bluuebunny/crossref_metadata_2025_split huggingface dataset:
Honey bees can store and retrieve independent memory traces after complex experiences that combine appetitive and aversive associations
Authors: Klappenbach Martín , Lara Agustín E. , Locatelli Fernando F. 
Published: April 2022

ABSTRACT
Real-world experiences often mix appetitive and aversive events. Understanding the ability of animals to extract, store and use this information is an important issue in neurobiology. We used honey bees as model organism to study learning and memory after a differential conditioning paradigm that combines appetitive and aversive training trials. First, we used an aversive conditioning paradigm that constitutes a clear opposite of the well-known appetitive olfactory conditioning of the proboscis extension response. A neutral odour is presented paired with the bitter substance quinine. Aversive memory is evidenced later as an odour-specific impairment in appetitive conditioning. Then, we tested the effect of mixing appetitive and aversive conditioning trials distributed along the same training session. Differential conditioning protocols like this were used previously to study the ability to discriminate odours; however, they were not focused on whether appetitive and aversive memories are formed. We found that after differential conditioning, honey bees establish independent appetitive and aversive memories that do not interfere with each other during acquisition or storage. Finally, we moved the question forward to retrieval and memory expression to evaluate what happens when appetitive and the aversive learned odours are mixed during a test. Interestingly, opposite memories compete in such a way that they do not cancel each other out. Honey bees showed the ability to switch from expressing appetitive to aversive memory depending on their satiation level.
Moral injury and psychological resilience among healthcare professionals amid COVID-19 pandemic
Authors: Akhtar Mubeen , Faize Fayyaz Ahmad , Malik Ramla Zaid , Tabusam Asifa 
Published: April 2022

Objectives: The present research studied moral injury and psychological resilience in healthcare professionals amid COVID-19 pandemic. Relationship between moral injury and resilience was explored in addition to finding the difference in study variables based on socio-demographics factors.
Methods: This cross-sectional research was carried out from August 2020 to January 2021. A sample of 108 healthcare professionals including doctors, nurses, and paramedical staff was collected through purposive sampling technique. Data was gathered through face-to-face survey method and online forum using psychometrically sound tools.
Results: Findings revealed that more than two third of the sample (69.44%) has high level of moral injury which is clinically significant while only 30.56% fall within normal range. Moral injury has significant positive correlation with number of work hours (p < .05) whereas negative correlation with resilience (p < .01) and years of experience (p < .05). Women and health care professionals belonging to psychiatry department have reported to experience significantly high level of moral injury (p < .01).
Conclusion: The findings of the study are helpful for stakeholders of health care system to better understand and prepare for the situations that brings moral injury and challenge psychological resilience particularly in times of pandemic, humanitarian crisis, or natural disasters.
doi: https://doi.org/10.12669/pjms.38.5.5122
How to cite this:Akhtar M, Faize FA, Malik RZ, Tabusam A. Moral injury and psychological resilience among healthcare professionals amid COVID-19 pandemic. Pak J Med Sci. 2022;38(5):---------. doi: https://doi.org/10.12669/pjms.38.5.5122
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
In vitro and in vivo study: Ethanolic extract leaves of Azadirachta indica Juss. variant of Indonesia and Philippines suppresses tumor growth of hepatocellular carcinoma by inhibiting IL-6/STAT3 signaling
Authors: Raissa Ricadonna , Riawan Wibi , Safitri Anna , Masruri Masruri , Beltran Ma Asuncion Guiang , Aulanniam Aulanniam 
Published: April 2022

