bluuebunny/crossref_metadata_2025 huggingface dataset:
An Analysis of the Optimal Facility Location of Tourism Industry in Plain Region by Utilizing GIS
Authors: Chen Yen-Chieh , Yao Hsiao-Li , Weng Shou-Der , Tai Yang-Fei
Published: April 2022

In this study, we utilize regional public facilities as the factors of evaluation criteria, apply buffering and weighted overlay analysis in GIS as the multi-criteria spatial information analysis tools, and take the Lanyang Plain, Yilan, Taiwan as the test area for the optimal facility location analysis of tourism industry. We take the “optimal service/influence distance” of each regional public facility from literature review as the radius of neighborhood for buffering and build the buffer objects in GIS. The process of weighted overlay analysis is conducted by using grid method. After a series of grid size testing, we find that while the grid size decreases to 320 m × 320 m, the distribution of grids with weighted overlay values is close to the distribution of all the buffer objects mentioned above. The distribution of grids with higher weighted overlap values obviously presents the optimal facility location of tourism industry that is apparently consistent with the distribution of the famous tour sites or facilities of tourism industry and the four to five star hotels. Therefore, we conclude that this optimal facility location model of tourism industry should be quite suitable for land use or site selection planning of tourism and relative industries.
Challenges and Support in Article Publication: Perspectives of Non-Native English Speaking Doctoral Students in a “Publish or No Degree” Context
Authors: Shamsi Ahmad Fawzi , Osam Ulker Vanci
Published: April 2022

Article publication as a requirement for graduation appears to be the most compelling challenge for doctoral candidates, especially for the non-English speaking ones. In order to contribute to this topic of growing interest, we aimed to investigate the key challenges to doctoral student research publication and develop an understanding of support they needed to ease the publication process. To this end, we conducted semi-structured interviews with 19 non-English speaking doctoral students in varied science and social science programs at an international university in north Cyprus. The findings revealed that the participants supported the “publish or no degree” policy as a condition for their graduation despite several challenges it created for them, such as lack of publication experience, weaknesses in the article composition, tough criteria of journals, and inadequate support from the instructors at the course phase. Peer-support community among the doctoral students lacked in the examined context and promoting it might yield positive results.
Patient-identified burden and unmet needs in patients with cluster headache: An evidence-based qualitative literature review
Authors: Freeman Emily , Adair Michael , Beeler Dori , Casper Rozanne , Herman Melissa P , Reeves David , Reinsch Stefan
Published: April 2022

Objectives:

To qualitatively identify evidence-based literature related to the daily burden and unmet treatment and psychosocial needs of patients with cluster headache (CH).

Methods:

A literature search was conducted through October 20, 2020 across MEDLINE, EMBASE, CINAHL, and PsychInfo databases exploring quality of life (QoL) and disease burden in adults with CH. The search was restricted to full-text reports in peer-reviewed journals. Methodologic quality was assessed using the Critical Skills Appraisal Program.

Results:

From 11 identified publications, QoL was reduced in persons living with CH, with significant psychological, social, and socio-economic burdens, and work-related disability. The CH disease trajectory is complex, with patients experiencing the impact of their disease across multiple domains beyond the biological manifestation of the disease including stigma, employment limitations, and suicidal ideation, and with a lack of effective treatment from the patient perspective.

Discussion:

These findings strengthen comprehension of the CH patient experience, enabling a deeper understanding of the patients’ perspective and experience of their disease andunmet needs, providing a basis for future research into this debilitating condition. Minor limitations of this study include data extraction and study selection biases.
Improving the anthocyanin accumulation of hypocotyls in radish sprouts by hemin-induced NO
Authors: Su Nana , Liu Ze , Wang Lu , Liu Yuanyuan , Niu Mengyang , Chen Xin , Cui Jin
Published: April 2022

Background

The health benefits of anthocyanins impel researchers and food producers to explorer new methods to increase anthocyanin contents in plant foods. Our previous studies revealed a positive role of nitric oxide (NO) in anthocyanin accumulation in radish (Raphanus sativus L.) sprouts. The application of hemin, an inducer of heme oxygenase-1 (HO-1), can effectively elevate NO production in vivo. Hemin treatment also improves plant growth and stress tolerance. This study is aimed to assess the effects of hemin treatment on anthocyanin production in radish sprouts, and to investigate whether NO signalling is involved in this process.

Results

The application of hemin significantly up regulated the expressions of many anthocyanins biosynthesis related structure and regulatory genes, leading to increased anthocyanins accumulation in radish hypocotyls. Hemin treatment also raised NO contents in radish sprouts, probably through enhancing nitrate reductase (NR) activity and Nitric Oxide-Associated 1 (NOA1) expression. Comparing the effects of Zinc Protoporphyrin (ZnPP, HO-1 activity inhibitor), Sodium Nitroprusside (SNP, NO donor) and carboxy-PTIO (cPTIO, NO-scavenger) on anthocyanin and NO production, a positive role of NO signalling has been revealed in hemin-derived anthocyanin accumulation. A positive feedback loop between HO-1 and NO may be involved in regulating this process.

