bluuebunny/crossref_metadata_2025 huggingface dataset:
The risk factors of neuropathic pain in neuromyelitis optica spectrum disorder: a retrospective case-cohort study
Authors: Li Xiaojun , Xu Haoyou , Zheng Zequan , Ouyang Huiying , Chen Guixian , Lou Zhenzhen , Chen Haoxuan , Zhang Jiahui , Zhan Yibo , Mao Hui , Zhang Changlin , Zhao Min , Zhao Yuanqi
Published: August 2022

Background

Neuropathic pain is a common complication in neuromyelitis optica spectrum disorder (NMOSD), which seriously affects the quality of life of NMOSD patients, with no satisfactory treatment. And risk factors of neuropathic pain are still uncertain.

Objective

To investigate the risk factors of neuropathic pain in a NMOSD cohort.

Materials and methods

Our study was a retrospective case-cohort study, the patients diagnosed with NMOSD in the Department of Neurology from the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2011 to October 2021 were screened. Inclusion criteria were: (1) patients diagnosed as NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria, (2) the aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) test was performed. Patients without AQP4-IgG antibody were excluded. Clinical data, including sex, age of the first onset, symptoms of the first episode including neuropathic pain and attack types, localization of lesions of the first episode on Magnetic Resonance Imaging (MRI), Extended disability status Scale (EDSS) of the first onset, treatment of immunosuppression in the first acute phase, disease modifying therapy (DMT), treatment of neuropathic pain and APQ4-IgG status were collected from the hospital system database. Neuropathic pain was defined according to the International Association for the Study of Pain criteria and was described as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system”.

Results

One hundred nineteen patients were screened and finally 86 patients fulfilling the inclusion and exclusion criteria were enrolled in our study. The prevalence of neuropathic pain in patients with NMOSD was 43.0%. Univariate analysis showed that the factors associated with neuropathic pain were the age at the onset, the attack type of optic neuritis, the attack type of myelitis, length of spinal cord involvement, localization of thoracic lesion, optic lesion, upper thoracic lesions, lower thoracic lesions, extended spinal cord lesions (≥ 3 spinal lesions), extended thoracic lesions (≥ 4 thoracic lesions), intravenous immunoglobulin and mycophenolate mofetil. Multivariate regression analysis showed that extended thoracic lesions (OR 20.21 [1.18–346.05], P = 0.038) and age (OR 1.35 (1–1.81) P = 0.050) were independently associated with neuropathic pain among NMOSD patients and that gender (OR 12.11 (0.97–151.64) P = 0.053) might be associated with neuropathic pain among NMOSD patients.

Conclusion

Extended thoracic lesions (≥ 4 thoracic lesions), age and gender might be independent risk factors of neuropathic pain among patients with NMOSD. However, with a small sample size and predominantly female, caution must be applied and these results need validating in further cohorts.
Apoptosis and autophagy markers predict survival in neoadjuvant treated oesophageal adenocarcinoma patients
Authors: El Mashed Shereen , O’Donovan Tracey R. , Kay Elaine , O’Grady Anthony , McManus Damian , Turkington Richard C. , McKenna Sharon L.
Published: August 2022

Background

Less than 20 % of patients with resectable oesophageal adenocarcinoma obtain a pathological response following neoadjuvant chemotherapy. Studies using oesophageal cancer cell lines have shown that drug sensitive tumour cells undergo apoptosis in response to drug treatment, whereas resistant cells induce autophagy and can recover following withdrawal of drug. In this study, we evaluated markers of apoptosis (active/cleaved caspase-3) and autophagy (LC3B) to establish whether these markers are useful prognostic indicators following neoadjuvant therapy.

Methods

Oesophageal adenocarcinoma tumour tissue from the Northern Ireland Biobank at Queens University Belfast was examined retrospectively. Tumours from 144 patients treated with platinum-based neoadjuvant chemotherapy followed by surgical resection were assembled into tissue microarrays prior to immunohistochemical analysis. Kaplan-Meier survival curves and log-rank tests were used to assess the impact of cleaved caspase-3 and LC3B expression on survival. Cox regression was used to examine association with clinical risk factors.

Results

High levels of cleaved caspase-3 were found in 14.6 % of patients and this correlated with a significantly better overall survival (p = 0.03). 38.9 % of patients had high cytoplasmic LC3B expression, which correlated with poor overall survival (p = 0.041). In addition, a distinct globular pattern of LC3B expression was identified in 40.3 % of patients and was also predictive of overall survival (p < 0.001). LC3B globular structures are also associated with tumour recurrence (p = 0.014).

When these markers were assessed in combination, it was found that patients who showed low/negative cleaved caspase-3 staining and high/positive staining for both patterns of LC3B had the worst overall survival (p < 0.001). Multi-variate analysis also indicated that this marker combination was an independent predictor of poor prognosis (p = 0.008; HR = 0.046, 95% CI = (0.005-0.443).