Background: Azadirachta indica Juss. has been shown to suppress cancer progression through a variety of mechanisms. In order to treat cancer progression, cancer immunotherapy is used to stimulate the immune system where immunosuppression is present in tumor microenvironments. Many cancer cells produce a lot of interleukin-6 (IL-6) and signal transducer activator of transcription 3 (STAT3). STAT3 plays a key role in suppressing the expression of critical immune activation regulators. IL‐6‐mediated STAT3 activation is common in the tumor microenvironment. Inhibiting the IL-6/STAT3 signaling pathway has become a therapeutic option for cancer progression. As vimentin is also expressed in hepatic stellate cells boosting cancer survival. We focused on the precise effect of extract from leaves of Azadirachta indica Juss, on inhibiting the IL-6/STAT3 signaling cascade on hepatocellular carcinoma by in vitro and in vivo study. Methods: In the in vitro study, the effect of Azadirachta indica Juss. variant Indonesia and Philippines against the expression of IL-6 and STAT3 was examined in liver cancer cell line. In the in vivo study, 24 male rats (Rattus norvegicus) strain Wistar were induced by diethylnitrosamine and carbon tetrachloride (CCl4). Based on the therapy given, the groups were divided into negative control, positive control, Indonesia extract, and Philippine extract. Expression of IL-6, STAT3, and vimentin were tested using immunohistochemistry staining. The data were analyzed using analysis of variance, which was then followed by the Tukey test. Results: Statistically significant difference in IL-6 and STAT3 was observed between the treatment groups and positive control group by in vitro study and in vivo study. Generally, there is no significant difference between treatment using Indonesian and Philippine leaves. Conclusion: Both therapy doses of Azadirachta indica variant in Indonesia and Philippines were able to reduce IL-6, STAT3 and vimentin expression of hepatocellular carcinoma cell by in vitro and in vivo experiment.
Critical delay factors for construction projects in Central Aceh District, Indonesia
Authors: Rauzana Anita , Zahrah Aghnia , Dharma Wira 
Published: April 2022

Background: Construction development in Indonesia is growing rapidly, especially in Central Aceh District. Construction projects have distinctive characteristics and are very complex, so that risk events can have a serious impact on the viability of the project. A lack of attention to the risks faced will affect project implementation by creating delays, resulting in losses. The purpose of this study was to (1) identify the risk factors that cause delays in construction projects and (2) determine those particular risk factors that have a greater influence on construction projects. The location of this research was Central Aceh District, Indonesia. Methods: The data in this study were primary data in the form of a questionnaire and secondary data obtained from the literature related to this particular type of research. Questionnaires were distributed to respondents, namely contractor companies located in the Central Aceh District. The questionnaires were distributed to determine respondents' opinions about the level of influence of risk factors causing project delays. We used a validity test, reliability test, and descriptive analysis for data processing. Results: Based on the results of the study from 47 respondents, the “very high influence” category (Mode=5) for the tool malfunction factor was chosen by 21 respondents (44.68%), cost estimation inaccuracy by 20 respondents (42.55%), increased work costs by 22 respondents (46.81%), implementation of new technologies by 25 respondents (53.19%), details, accuracy and conformity to specifications that are not appropriate by 20 respondents (42.55%), worker quarrels by 20 respondents (42.55%), poor project planning and management by 22 respondents (46.81%), poor condition at locations and accessibility difficulty by 20 respondents (42.55%). Conclusions: Of the 80 risk factors that caused project delays, eight risk factors were found to have a very high influence on the implementation of construction projects in Central Aceh District.
Characterization of sulfated polysaccharide activity against virulent Plasmodium falciparum PHISTb/RLP1 protein
Authors: Mutisya Jennifer M. , Mobegi Victor A. , Kinyua Johnson K. , Kivecu Martha N. , Okoth Raphael O. , Chemwor Gladys C. , Mwakio Edwin W. , Cheruiyot Agnes C. , Yeda Redempta A. , Okello Charles O. , Juma Jackline A. , Opot Benjamin H. , Juma Dennis W. , Roth Amanda L. , Akala Hosea M. , Andagalu Ben M. 
Published: April 2022

