-occurrence with other high-risk health states. Models, adjusted for age, gender, and race were used to estimate the risk for other unhealthy behaviors posed by the co-occurrence of bereavement and bingeing.
Results: In Georgia, bereavement is common (45.8 %), and alcohol consumption is common (48.8 %). Bereavement and alcohol use co-occurred among 1,796,817 persons (45 % of all drinkers). The subset of co-occurring bereavement and binging totaled 608,282 persons. Within this group, the highest rates of bereavement were associated with death of a friend / neighbor (30.7%) or 3 plus deaths (31.8%).
Conclusions: While bingeing is a known risk to public health, its co-occurrence with new bereavement is a new observation. Public health surveillance systems need to monitor this co-occurrence to protect both individual and societal health.
Modeling of the effect of subperiosteal hydrostatic pressure conductivity between joints on decreasing contact loads on cartilages. Floating skeleton theory
Authors: Pitkin Mark R.
Published: January 2023

Chronic overloading of cartilages may lead to their irreversible destruction, as seen in people with osteoarthritis. We hypothesize that overloading begins and progressing when one or more joints become isolated from the newly discovered physiological system - Floating Skeleton (FS), devoted to keeping the loads in a safe range. To demonstrate in a model experiment how subperiosteal hydrostatic pressure conductivity between joints decreases contact loads on cartilages we constructed a physical model from a commercial Ziploc bag, which walls have been glued together in its center with a small caramel plug. After pouring water in the bag, we put a standardized weight on the upper wall of the bag over the caramel plug and recorded the load transmitted to the measuring plate directly under the plug. Then, the caramel plug was dissolved so that an unobstructed water layer between the bag’s walls was restored. The same weight was placed at the same spot and the load on the measuring plate was recorded. Restoration of the water layer between the bag’s walls caused a reduction of the load. The experiments conclusively demonstrated that contact pressures can be redistributed when the conditions of the Pascal Law are met.
Identification of psycho-socio-judicial trajectories and factors associated with PTSD after recent sexual assault: the IADViSe study protocol for a multi-centric prospective study using mixed methods and artificial intelligence
Authors: Fedele Emma , Trousset Victor , Schalk Thibault , Oliero Juliette , Fovet Thomas , Lefevre Thomas
Published: January 2023

Background Sexual assault (SA) has numerous negative outcomes on physical, sexual and mental health, social life, financial stability and overall quality of life. It is known as one of the most traumatogenic event. However, not all people who experienced SA will develop negative functional outcomes. Multiple risk and protection factors can influence their psycho-socio-judicial trajectories. The way by which these factors impact trauma adaptation are not always clear. Guided by an ecological framework, this project aims to (1) describe psycho-socio-judicial one-year trajectories of people recently exposed to SA, to (2) identify predictive factors for the development of posttraumatic stress disorder (PTSD) at first forensic examination using artificial intelligence and to (3) explore the notions of “victim” and “trauma” and the needs and experiences of people who have been sexually assaulted. Methods and design This longitudinal multi-centric cohort study will use a mixed-method approach. Quantitative cohort data will be collected based on questionnaires repeated in time, starting from first forensic examination and covering up to a year after the SA, measuring factors associated with PTSD, mental, physical, social and overall functional outcomes, and psycho-socio-judicial trajectories. Qualitative data will be based on semi-structured interviews with members of the cohort, people who experienced SA but not included in the cohort, and actors professionally involved in their psycho-socio-judicial care. Bivariate and multivariate analyses will be performed to study the associations between each variable and mental, physical, social and judicial outcomes. Predictive analyses will be conducted on multiple prediction algorithms to predict PTSD. Qualitative data will be integrated to the quantitative data to identify psycho-socio-judicial trajectories of participants and data on the representations of the place and usefulness of the notions of “trauma” and “victims” will be used independently. Discussion This project will collect numerous data never before collected over such long periods, which will lead to unprecedented results on psycho-socio-judicial trajectories of people who experienced SA. By being based on the entire psycho-socio-judicial chain and on the perspective of people who experienced SA, this work will allow to make innovative recommendations to improve their care at all levels, from the initial forensic examination.
Mortality Related Factors in Penetrating Abdominal Trauma
Authors: Bernal Andrés Felipe , Latiff Mario Alberto , Núñez-Rocha Ricardo E. , Rodríguez Lina M , Sierra Andres Mauricio Garcia , Rey Carlos , Tabares Raquel , Alvarado Kelly , Espitia David , Conde Danny , Hernández Juan David , Girón Felipe
Published: January 2023