Conclusions

The expression of cleaved caspase-3 and specific LC3B staining patterns are associated with overall survival following neoadjuvant treatment. The combination of these markers is an independent indicator of outcome in neoadjuvant chemotherapy treated oesophageal adenocarcinoma.
Prevalence of depression and associated factors among people living with HIV/AIDS in public hospitals of Southeast Ethiopia
Authors: Desta Fikreab , Tasew Alelign , Tekalegn Yohannes , Zenbaba Demisu , Sahiledengle Biniyam , Assefa Tesfaye , Negash Wogene , Tahir Anwar , Regasa Tadele , Mamo Ayele , Teferu Zinash , Solomon Damtew , Gezahegn Habtamu , Bekele Kebebe , Regassa Zegeye , Atlaw Daniel
Published: August 2022

Background

Depression is the most frequent mental health condition among human immune deficiency virus or acquired immune deficiency syndrome (HIV/AIDS) patients. It has been related to negative health outcomes. This could lead to hospitalization and an increase in medical expenses. This study aimed to assess the prevalence of depression and associated factors among HIV/AIDS patients in public hospitals Bale Zone, Southeast Ethiopia.

Methods

A hospital-based cross-sectional study design was randomly employed among 554 study participants. A systematic random sampling technique was used to select the study subjects. A structured Patients Health Questionnaires- 9 was used to measure the depression status of HIV/AIDS patients. Data were collected using a pretested interviewer administered structured questionnaire as well as review of patients medical charts or records. Descriptive statistics were computed. Multivariable logistic regression analyses were conducted identify factors associated with the prevalence of depression. Adjusted odds ratio (AOR), along with a 95% confidence interval (CI), was used to estimate the strength of the association. A p-value of < 0.05 was considered statistically significant.

Results

The prevalence of depression among the study participants was found to be 44.9% (95% CI: 40.79%, 49.1%). Perceived HIV related stigma is the single most dominant predictor of depression [(AOR = 8.2, 95% CI: (4.96, 13.68)], low income level [(AOR = 3.1, 95% CI: (1.59, 6.22)] Experiencing any form of a side effect of highly active anti-retroviral therapy (HAART) [(AOR = 1.5, 95% CI: (1.04, 2.56)], having normal BMI [(AOR = 0.49, 95% CI: (0.29, 0.8)] being HIV patients at WHO clinical stage II [(AOR = 0.44, 95% CI: (0.22, 0.9)], were significantly associated with prevalence of depression.

Conclusion

The study revealed that the prevalence of depression among people living with HIV in the study settings was high, almost two out of every five HIV patients were depressed. Low income level, side effect to HAART, and having HIV related stigma were more likely to suffer from depression.
Poor sleep quality and associated factors among HIV-positive pregnant women in Northwest, Ethiopia: a facility-based, cross-sectional study
Authors: Legas Getasew , Beyene Getnet Mihretie , Asnakew Sintayehu , Belete Amsalu , Desie Tigabu
Published: August 2022

Background

Poor sleep quality during pregnancy might have an impact on adverse birth outcomes like premature rupture of membrane, preterm birth, lifelong neurocognitive impairment, low birth weight, and increased the risk of neonatal morbidity and mortality. In Ethiopia, the magnitude of poor sleep quality among this group of people is extremely limited. So, this study aims to determine the magnitude of poor sleep quality and its associated factors among HIV-positive pregnant women attending public hospitals in Northwest Ethiopia.

Methods

An institution-based cross-sectional study was done using a simple random sampling technique to recruit 411 HIV-positive pregnant women from January to March; 2021. Sleep quality over the last 1 month was measured using the Pittsburgh Sleep Quality Index (PSQI). General anxiety disorder (GAD-7), Sleep Hygiene Index (SHI), and List of Threatening of Experiences (LTE) instruments were used to identify factors associated with poor sleep quality. Bivariate and multivariable logistic regression with odds ratio and 95% CI were employed to identify determinant factors of poor sleep quality. Statistical significance association was declared at P-value < 0.05.

Results

A total of 411 out of 423 HIV-positive pregnant women were interviewed, with a response rate of 97.1%. The overall magnitude of poor sleep quality among HIV-positive pregnant was found to be 39.4% with a 95% of confidence interval (CI) (34.3, 44.3). Stressful life events, [AOR = 3.10, 95% CI (1.60, 6.01)], having comorbid general anxiety symptoms [AOR = 2.46, 95% CI (1.58, 3.81)], unplanned pregnancy [AOR = 2.18, 95% CI (1.20, 3.96)], and poor sleep hygiene practice [AOR = 2.23, 95% CI (1.21, 4.10)] were significantly associated with poor quality of sleep.

Conclusion

The overall magnitude of poor sleep quality among HIV-positive pregnant women was high. Stressful life events, poor sleep hygiene, unplanned pregnancy, and comorbid general anxiety symptoms were the determinant factors of poor sleep quality that should be taken high consideration for early detection and appropriate intervention for poor sleep quality in HIV-positive pregnant women.
Parents’ perceptions of school recess policies and practices
Authors: Ozenbaugh Isabella , Thalken Janelle , Logan Sam , Stellino Megan B. , Massey William V.
Published: August 2022

Background

Previous research has shown that school recess can provide children with physical, social and cognitive benefits; yet, recess opportunities and experiences may be different for different groups of children, specifically for children living in lower income environments, children of different racial groups other than white, and for children with disabilities. Parent perceptions of recess are important to consider as they serve as advocates for their children’s access and opportunities at school as well as an additional informant for children’s experiences at recess that may be useful for policymakers and school boards to consider.