Background: The emergence of artemisinin resistance in South East Asia calls for urgent discovery of new drug compounds that have antiplasmodial activity. Unlike the classical compound screening drug discovery methods, the rational approach involving targeted drug discovery is less cumbersome and therefore key for innovation of new antiplasmodial compounds. Plasmodium falciparum (Pf) utilizes the process of host erythrocyte remodeling using Plasmodium-helical interspersed sub-telomeric domain (PHIST) containing proteins, which are amenable drug targets. The aim of this study is to identify inhibitors of PHIST from sulfated polysaccharides as new antimalarials. Methods: 251 samples from an ongoing study of epidemiology of malaria and drug resistance sensitivity patterns in Kenya were sequenced for PHISTb/RLP1 gene using Sanger sequencing. The sequenced reads were mapped to the reference Pf3D7 protein sequence of PHISTb/RLP1 using CLC Main Workbench. Homology modeling of both reference and mutant protein structures was achieved using the LOMETs tool. The models were refined using ModRefiner for energy minimization. Ramachandran plot was generated by ProCheck to assess the conformation of amino acids in the protein model. Protein binding sites predictions were assessed using FT SITE software. We searched for prospective antimalarials from PubChem. Docking experiments were achieved using AutoDock Vina and analysis results visualized in PyMOL. Results: Sanger sequencing generated 86 complete sequences. Upon mapping of the sequences to the reference, 12 non-synonymous single nucleotide polymorphisms were considered for mutant protein structure analysis. Eleven drug compounds with antiplasmodial activity were identified. Both modeled PHISTb/RLP1 reference and mutant structures had a Ramachandran score of >90% of the amino acids in the favored region. Ten of the drug compounds interacted with amino acid residues in PHISTb and RESA domains, showing potential activity against these proteins. Conclusion: This research identifies inhibitors of exported proteins that can be used in in vitro tests against the Plasmodium parasite.
Can forensic radiological skeletal age estimation be performed by examining ischiopubic-ilioischial-iliopubic synchondrosis in computed tomography images?
Authors: Gümüş Burak , Karavaş Erdal , Taydaş Onur 
Published: April 2022

Introduction
In this study, we evaluated whether it is possible to perform forensic radiological skeletal age estimation via radiological examination of the ilioischial, ischiopubic, and iliopubic synchondrosis regions of the pelvis.

Methods
This study was conducted by retrospectively examining the abdominopelvic images of individuals aged 8–16 who had applied to the hospital for any reason without having a chronic disorder and who had undergone computed tomography. Two radiologists retrospectively reviewed the images. The BT images of the pelvis ilioischial, ischiopubic, and iliopubic synchondrosis regions were evaluated as follows: 0: open, 1: semiclosed, and 2: closed. The data were evaluated using the SPSS 17 program.

Results
Two hundred sixty-three children (118 girls and 145 boys) between the ages of 8 and 16 years without any health problems participated. There was a significant difference between the groups for all the evaluated synchondrosis joints in girls and boys (p<0.001 for each group comparison). We observed that ilioischial, ischiopubic, and iliopubic synchondrosis closed earlier in girls than boys. In addition, we found that the joints were closed at the age of 15 and over in boys and at 14 and over in girls.

Discussion
Some studies have previously evaluated synchondrosis by using computed tomography. We showed that forensic radiological skeletal age estimation could be performed by examining ischiopubic-ilioischial-iliopubic synchondrosis in pelvis computed tomography images. The pelvis is more resistant to decay than other parts of the body. Furthermore, pelvis bones can withst and the effects of postmortem animal attacks for a longer period. Therefore, we believe that forensic age estimation can be made on corpses with no extremity, a damaged chest, or whose only pelvic bones are assessable through the method we use.

Conclusion
In our study, the ischiopubic-ilioischial-iliopubic joints were open in those aged nine and under and closed in those aged 15 and above. Ilioischial, ischiopubic, and iliopubic synchondrosis were observed to close earlier in girls than in boys. We consider that our study will be beneficial in the 8-16-year-old age group if used. In addition, our study can be used to determine the radiological bone age in cases with wrist bone abnormalities or wrist amputation.
Trans-radial approach versus trans-femoral approach in patients with acute coronary syndrome undergoing percutaneous coronary intervention: An updated meta-analysis of randomized controlled trials
Authors: Senguttuvan Nagendra Boopathy , Reddy Pothireddy M. K. , Shankar PunatiHari , Abdulkader Rizwan Suliankatchi , Yallanki Hanumath Prasad , Kumar Ashish , Majmundar Monil , Ramalingam Vadivelu , Rajendran Ravindran , Bhoopalan Kesavamoorthy , Kaliyamoorthy Dhamodharan , T. R. Muralidharan , Kalra Ankur , Jayaraj Ramamoorthi , Ramakrishnan Sivasubramanian , Daggubati Ramesh , Thanikachalam Sadagopan , Seth Ashok , Bahl Vinay Kumar 
Published: April 2022

Introduction
Trans-radial approach (TRA) is recommended over trans-femoral approach (TFA) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We intended to study the effect of access on all-cause mortality.