Conclusions

Hemin induced anthocyanin accumulation in radish sprouts through HO-1 and NO signalling network.
Pseudogenization of the rhizobium-responsive EXOPOLYSACCHARIDE RECEPTOR in Parasponia is a rare event in nodulating plants
Authors: Dupin Simon , Klein Joël , Rutten Luuk , Huisman Rik , Geurts Rene
Published: April 2022

Background

Nodule symbiosis with diazotrophic Frankia or rhizobium occurs in plant species belonging to ten taxonomic lineages within the related orders Fabales, Fagales, Cucurbitales, and Rosales. Phylogenomic studies indicate that this nitrogen-fixing nodulation trait has a single evolutionary origin. In legume model plants, the molecular interaction between plant and rhizobium microsymbiont is mapped to a significant degree. A specific LysM-type receptor kinase, LjEPR3 in Lotus japonicus and MtLYK10 in Medicago truncatula, was found to act in a secondary identity-based mechanism, controlling intracellular rhizobium infection. Furthermore, LjEPR3 showed to bind surface exopolysaccharides of Mesorhizobium loti, the diazotrophic microsymbiont of L. japonicus. EPR3 orthologous genes are not unique to legumes. Surprisingly, however, its ortholog EXOPOLYSACCHARIDE RECEPTOR (EPR) is pseudogenized in Parasponia, the only lineage of non-legume plants that nodulate also with rhizobium.

Results

Analysis of genome sequences showed that EPR3 orthologous genes are highly conserved in nodulating plants. We identified a conserved retrotransposon insertion in the EPR promoter region in three Parasponia species, which associates with defected transcriptional regulation of this gene. Subsequently, we studied the EPR gene of two Trema species as they represent the sister genus of Parasponia for which it is assumed it lost the nitrogen-fixing nodulation trait. Both Trema species possess apparently functional EPR genes that have a nodulation-specific expression profile when introduced into a Parasponia background. This indicates the EPR gene functioned in nodulation in the Parasponia-Trema ancestor.

Conclusion

We conclude that nodule-specific expression of EPR3 orthologous genes is shared between the legume and Parasponia-Trema lineage, suggesting an ancestral function in the nitrogen-fixing nodulation trait. Pseudogenization of EPR in Parasponia is an exceptional case in nodulating plants. We speculate that this may have been instrumental to the microsymbiont switch -from Frankia to rhizobium- that has occurred in the Parasponia lineage and the evolution of a novel crack entry infection mechanism.
Computed tomography scan measurements of the globe and orbit to assess the risks of traumatic complications from medial peribulbar anaesthesia
Authors: Clarke Jon , Seah Huey Ming , Foo Aaron , Agzarian Marc , Lake Stewart
Published: April 2022

Complications of peribulbar anaesthesia include retrobulbar haemorrhage, globe perforation and brainstem anaesthesia. Therefore, this study took measurements relating the proximity of medial canthus to the optic nerve and also the safe angle between orbit and globe using 200 multiplanar reconstructed computed tomography (CT) images of the orbit. The principal results show that in 1.5% of the sample, the optic nerve is within 20 mm of the medial canthus, with a minimum distance of 15 mm. One% have a safe angle of 10 degrees or less between bone and globe. None of the demographic data, nor axial length were predictive of these results. We have shown that there are a minority of patients with unusual orbital anatomy. This places them at a theoretical higher risk of complications. These cases are not currently predicted by measured data.
The efficacy of deep learning models in the diagnosis of endometrial cancer using MRI: a comparison with radiologists
Authors: Urushibara Aiko , Saida Tsukasa , Mori Kensaku , Ishiguro Toshitaka , Inoue Kei , Masumoto Tomohiko , Satoh Toyomi , Nakajima Takahito
Published: May 2022

Purpose

To compare the diagnostic performance of deep learning models using convolutional neural networks (CNN) with that of radiologists in diagnosing endometrial cancer and to verify suitable imaging conditions.

Methods

This retrospective study included patients with endometrial cancer or non-cancerous lesions who underwent MRI between 2015 and 2020. In Experiment 1, single and combined image sets of several sequences from 204 patients with cancer and 184 patients with non-cancerous lesions were used to train CNNs. Subsequently, testing was performed using 97 images from 51 patients with cancer and 46 patients with non-cancerous lesions. The test image sets were independently interpreted by three blinded radiologists. Experiment 2 investigated whether the addition of different types of images for training using the single image sets improved the diagnostic performance of CNNs.

Results

The AUC of the CNNs pertaining to the single and combined image sets were 0.88–0.95 and 0.87–0.93, respectively, indicating non-inferior diagnostic performance than the radiologists. The AUC of the CNNs trained with the addition of other types of single images to the single image sets was 0.88–0.95.

Conclusion

CNNs demonstrated high diagnostic performance for the diagnosis of endometrial cancer using MRI. Although there were no significant differences, adding other types of images improved the diagnostic performance for some single image sets.
Assessment of the mental workload of trainee pilots of remotely operated aircraft using functional near-infrared spectroscopy
Authors: Tang Liya , Si Juanning , Sun Lei , Mao Gengsheng , Yu Shengyuan
Published: April 2022

Background

Operating an aircraft is associated with a large mental workload; however, knowledge of the mental workload of ROV operators is limited. The purpose of this study was to establish a digital system for assessing the mental workload of remotely operated vehicle (ROV) operators using hemodynamic parameters, and compare results of different groups with different experience levels.