Background: Penetrating abdominal trauma is a frequent cause of death in Latinamerica with high rates of morbidity and mortality. A wide variety of therapeutic appraches have been proposed for the manegement of this pathology. In this study, we aimed to analyze the factors related to mortality and to describe outcomes of patients in penetrating abdominal trauma.
Methods: Retrospective review of a prospectively collected database was performed. All patients with penetrating abdominal, or thoracoabdominal injury that required urgent laparotomy or laparoscopic exploration between 2018-2020 in our institution were included.
Results: A total of 231 patients were included. Male patients were 92.21% and the median age was 28 IQR (22-37). 56.2% patients were ASA I, 19.9% ASA II, 4.7% ASA III, 7.3% ASA IV and 11.6% unknown. 77.5% patients had sstab wounds as penetrating abdmonal trauma etiology and 22.1% by gunshots. 76.2% of the wounds were made in the thoracoabdominal area, 73.8% were abdominal injuries and 24.2% were thoracic. 77.9% of patients presented a PATI score under 25 points. Comorbidities, gunshot wounds, ASA, need of blood product transfusion, number of pRBC needed, surgical approach and organ injury had a statistically significant association (p<0.05) with total mortality and mortalifty after 48 hours. There was also a statistically significant association between comorbidities (OR 407.405 [1.4-118534.05 95% IC]), ASA III (OR 0.004 [0-0.644 95% IC]), and blood product transfusion (OR 0 [0-0.877 95% IC]) with overall mortality.
Conclusion: PATI scale appear to be a feasible tool to predict worst outcomes in abdominal penetrating trauma patients. Residents as first surgeons showed no evidence of a higher complications rate.
Industrial Wastewater Irrigation Increased Higher Heavy Metals uptake and Expansins, Metacaspases, Cystatin Genes Expression in Parthenium and Maize
Authors: Penzy Kinza , Muhammad Said , Shahzad Muhammad , Hussain Imran , Khan Sabaz Ali , Abbasi Arshad Mehmood , Khan Imtiaz , Ahmad Rafiq
Published: January 2023

Industrial wastewater irrigation of agriculture crops could cause a lot of environmental and health problems in developing countries due to heavy metals deposition in agriculture soils as well as edible plants consumption by human beings. Therefore, this study was conducted to find out heavy metals’ concentration in industrial wastewater and soil irrigated with that wastewater. In addition, the impact of industrial wastewater irrigation on Parthenium hysterophorus and Zea mays genes involved in growth improvement and inhibition of selected plants. For this purpose, plant samples from agriculture fields irrigated with wastewater from Hattar Industrial Estate (HIE) of Haripur, Pakistan and control plants from non-contaminated soil irrigated with tape water were collected after fifteen and forty-five days of germination. Heavy metals concentration in the collected plant samples, wastewater and soil were determined and results revealed that the study area was predominantly contaminated with Cr, Pb, Ni, Cu, Co, Zn and Cd concentrations of 38.98, 21.14, 46.01, 155.73, 12.50, 68.50 and Cd 7.01 mg/kg, respectively. The concentrations of these heavy metal have surpassed permissible limit of these metals in normal agriculture soil. Expansins and cystatin (plant growth enhancers), metacaspases (plant growth inhibitor) genes expression were studied through reverse transcription polymerase chain reaction and results showed that the expression of these genes was higher in samples collected from wastewater-irrigated soils as compared to control. More expression of these genes was observed in 45 days old samples as compared to 15 days old samples and control. Taken together, this study suggests the use of Parthenium and maize for phytoremediation, however, they should not be used for eating purposes if irrigated with industrial wastewater.
Mitochondrial Aconitase enzymatic activity: a potential long survival biomarker in the blood of ALS patients
Authors: González-Mingot Cristina , Miana Francisco Javier , Iñarrea Pedro , Iñíguez Cristina , Capablo JoseLuis , Osta Rosario , Gil-Sánchez Anna , Peralta Silvia , Brieva Luis , Larrode Pilar
Published: January 2023