Methods and results
We searched PubMed and EMBASE for randomized studies on patients with ACS undergoing PCI. The primary outcome was all-cause mortality at 30-days. The secondary outcomes included in-hospital mortality, major adverse cardiac or cerebrovascular event (MACE) as defined by the study, net adverse clinical event (NACE), non-fatal myocardial infarction, non-fatal stroke, stent thrombosis, study-defined major bleeding, and minor bleeding, vascular complications, hematoma, pseudoaneurysm, non-access site bleeding, need for transfusion, access site cross-over, contrast volume, procedure duration, and hospital stay duration. We studied 20,122 ACS patients, including 10,037 and 10,085 patients undergoing trans-radial and trans-femoral approaches, respectively. We found mortality benefit in patients with ACS for the trans-radial approach [(1.7% vs. 2.3%; RR: 0.75; 95% CI: 0.62–0.91; P = 0.004; I2 = 0%). Out of 10,465 patients with STEMI, 5,189 patients had TRA and 5,276 had TFA procedures. A similar benefit was observed in patients with STEMI alone [(2.3% vs. 3.3%; RR: 0.71; 95% CI: 0.56–0.90; P = 0.004; I2 = 0%). We observed reduced MACE, NACE, major bleeding, vascular complications, and pseudoaneurysms. No difference in re-infarction, stroke, and serious bleeding requiring blood transfusions were noted. We noticed a small decrease in contrast volume(ml) {mean difference (95% CI): −4.6 [−8.5 to −0.7]}, small but significantly increase in procedural time {mean difference (95% CI) 1.2 [0.1 to 2.3]}and fluoroscopy time {mean difference (95% CI) 0.8 [0.3 to1.4] min} in the trans-radial group.

Conclusion
TRA has significantly reduced 30-day all-cause mortality among patients undergoing PCI for ACS. TRA should be the preferred vascular access in patients with ACS.
Expression of vimentin, TPI and MAT2A in human dermal microvascular endothelial cells during angiogenesis in vitro
Authors: Herre Christina , Nshdejan Arpenik , Klopfleisch Robert , Corte Giuliano Mario , Bahramsoltani Mahtab 
Published: April 2022

Introduction
In vitro assays of angiogenesis face immense problems considering their reproducibility based on the inhomogeneous characters of endothelial cells (ECs). It is necessary to detect influencing factors, which affect the angiogenic potency of ECs.

Objective
This study aimed to analyse expression profiles of vimentin (VIM), triosephosphate isomerase (TPI) and adenosylmethionine synthetase isoform type–2 (MAT2A) during the whole angiogenic cascade in vitro. Furthermore, the impact of knocking down vimentin (VIM) on angiogenesis in vitro was evaluated, while monitoring TPI and MAT2A expression.

Methods
A long–term cultivation and angiogenic stimulation of human dermal microvascular ECs was performed. Cells were characterized via VEGFR–1 and VEGFR–2 expression and a shRNA–mediated knockdown of VIM was performed. The process of angiogenesis in vitro was quantified via morphological staging and mRNA–and protein–levels of all proteins were analysed.

Results
While native cells ran through the angiogenic cascade chronologically, knockdown cells only entered beginning stages of angiogenesis and died eventually. Cell cultures showing a higher VEGFR–1 expression survived exclusively and displayed an upregulation of MAT2A and TPI expression. Native cells highly expressed VIM in early stages, MAT2A mainly in the beginning and TPI during the course of angiogenesis in vitro.

Conclusion
VIM knockdown led to a deceleration of angiogenesis in vitro and knockdown cells displayed expressional changes in TPI and MAT2A. Cell populations with a higher number of stalk cells emerged as being more stable against manipulations and native expression profiles provided an indication of VIM and MAT2A being relevant predominantly in beginning stages and TPI during the whole angiogenic cascade in vitro.
Remdesivir plus Dexamethasone in COVID-19: A cohort study of severe patients requiring high flow oxygen therapy or non-invasive ventilation
Authors: De Pascale Gennaro , Cutuli Salvatore Lucio , Carelli Simone , Xhemalaj Rikardo , Rosà Tommaso , Bello Giuseppe , Vargas Joel , Cesarano Melania , Montini Luca , Tanzarella Eloisa Sofia , Pintaudi Gabriele , Di Muro Mariangela , Grieco Domenico Luca , Antonelli Massimo 
Published: April 2022