Method

Forty-one trainee pilots performed flight tasks once daily for 5 consecutive days in a flight simulation. Forty-five pilots experienced pilots and 68 experienced drivers were also included. Hemodynamic responses were measured by functional near-infrared spectroscopy (fNIRS).

Results

The median duration of peak oxyhemoglobin was 147.13 s (interquartile range [IQR] 21.97, 401.70 s) in the left brain and 180.74 s (IQR 34.37, 432.01 s) in the right brain in the experienced pilot group, and 184.42 s (IQR 3.41, 451.81 s) on day 5 in the left brain and 160.30 s (IQR 2.62, 528.20 s) in the right brain in the trainee group.

Conclusion

Navigation training reduces peak oxyhemoglobin duration, and may potentially be used as a surrogate marker for mental workload of ROV operators. Peak oxyhemoglobin concentration during s task may allow development of a simplified scheme for optimizing flight performance based on the mental workload of a pilot.
Associations of severe adverse perinatal outcomes among continuous birth weight percentiles on different birth weight charts: a secondary analysis of a cluster randomized trial
Authors: Kamphof Hester D. , Gordijn Sanne J. , Ganzevoort Wessel , Verfaille Viki , Offerhaus Pien M. , Franx Arie , Pajkrt Eva , de Jonge Ank , Henrichs Jens
Published: April 2022

Objective

To identify neonatal risk for severe adverse perinatal outcomes across birth weight centiles in two Dutch and one international birth weight chart.

Background

Growth restricted newborns have not reached their intrinsic growth potential in utero and are at risk of perinatal morbidity and mortality. There is no golden standard for the confirmation of the diagnosis of fetal growth restriction after birth. Estimated fetal weight and birth weight below the 10thpercentile are generally used as proxy for growth restriction. The choice of birth weight chart influences the specific cut-off by which birth weight is defined as abnormal, thereby triggering clinical management. Ideally, this cut-off should discriminate appropriately between newborns at low and at high risk of severe adverse perinatal outcomes and consequently correctly inform clinical management.

Methods

This is a secondary analysis of the IUGR Risk Selection (IRIS) study. Newborns (n = 12 953) of women with a low-risk status at the start of pregnancy and that received primary antenatal care in the Netherlands were included.

We examined the distribution of severe adverse perinatal outcomes across birth weight centiles for three birth weight charts (Visser, Hoftiezer and INTERGROWTH) by categorizing birth weight centile groups and comparing the prognostic performance for severe adverse perinatal outcomes.

Severe adverse perinatal outcomes were defined as a composite of one or more of the following: perinatal death, Apgar score < 4 at 5 min, impaired consciousness, asphyxia, seizures, assisted ventilation, septicemia, meningitis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, or necrotizing enterocolitis.

Results

We found the highest rates of severe adverse perinatal outcomes among the smallest newborns (< 3rdpercentile) (6.2% for the Visser reference curve, 8.6% for the Hoftiezer chart and 12.0% for the INTERGROWTH chart). Discriminative abilities of the three birth weight charts across the entire range of birth weight centiles were poor with areas under the curve ranging from 0.57 to 0.61. Sensitivity rates of the various cut-offs were also low.

Conclusions

The clinical utility of all three charts in identifying high risk of severe adverse perinatal outcomes is poor. There is no single cut-off that discriminates clearly between newborns at low or high risk.

Trial Registration

Netherlands Trial RegisterNTR4367.

Registration date March 20th, 2014.
High risk of adverse birth outcomes among adolescents living with HIV in Botswana compared to adult women living with HIV and adolescents without HIV
Authors: Jackson-Gibson Maya , Zash Rebecca , Mussa Aamirah , Caniglia Ellen C. , Diseko Modiegi , Mayondi Gloria , Mabuta Judith , Morroni Chelsea , Mmalane Mompati , Lockman Shahin , Makhema Joseph , Shapiro Roger L.
Published: April 2022

Background

Adolescent girls are three times more likely to be living with HIV than boys of the same age. Prior studies have found associations between adolescent pregnancies and increased maternal morbidity and infant mortality, but few studies have assessed the impact of HIV infection on maternal and infant outcomes in adolescents.

Methods

The Tsepamo Study abstracts maternal and infant data from obstetric records in government maternity wards in Botswana. We assessed maternal complications and adverse birth outcomes for all singleton pregnancies from August 2014 to August 2020 at eighteen Tsepamo sites among adolescents (defined as 10–19 years of age) and adults (defined as 20–35 years of age), by HIV status. Univariate and multivariate logistic regression using a complete case analysis method were used to evaluate differences in outcomes.

Results

This analysis included 142,258 singleton births, 21,133 (14.9%) to adolescents and 121,125 (85.1%) to adults. The proportion of adults living with HIV (N = 22,114, 22.5%) was higher than adolescents (N = 1593, 7.6%). The proportion of most adverse birth outcomes was higher in adolescents. Among adolescents, those with HIV had increased likelihoods of anemia (aOR = 1.89, 95%CI 1.66, 2.15) and cesarean sections (aOR = 1.49, 95%CI 1.3,1.72), and infants with preterm birth (aOR = 1.15, 95%CI 1.0, 1.32), very preterm birth (aOR = 1.35, 95%CI 1.0,1.8), small for gestational age (aOR = 1.37, 95%CI 1.20,1.58), and very small for gestational age (aOR = 1.46, 95%CI 1.20, 1.79).