Background: Amyotrophic Lateral Sclerosis (ALS) is a multisystemic, progressive, neurodegenerative disorder. Despite it being generally fatal within a period of 2–4 years, it is highly heterogeneous; as a result, survival periods may vary greatly among individual patients. In the absence of a single reliable test for ALS, Biomarkers can serve as tools for diagnosis, prognosis, indicators of therapeutic response, and future therapeutics. Free radical-dependent mitochondrial damage is believed to play a crucial role in neurodegeneration in ALS. Mitochondrial Aconitase, which is also known as Aconitase 2 (Aco2), is a key Krebs cycle enzyme and is involved in the regulation of cellular metabolism and iron homeostasis. Aco2 is very sensitive to oxidative inactivation and can aggregate and accumulate in the mitochondrial matrix, causing mitochondrial dysfunction. A loss of Aco2 activity may therefore reflect increased levels of mitochondrial dysfunction due to oxidative damage and could be relevant to ALS pathogenesis.
The aim of our study was to confirm changes in Mitochondrial Aconitase activity in peripheral blood and to determine whether such changes are dependent on, or independent of, the patient's condition and to explore the feasibility of using them as valid biomarkers for quantifying disease progression and as an individual prognosispredictor in ALS.
Methods: We measured Aco2 enzymatic activity in platelets of blood samples taken from 22 controls and 26 ALS patients at different stages of disease development. We then correlated antioxidant activity with clinical and prognostic variables.
Results: Aco2 activity was significantly lower in the 26 ALS patients than in the 22 controls (p<0.05). Patients with higher levels of Aco2 activity survived longer than those with lower levels (p<0.05). Aco2 activity was also higher in patients with earlier onsets (p< 0.05) and in those with predominantly upper motor neuron signs.
Conclusions: Aco2 activity is an independent factor that can be used in the long-survival prognosis of ALS. Our findings suggest that blood Aco2 is a leading candidate for use as a biomarker for improving prognosis. It could facilitate participant stratification in future ALS therapeutic trials and offer additional potential for therapeutic targeting.
Efficacy of adipose-derived stem cells combined with different scaffolds to repair bone defects: a systematic review and Meta-analysis
Authors: XIONG YB , LIU JH , HE YH , LI CL
Published: January 2023

At the present stage, the most traditional techniques for the treatment of bone defects often fail to achieve the desired results. The tissue engineering technology about bone regeneration emerged as a new method for treating bone defects. Cells and scaffolds are the two most important key factors in tissue engineering, and there are many types of scaffolds are already in use in experiments. And there are so many studies are now on different Cellular scaffolds filled with ADSCs (adipose-derived stem cells). But these researches are still in the animal experimental stage. This study informed the clinical application of ADSCs through an evidence-based medicine analysis to evaluate the efficacy of ADSCs in repairing the bone defect. We systematically searched databases, collected relevant studies, and screened them, then analyzed the data using specialized tool and rated the credibility of the results at the end. The final results concluded that the efficiency of treatment of ADSCs combined with scaffold treatment group was superior to the control group. Quality of evidence (GRADE): high. The combination of ADSCs with cellular scaffolds may be effective in promoting repair of bone defects. However, additional, more demanding experiments are still needed to test the effect of ADSCs on bone regeneration.
Using DNA barcoding to relate cystacanths and adults of Corynosoma australe (Acanthocephala: Polymorphidae) of the Southeastern Pacific Ocean (Off Peru Coast)
Authors: Mondragón-Martínez Aarón , Dávila-Rios Martín , Martínez-Rojas Rosa , Cruz-Neyra Lidia , Gorbeña Juan C. Ramos , Dávila-Robles Miguel , Garcia-Candela Enrique , De-Los-Santos Estrellita Rojas , Delgado-Escalante Abraham , Sanchez-Venegas J.R , Pulido-Murillo Eduardo A.
Published: January 2023