Introduction
Remdesivir and Dexamethasone represent the cornerstone of therapy for critically ill patients with acute hypoxemic respiratory failure caused by Coronavirus Disease 2019 (COVID-19). However, clinical efficacy and safety of concomitant administration of Remdesivir and Dexamethasone (Rem-Dexa) in severe COVID-19 patients on high flow oxygen therapy (HFOT) or non-invasive ventilation (NIV) remains unknown.

Materials and methods
Prospective cohort study that was performed in two medical Intensive Care Units (ICUs) of a tertiary university hospital. The clinical impact of Rem-Dexa administration in hypoxemic patients with COVID-19, who required NIV or HFOT and selected on the simplified acute physiology score II, the sequential organ failure assessment score and the Charlson Comorbidity Index score, was investigated. The primary outcome was 28-day intubation rate; secondary outcomes were end-of-treatment clinical improvement and PaO2/FiO2 ratio, laboratory abnormalities and clinical complications, ICU and hospital length of stay, 28-day and 90-day mortality.

Results
We included 132 patients and found that 28-day intubation rate was significantly lower among Rem-Dexa group (19.7% vs 48.5%, p<0.01). Although the end-of-treatment clinical improvement was larger among Rem-Dexa group (69.7% vs 51.5%, p = 0.05), the 28-day and 90-day mortalities were similar (4.5% and 10.6% vs. 15.2% and 16.7%; p = 0.08 and p = 0.45, respectively). The logistic regression and Cox-regression models showed that concomitant Rem-Dexa therapy was associated with a reduction of 28-day intubation rate (OR 0.22, CI95% 0.05–0.94, p = 0.04), in absence of laboratory abnormalities and clinical complications (p = ns).

Conclusions
In COVID-19 critically ill patients receiving HFO or NIV, 28-day intubation rate was lower in patients who received Rem-Dexa and this finding corresponded to lower end-of-treatment clinical improvement. The individual contribution of either Remdesevir or Dexamethasone to the observed clinical effect should be further investigated.
Clinical course of patients with severe COVID-19 pneumonia treated with remdesivir: A real-life study
Authors: Tejada Diana , Juanbeltz Regina , Rivero María , San Miguel Ramón , Capdevila Ferrán , Beloqui Juan José , Sarobe Maite 
Published: April 2022

Background
There is currently much uncertainty regarding the most optimal treatment for COVID-19. This study analyze the change in the clinical condition of patients hospitalized for severe COVID-19 pneumonia and treated with remdesivir in a real-life setting, based on the WHO Ordinal Scale. Clinical complications, treatment safety, and impact of other associated drugs were also analyzed.

Methods
We conducted an observational, retrospective study including patients treated with remdesivir. The need for admission to the ICU, the length of ICU and hospital stay, and the need for ventilatory support were analyzed. The laboratory parameters, drugs administered concomitantly, and difference in the length of hospital stay according to the concomitant treatment received were also evaluated. A univariate and multivariate Cox regression analysis was performed to analyze associated factors.

Results
A total of 92 patients were included. The mean length of hospital stay was 15 days, and 90% of the patients had been discharged from the hospital 28 days after starting treatment with remdesivir. The likelihood of hospital discharge among patients not presenting with hypertension as a comorbidity was significantly higher than that of those with this condition (HR = 3.19, P = 0.008). Nineteen patients had to be admitted to the ICU (mean of 18 days). Approximately 11% required invasive mechanical ventilation (mean of 22 days). Almost 37% of the patients received high-flow oxygen therapy and 14% non-invasive mechanical ventilation. Four deaths were recorded within the first week. Main adverse events were increases in transaminase and creatinine levels. Nosocomial infections were more frequent when remdesivir was combined with immunosuppressive drugs.

Conclusions
Patients with severe COVID-19 pneumonia and treated with remdesivir require relatively prolonged hospital stays, many with a need for ventilatory support and, in a considerable proportion of cases, admission to the ICU. However, the observed survival rate is high, and the drug is well tolerated.