Conclusions

Adolescent pregnancy and adolescent HIV infection remain high in Botswana. Adolescents have higher risk of adverse maternal and infant birth outcomes than adults, with the worst outcomes among adolescents living with HIV. Linking HIV prevention and family planning strategies for this age group may help minimize the number of infants with poor birth outcomes among this already vulnerable population.
LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway
Authors: Tan Yuen , Chen Qingchuan , Pan Siwei , An Wen , Xu Huimian , Xing Yao , Zhang Jianjun
Published: April 2022

Background

The Lauren classification of gastric tumors strongly correlates with prognosis. The purpose of this study was to explore the specific molecular mechanism of Lauren classification of gastric cancer and provide a possible theoretical basis for the treatment of gastric cancer.

Methods

We standardized the gene expression data of five Gene Expression Omnibus gastric cancer databases and constructed a Weighted Co-expression Network Analysis (WGCNA) model based on clinicopathological information. The overall survival (OS) and disease-free survival (DFS) curves were extracted from the Cancer Genome Atlas (TCGA) and GSE62254 databases. Western blotting was used to measure protein expression in cells and tissues. Scratch and transwell experiments were used to test the migration ability of tumor cells. Immunohistochemistry was used to measure tissue protein expression in clinical tissue samples to correlate to survival data.

Results

The WGCNA model demonstrated that blue cyan was highly correlated with the Lauren classification of the tumor (r = 0.24, P = 7 × 1016). A protein-protein interaction network was used to visualize the genes in the blue cyan module. The OS and PFS TCGA analysis revealed that LMOD1 was a gene of interest. The proportion of diffuse gastric cancer patients with high expression of LMOD1 was significantly higher than that of intestinal type patients. LMOD1 promoted the migration of gastric cancer cells by regulating the FAK-Akt/mTOR pathway in vitro. Additionally, a Gene Set Enrichment Analysis using the TCGA and GSE62254 databases, and western blot data, showed that LMOD1 could promote an epithelial-mesenchymal transition (EMT), thus potentially affecting the occurrence of peritoneal metastasis of gastric cancer. Immunohistochemistry showed that LMOD1 was highly expressed in cancer tissues, and the prognosis of patients with high LMOD1 expression was poor.

Conclusion

LMOD1 is an oncogene associated with diffuse gastric cancer and can affect the occurrence and development of EMT by regulating the FAK-Akt/mTOR pathway. LMOD1 can therefore promote peritoneal metastasis of gastric cancer cells and can be used as a novel therapeutic target for gastric cancer.
Novel type of references for BMI aligned for onset of puberty – using the QEPS growth model
Authors: Albertsson-Wikland Kerstin , Niklasson Aimon , Gelander Lars , Holmgren Anton , Nierop Andreas F. M.
Published: April 2022

Objectives

Despite inter-individual variations in pubertal timing, growth references are conventionally constructed relative to chronological age (C-age). Thus, they are based on reference populations containing a mix of prepubertal and pubertal individuals, making them of limited use for detecting abnormal growth during adolescence. Recently we developed new types of height and weight references, with growth aligned to age at onset of the pubertal growth spurt (P-age). Here, we aim to develop a corresponding reference for pubertal BMI.

Methods

The QEPS-height and weight models were used to define a corresponding QEPS-BMI model. QEPS-BMI was modified by the same individual, constitutional weight–height-factor (WHF) as computed for QEPS-weight. QEPS-BMI functions were computed with QEPS weight and height functions fitted on longitudinal measurements from 1418 individuals (698 girls) from GrowUp1990Gothenburg cohort. These individual BMI functions were used to develop BMI references aligned for height at AgeP5; when 5% of specific puberty-related (P-function) height had been attained. Pubertal timing, stature at pubertal onset, and childhood BMI, were investigated in subgroups of children from the cohort GrowUp1974Gothenburg using the new references.

Results

References (median, standard deviation score (SDS)) were generated for total BMI (QEPS-functions), for ongoing prepubertal growth (QE-function) vs C-age, and for total BMI and separated into BMI specific to puberty (P-function) and BMI gain from ongoing basic growth (QES-functions), allowing individual growth to be aligned based on P-age. Growth in basic BMI was greater than average for children categorized as tall and/or with high-BMI at puberty-start. In children categorized as short at puberty-start, P-function-related-BMI was greater than average.

Conclusions

Use of these new pubertal BMI references will make it possible for the first time to consider individual variations owing to pubertal timing when evaluating BMI. This will improve the detection of abnormal changes in body composition when used in combination with pubertal height and weight references also abnormal growth. Other benefits in the clinic will include improved growth monitoring during treatment for children who are overweight/obese or underweight. Furthermore, in research settings these new references represent a novel tool for exploring human growth.
Self-reported mental health during the COVID-19 pandemic and its association with alcohol and cannabis use: a latent class analysis
Authors: Somé Nibene Habib , Wells Samantha , Felsky Daniel , Hamilton Hayley A. , Ali Shehzad , Elton-Marshall Tara , Rehm Jürgen
Published: April 2022

Background

Mental health problems and substance use co-morbidities during and after the COVID-19 pandemic are a public health priority. Identifying individuals at high-risk of developing mental health problems and potential sequela can inform mitigating strategies. We aimed to identify distinct groups of individuals (i.e., latent classes) based on patterns of self-reported mental health symptoms and investigate their associations with alcohol and cannabis use.