The objective of this study is to use DNA barcoding to relate cystacanths and adults belonging to the acanthocephalans genus Corynosoma found in the southeastern Pacific Ocean off the coast of Peru. For this, we sampled three species of commercial fish (Paralichthys adspersus, Paralabrax humeralis and Cheilodactylus variegatus) and two South American sea lions Otaria byronia stranded on the beaches of the city of Huacho and Barranca, department of Lima. A total of 509 larvae were found in the body cavity of 95 fish (total prevalence 54.28%, total mean intensity 8.64), moreover, a total of 127 adults were found in the large intestine of two South American sea lion (P = 100%, MI = 63.5). We isolated 203 larvae of P. humeralis (P = 65.71%; MI = 8.83; MA = 5.8), 235 (P = 54.29%; MI = 12.37; MA = 6.71) of C. variegatus and 71 (P = 42.86%; MI = 4.73; MA = 2.03) of P. adspersus. All adult and larval specimens were morphologically identified as Corynosoma sp. We performed phylogenetic analysis and generated cytochrome c oxidase subunit 1 (cox1) gene sequences that were compared with sequences available from GenBank. Likewise, using maximum likelihood (ML) and Bayesian inference (BI) revealed that the 16 new sequences (four adults and twelve larvae) were grouped into a clade formed by Corynosoma australe. Therefore, our results contribute to broaden the range of paratenic hosts as well as to record the presence of C. australe in the definitive host. In addition, it is the first analysis that confirms the presence of C. australe using DNA barcoding, allowing its geographical distribution to be extended to the Southeast Pacific Ocean off the coast of Peru.
Restored UBE2C expression in islets promotes β-cell regeneration in mice by ubiquitinating PER1
Authors: Jiang Hemin , Zheng Shuai , Qian Yu , Zhou Yuncai , Dai Hao , Liang Yucheng , He Yunqiang , Gao Rui , Lv Hui , Zhang Jie , Xia Zhiqing , Bian Wenxuan , Yang Tao , Fu Qi
Published: January 2023

Background
The limited proliferation capacity of β-cells contributes to insulin insufficiency, which promotes the onset of diabetes. β-cells secrete multiple beneficial substances, except for insulin; therefore, the regeneration mechanism of β-cells requires further study. Previously, ubiquitin-binding enzyme 2C (UBE2C) was reported to be downstream of the key β-cell transcription factor NKX6.1, but the specific function and mechanism of UBE2C in pancreatic islets remain unknown.
Methods
We performed islet perfusion, immunofluorescence staining, and transmission electron microscopy (TEM) to examine the role of UBE2C in mice with a Cre-loxP-constructed β-cell-specific knockout (βUbe2cKO) or overexpression through lentivirus infusion within the pancreatic ducts. Single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq, tandem mass tag (TMT) quantification proteomics, immunoprecipitation, and immunoblotting were conducted to explore the mechanisms by which UBE2C regulates β-cell proliferation.
Results
We discovered that ubiquitin-conjugating enzyme E2C (UBE2C) was highly expressed in a β-cell subgroup, which exhibited active proliferation capacity. We confirmed that UBE2C promotes β-cell compensatory proliferation by activating cell cycle renewal during a high-fat diet (HFD) and weaning. Consequently, β-cell-specific Ube2c knockout (βUbe2cKO) mice developed typical type 2 diabetes owing to β-cell loss caused by insulin insufficiency. Mechanistically, UBE2C combines with CUL1 to regulate PER1 degradation through ubiquitination. Notably, restored Ube2c expression in islets activated β-cell regeneration in streptozotocin (STZ)-induced diabetic mice, and alleviated diabetic hyperglycaemia and glucose intolerance.
Conclusion
This study indicates that UBE2C positively regulates β-cell proliferation by promoting ubiquitination and degradation of the biological clock suppressor PER1. The UBE2C-mediated beneficial effects on β-cells suggest a promising application in the treatment of diabetic patients with β-cell deficiency.