Methods

We used data from six successive waves of a web-based cross-sectional survey of adults aged 18 years and older living in Canada (6,021 participants). We applied latent class analysis to three domains of self-reported mental health most likely linked to effects of the pandemic: anxiety, depression, and loneliness. Logistic regression was used to characterize latent class membership, estimate the association of class membership with alcohol and cannabis use, and perform sex-based analyses.

Results

We identified two distinct classes: (1) individuals with low scores on all three mental health indicators (no/low-symptoms) and (2) those reporting high scores across the three measures (high-symptoms). Between 73.9 and 77.1% of participants were in the no/low-symptoms class and 22.9–26.1% of participants were in the high-symptom class. We consistently found across all six waves that individuals at greater risk of being in the high-symptom class were more likely to report worrying about getting COVID-19 with adjusted odds ratios (aORs) between 1.72 (95%CI:1.17–2.51) and 3.51 (95%CI:2.20–5.60). Those aged 60 + were less likely to be in this group with aORs (95%CI) between 0.26 (0.15–0.44) and 0.48 (0.29–0.77) across waves. We also found some factors associated with class membership varied at different time points. Individuals in the high-symptom class were more likely to use cannabis at least once a week (aOR = 2.28, 95%CI:1.92–2.70), drink alcohol heavily (aOR = 1.71, 95%CI:1.49–1.96); and increase the use of cannabis (aOR = 3.50, 95%CI:2.80–4.37) and alcohol (aOR = 2.37, 95%CI:2.06–2.74) during the pandemic. Women in the high-symptom class had lower odds of drinking more alcohol during the pandemic than men.

Conclusions

We identified the determinants of experiencing high anxiety, depression, and loneliness symptoms and found a significant association with alcohol and cannabis consumption. This suggests that initiatives and supports are needed to address mental health and substance use multi-morbidities.
Civic engagement and psychological distress during the COVID-19 pandemic
Authors: Topazian Rachel J. , Levine Adam S. , McGinty Emma E. , Barry Colleen L. , Han Hahrie
Published: May 2022

Background

To examine the relationship between civic association participation and psychological distress during the COVID-19 pandemic, particularly whether different forms of engagement mitigate the increased rates of psychological distress throughout 2020.

Methods

Panel survey data collected from a nationally representative cohort of 1222 U.S. adults. Data was collected in three waves in April, July, and November 2020. Psychological distress was measured using the validated Kessler-6 instrument in November 2020.

Results

Respondents belonging to political associations were more likely to experience psychological distress (difference in predicted level of psychological distress on a 0-1 scale: 0.098, p ≤ .05) relative to those in unknown associations. However, individuals in political associations who more frequently interacted with others had lower levels of psychological distress (−.065, p ≤ .05) compared to those in political associations with less frequent interactions.

Conclusions

Civic engagement that facilitates interpersonal interactions may protect against psychological distress.
NPM2 in malignant peritoneal mesothelioma: from basic tumor biology to clinical medicine
Authors: Wu He-liang , Yang Zhi-ran , Yan Li-jun , Su Yan-dong , Ma Ru , Li Yan
Published: April 2022

Background

This review systematically summarizes gene biology features and protein structure of nucleoplasmin2 (NPM2) and the relationship between NPM2 and malignant peritoneal mesothelioma (MPM), in order to explore the molecular pathological mechanism of MPM and explore new therapeutic targets.

Methods

NCBI PubMed database was used for the literature search. NCBI Gene and Protein databases, Ensembl Genome Browser, UniProt, and RCSB PDB database were used for gene and protein review. Three online tools (Consurf, DoGSiteScorer, and ZdockServer), the GEPIA database, and the Cancer Genome Atlas were used to analyze bioinformatics characteristics for NPM2 protein.

Results

The main structural domains of NPM2 protein include the N-terminal core region, acidic region, and motif and disordered region. The N-terminal core region, involved in histone binding, is the most conserved domain in the nucleoplasmin (NPM) family. NPM2 with a large acidic tract in its C-terminal tail (NPM2-A2) is able to bind histones and form large complexes. Bioinformatics results indicated that NPM2 expression was correlated with the pathology of multiple tumors. Among mesothelioma patients, 5-year survival of patients with low-NPM2-expression was significantly higher than that of the high-NPM2-expression patients. NPM2 can facilitate the formation of histone deacetylation. NPM2 may promote histone deacetylation and inhibit the related-gene transcription, thus leading to abnormal proliferation, invasion, and metastasis of MPM.

Conclusion

NPM2 may play a key role in the development and progression of MPM.
CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies
Authors: Bruno Samantha , Ghelli Luserna di Rorà Andrea , Napolitano Roberta , Soverini Simona , Martinelli Giovanni , Simonetti Giorgia
Published: April 2022

Cell division cycle 20 homologue (CDC20) is a well-known regulator of cell cycle, as it controls the correct segregation of chromosomes during mitosis. Many studies have focused on the biological role of CDC20 in cancer development, as alterations of its functionality have been linked to genomic instability and evidence demonstrated that high CDC20 expression levels are associated with poor overall survival in solid cancers. More recently, novel CDC20 functions have been demonstrated or suggested, including the regulation of apoptosis and stemness properties and a correlation with immune cell infiltration. Here, we here summarize and discuss the role of CDC20 inside and outside mitosis, starting from its network of interacting proteins. In the last years, CDC20 has also attracted more interest in the blood cancer field, being overexpressed and showing an association with prognosis both in myeloid and lymphoid malignancies. Preclinical findings showed that selective CDC20 and APC/CCDC20/APC/CCDH1 inhibitors, namely Apcin and proTAME, are effective against lymphoma and multiple myeloma cells, resulting in mitotic arrest and apoptosis and synergizing with clinically-relevant drugs. The evidence and hypothesis presented in this review provide the input for further biological and chemical studies aiming to dissect novel potential CDC20 roles and targeting strategies in hematological malignancies.
The MYCN inhibitor BGA002 restores the retinoic acid response leading to differentiation or apoptosis by the mTOR block in MYCN-amplified neuroblastoma
Authors: Lampis Silvia , Raieli Salvatore , Montemurro Luca , Bartolucci Damiano , Amadesi Camilla , Bortolotti Sonia , Angelucci Silvia , Scardovi Anna Lisa , Nieddu Giammario , Cerisoli Lucia , Paganelli Francesca , Valente Sabrina , Fischer Matthias , Martelli Alberto Maria , Pasquinelli Gianandrea , Pession Andrea , Hrelia Patrizia , Tonelli Roberto
Published: April 2022

Background

Neuroblastoma is a deadly childhood cancer, and MYCN-amplified neuroblastoma (MNA-NB) patients have the worst prognoses and are therapy-resistant. While retinoic acid (RA) is beneficial for some neuroblastoma patients, the cause of RA resistance is unknown. Thus, there remains a need for new therapies to treat neuroblastoma. Here we explored the possibility of combining a MYCN-specific antigene oligonucleotide BGA002 and RA as therapeutic approach to restore sensitivity to RA in NB.

Methods

By molecular and cellular biology techniques, we assessed the combined effect of the two compounds in NB cell lines and in a xenograft mouse model MNA-NB.

Results

We found that MYCN-specific inhibition by BGA002 in combination with RA (BGA002-RA) act synergistically and overcame resistance in NB cell lines. BGA002-RA also reactivated neuron differentiation (or led to apoptosis) and inhibited invasiveness capacity in MNA-NB. Moreover, we found that neuroblastoma had the highest level of mRNA expression of mTOR pathway genes, and that BGA002 led to mTOR pathway inhibition followed by autophagy reactivation in MNA-NB cells, which was strengthened by BGA002-RA. BGA002-RA in vivo treatment also eliminated tumor vascularization in a MNA-NB mouse model and significantly increased survival.

Conclusion

Taken together, MYCN modulation mediates the therapeutic efficacy of RA and the development of RA resistance in MNA-NB. Furthermore, by targeting MYCN, a cancer-specific mTOR pathway inhibition occurs only in MNA-NB, thus avoiding the side effects of targeting mTOR in normal cells. These findings warrant clinical testing of BGA002-RA as a strategy for overcoming RA resistance in MNA-NB.
Impact of neoadjuvant chemotherapy on somatic mutation status in high-grade serous ovarian carcinoma
Authors: Marchocki Zibi , Tone Alicia , Virtanen Carl , de Borja Richard , Clarke Blaise , Brown Theodore , May Taymaa
Published: May 2022

Background

Patients treated with neoadjuvant chemotherapy (NACT) for advanced high-grade serous ovarian carcinoma (HGSC) have a higher rate and shorter time to platinum-resistant recurrence compared to patients treated with primary cytoreductive surgery (PCS) and adjuvant chemotherapy. The purpose of this study is to determine the impact of NACT on somatic mutation status in platinum-sensitive and resistant HGSC. Patients with advanced HGSC who had a documented response to platinum-based NACT, a banked blood sample, and a banked tumor sample before and after NACT were identified. Whole exome and/or targeted deep sequencing was performed in matched normal and pre/post-NACT tumor samples from 3 platinum-resistant and 2 platinum-sensitive patients to identify somatic non-synonymous mutations at each time point.

Results

When comparing exonic non-synonymous mutations in pre-NACT and post-NACT samples from the same patient, an average of 41% (1-68%) of genes were mutated at both time points. There were no trends detected in the mutational burden following exposure to NACT in platinum-resistant vs. platinum-sensitive cases. The majority of mutated genes were unique to each case. We identified several genes that were commonly mutated in pre-NACT samples specific to platinum-resistant (CSPG4, SLC35G5, TUBA3D) or sensitive (CYP2D6, NUTM1, DNAH5) cases. Four mutated genes emerged exclusively in the platinum-resistant cases (ADGRV1, MUC17, MUC20, PAK2) following NACT.

Conclusions

Patients with advanced HGSC present with significant intra-tumor heterogeneity. NACT significantly impacts the somatic mutation status irrespective of the time to recurrence. The mutated genes detected in chemo-naive pre-NACT tumor samples from either resistant or sensitive cases could potentially have a role in the prediction of chemotherapy response in patients scheduled to receive NACT; larger studies are required to further validate these genes.
Associations between measures of physical fitness and cognitive performance in preschool children
Authors: Wick Kristin , Kriemler Susi , Granacher Urs
Published: May 2022

Background

Given that recent studies report negative secular declines in physical fitness, associations between fitness and cognition in childhood are strongly discussed. The preschool age is characterized by high neuroplasticity which effects motor skill learning, physical fitness, and cognitive development. The aim of this study was to assess the relation of physical fitness and attention (including its individual dimensions (quantitative, qualitative)) as one domain of cognitive performance in preschool children. We hypothesized that fitness components which need precise coordination compared to simple fitness components are stronger related to attention.

Methods

Physical fitness components like static balance (i.e., single-leg stance), muscle strength (i.e., handgrip strength), muscle power (i.e., standing long jump), and coordination (i.e., hopping on one leg) were assessed in 61 healthy children (mean age 4.5 ± 0.6 years; girls n = 30). Attention was measured with the “Konzentrations-Handlungsverfahren für Vorschulkinder” [concentration-action procedure for preschoolers]). Analyses were adjusted for age, body height, and body mass.

Results

Results from single linear regression analysis revealed a significant (p < 0.05) association between physical fitness (composite score) and attention (composite score) (standardized ß = 0.40), showing a small to medium effect (F2 = 0.14). Further, coordination had a significant relation with the composite score and the quantitative dimension of attention (standardized ß = 0.35; p < 0.01; standardized ß =  − 0.33; p < 0.05). Coordination explained about 11% (composite score) and 9% (quantitative dimension) of the variance in the stepwise multiple regression model.

Conclusion

The results indicate that performance in physical fitness, particularly coordination, is related to attention in preschool children. Thus, high performance in complex fitness components (i.e., hopping on one leg) tends to predict attention in preschool children. Further longitudinal studies should focus on the effectiveness of physical activity programs implementing coordination and complex exercises at preschool age to examine cause-effect relationships between physical fitness and attention precisely.
Attachment-based parent–adolescent interaction linked to visual attention and autonomic arousal to distress and comfort stimuli
Authors: Schneider Marie , Obsuth Ingrid , Szymanska Monika , Mathieu Julie , Nezelof Sylvie , Lyons-Ruth Karlen , Vulliez-Coady Lauriane
Published: May 2022

In infancy and in the early years of life, emotion regulation and attachment relationships with parents are tightly intertwined. However, whether this link persists into adolescence has not yet been established and requires exploration. This pilot study utilizes an experimental design to assess the patterns of parent–adolescent interactions that are hypothesised to be related to two specific aspects of adolescents’ emotion regulation, namely: visual attention and autonomic arousal to distress and comfort stimuli. Two innovative and ecologically valid methodologies were utilized to assess (a) patterns of attachment-based parent–adolescent interactions among 39 adolescent–parent dyads from the general population, using the Goal-corrected Partnership in Adolescence Coding System (Lyons-Ruth et al. Goal corrected partnership in adolescence coding system (GPACS), 2005) applied to a conflict discussion task; (b) the two aspects of adolescent emotion regulation were assessed with the Visual/Autonomic Regulation of Emotions Assessment (VAREA) (Vulliez-Coady et al. Visual/Autonomic Regulation of Emotions Assessment, VAREA) paradigm, an attachment-related, emotionally arousing experimental procedure, using a distress-then-comfort paradigm, in conjunction to an eye-tracker synchronized with a physiological device that measured gaze and skin conductance response, (SCR), or emotional reactivity. In line with research in infancy, as predicted, markers of secure parent–adolescent interaction were linked to higher amplitude of SCR for distress and comfort pictures, and with longer attention to comfort pictures. On the other hand, parental role-confusion was associated with less time spent on comfort pictures by the adolescent. Overall, this pilot study suggests that interventions supporting collaborative communication between adolescents and their parents, as well as working to reduce parental role-confusion, may improve adaptive adolescent emotion regulation as assessed via physiological measures.
Vertical growth pattern as a determinant of mandibular asymmetry
Authors: Habib Maria , Ahsan Tabassum , Majeed Omair , Faheem Faisal
Published: April 2022

Objectives: To determine normal mandibular linear values in three vertical groups, to compare right and left side to highlight a prevalent pattern towards mandibular asymettry.

Methods: This is a descriptive cross sectional study in which pre-orthodontic treatment panoramic radiographs and lateral cephalograms of 224 patients (between 18 to 34 years) undergoing treatment in Orthodontic Department of Bahria University Medical and Dental College were used and traced on an acetate sheet. There were 74 patients in high angle,76 and 78 in low angle and normal angle group respectively based on their vertical growth pattern using SNMP angle. Condylar height (CH) and Ramal height (RH), and condylar plus ramal height (CH+RH) measurements were done as previously described by Habets.

Results: There was no statistically significant difference between the three groups as determined by one way ANOVA. Condylar height and Gonial angle showed statistically significant difference when right and left side was compared, with increased values on the right side.

Conclusion: There was no statistically significant difference in condylar, ramal, and total asymmetry index between different vertical groups. Between the right and left sides, condylar height and gonial angles were significantly increased on the right side. However, Ramal height showed no significant difference. Ramal index has a strong linear correlation with total asymmetry index.

doi: https://doi.org/10.12669/pjms.38.5.5294

How to cite this:Habib M, Ahsan T, Majeed O, Faheem F. Vertical growth pattern as a determinant of mandibular asymmetry. Pak J Med Sci. 2022;38(5):---------. doi: https://doi.org/10.12669/pjms.38.5.5294

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.
Assessment of frailty in cirrhosis using bedside measures and its correlation with Child-Turcotte-Pugh, MELD & MELD-Na Scores
Authors: Zuberi Bader Faiyaz , Rasheed Tazeen , Ali Faiza Sadaqat , Bader Nimrah , Sadaf Rabia
Published: April 2022

Objectives: To assess frailty in cirrhotic by calculating Liver Frailty Index (LFI) using bedside clinical tests and correlate it with Child-Turcotte-Pugh (CTP), MELD, MELD Na, Fib- 4 and Transient Elastography (TE) scores

Methods: This cross-sectional observational comparative study was carried out in Dr Ruth KM Pfau Civil Hospital, Karachi from August 2020 to September 2021. Patients were subjected to three performance-based testing including dominant hand grip strength (HGS), Chair to Stand (CTS) Time & Three Position Balance (TPB). LFI was calculated using the online LFI calculator, available at http://liverfrailtyindex.ucsf.edu and classified as ‘Robust’ if LFI <3.2, ‘Prefrail’ LFI between 3.2 and 4.4, and ‘Frail’ as LFI ≥4.5. Correlation of frailty with MELD, MELD-Na and CTP Scores was done. Means of MELD & MELD-Na Scores and CTP scores were calculated in all 3 classes of frailty using one way ANOVA. A p-value of ≤.05 was taken as significant.

Results: Out of 118 patients, 62 (52.5%) were males. Mean MELD score was 11.4 ±3.3, MELD-Na was 15.97 ±8.54, CTP 8.25 ±2.21, Fib-4 was 2.79 ±1.034 and TE score was 18.20 ±9.17. Mean LFI was 3.87 ±1.07; mean HGS was 18.12 ±4.68; mean of CTS was 9.62 ±3.55. LFI Class distribution in our cohort showed Robust were 36 (30.5%), Prefrail 34 (28.8%) and Frail were 48 (40.8%). Correlation of all these variables with LFI showed significant correlation with LFI, but highest correlation coefficient was seen with MELD-Na.

Conclusion: Significant correlation between frailty score in cirrhotic with cirrhosis severity scores highlights the need for frequently assessing LFI in all cirrhotic at regular follow up visits.

doi: https://doi.org/10.12669/pjms.38.5.5545

How to cite this:Zuberi BF, Rasheed T, Ali FS, Bader N, Sadaf R. Assessment of frailty in cirrhosis using bedside measures and its correlation with Child-Turcotte-Pugh, MELD & MELD-Na Scores. Pak J Med Sci. 2022;38(5):---------.  doi: https://doi.org/10.12669/pjms.38.5.5545

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.
Unmediated connection of mental health decline and suicide among medical and nonmedical undergraduates during the pandemic of COVID-19: A cross-sectional comparative study
Authors: Ansari Sadaf Konain , Khan Sadia Yasir , Jabeen Farkhanda , Riaz Areeba , Cheema Ali Hamza
Published: April 2022

Background and Objectives: All medicine and healthcare undergraduates were encountered with terminations and delays of professional examinations. These alterations were on topmost of other tasks the COVID-19 pandemic carried out for instance not roaming, covered faces with masks and specifically segregation. This interruption of normal life was a major cause of mental health disaster and it is no surprise that medicine and healthcare undergraduate has had high rates of psychological effects including hopelessness, stress and suicidal thoughts. This study aimed to investigate the unmediated connection of anxiety and stress related mental health decline and suicide among medical and nonmedical undergraduates during the pandemic of covid-19.

Methods: A multidiscipline online cross-sectional comparative study design was chosen for this study conducted from November 2020 to January 2021 with a pre-validated questionnaire to collect responses from sample size 1290. SPSS- 21 used for descriptive analysis of means, S.D, ANOVA and spearman’s correlations. Forward step-wise model of linear regression applies for true significant bivariate relationship (p<.001)

Results: The result shows that all three cohorts were affected. Among the non-medical cohorts, B-Pharmacy students had the high level (p<.001) of anxiety with suicide ideation response (n=200; 39.2%), along with lowest level of envisions care (19.5%; p<.001) in pandemic. Control and independent variable had a strong negative effects on B-Pharmacy and medical students with p<.000.

Conclusions: This study offered more data that the concerns, anxieties and uncertainties caused by pandemic COVID-19, don’t roll out alone but remain as long-lasting problems demanding ongoing attention.

doi: https://doi.org/10.12669/pjms.38.5.5686

How to cite this:Ansari SK, Khan SY, Jabeen F, Riaz A, Cheema AH. Unmediated connection of mental health decline and suicide among medical and nonmedical undergraduates during the pandemic of COVID-19: A cross-sectional comparative study. Pak J Med Sci. 2022;38(5):---------. doi: https://doi.org/10.12669/pjms.38.5.5686

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.