Objective

To examine parent perceptions of recess by children’s disability status, children’s race and ethnicity, and family household income.

Method

Participants included 473 parents from the U.S.A. stratified across six household income levels. Data were collected through an online survey using Prolific in May of 2020]. Confirmatory factor analyses were run for measures assessing parents’ perception of belonging and victimization at recess, recess policies, and recess procedures. Regression analyses were run to examine if parents’ perception of recess were predicted by race, income, or child disability status.

Results

Results revealed that parents’ perceptions of recess were predicted by child disability status but not race or income. Specifically, parents’ perceptions were significantly predicted by child disability status regarding victimization (b = .13,SE = .06,p = .05), recess policies about withholding recess (b = .171,SE = .07,p = .01), and finally, student engagement at recess (b = .165,SE = .07,p = .02).

Conclusion

Results show that parents of children with a disability perceive a different recess experience for their child that involves more instances of victimization compared to parents of typically developing children. Based on these findings, school, district, and state policy makers could consider ensuring that recess includes multiple activities, is supervised by adults, and is a space where conflict resolution occurs, for creating a more inclusive environment for children with disabilities.
“To do, or not to do?”: determinants of stakeholders’ acceptance on dengue vaccine using PLS-SEM analysis in Malaysia
Authors: Arham Ahmad Firdhaus , Amin Latifah , Mustapa Muhammad Adzran Che , Mahadi Zurina , Yaacob Mashitoh , Arham Ahmad Fadhly , Norizan Nor Sabrena
Published: August 2022

Background

Dengue vaccine is a promising alternative for protecting communities from dengue. Nevertheless, public acceptance of the dengue vaccine must be considered before the authorities decide to carry out intensified research and recommend the vaccine adoption. This study aimed to assess the stakeholders' acceptability of the dengue vaccine and determine the factors that influence their intentions to adopt it.

Methods

Survey data collected from 399 respondents who represented two primary stakeholder groups: scientist (n = 202) and public (n = 197), were analysed using the partial least squares-structural equation modelling (PLS-SEM) technique.

Results

The findings revealed that the stakeholders claimed to have a highly positive attitude and intention to adopt the vaccine, perceived the vaccine as having high benefits, and displayed a high degree of religiosity and trust in the key players. The results also demonstrated that attitude and perceived benefits significantly influenced the intention to adopt the dengue vaccine. Furthermore, the perceived benefit was the most significant predictor of attitude to the dengue vaccine, followed by religiosity, attitudes to technology, and trust in key players.

Conclusion

The findings showed that the stakeholders in Malaysia were optimistic about the dengue vaccine with a positive attitude and perceived benefits as significant predictors of intention to adopt the vaccine. Hence, ongoing research can be intensified with the end target of recommending the vaccine for public adoption in hotspot areas. This finding contributes to the consumer behaviour literature while also providing helpful information to the government, policymakers, and public health officials about effective strategies for driving dengue vaccine acceptance in Malaysia and other countries with a history of severe dengue transmission.
Socioeconomic inequality in different phenotypes of childhood obesity and its determinants in Iran: a Blinder-Oaxaca decomposition method
Authors: Mahmoodi Zohreh , Gill Paramjit , Qorbani Mostafa , Mohammadian Khonsari Nami , Sheidaei Ali , Heshmat Ramin , Heidari-Beni Motahar , Kelishadi Roya
Published: August 2022

Background

Childhood obesity has become a significant public health issue worldwide. Socioeconomic status is among its key determinants. This study examined the socioeconomic inequality in different phenotypes of childhood obesity at the national level in Iran.

Methods

This national, multistage school cross-sectional study was undertaken in 2015 on 14,400 students aged 7–18 years from urban and rural areas of 30 provinces of Iran. Using principal component analysis, socioeconomic status (SES) was categorized into tertiles. SES inequality in different phenotypes of obesity (i.e., generalized obesity", "abdominal obesity", and combined obesity) was estimated using the concentration index. The determinants of this inequality were assessed by the Blinder-Oaxaca decomposition method.

Results

Overall, 14,274 students completed the study (response rate: 99%). The mean age was 12.28 years, 50.6% were boys, and 71.42% lived in urban areas. The prevalence of generalized obesity and abdominal obesity was 20.8% and 11.3%, respectively. The concentration index for different phenotypes of obesity was positive, indicating that inequality is more common amongst the low SES groups. High SES, being male, living in a rural, and having a positive family history of obesity were associated with general obesity. Moderate physical activity and living in a rural area were associated with abdominal obesity. In addition, living in a rural area, having a high SES, being male, and having a positive family history of obesity were associated with combined obesity.

Conclusion

According to the present study findings, all childhood obesity phenotypes were more prevalent in Iranian children with high SES. Therefore, due to obesity and other diseases, it is essential to implement environmental changes in addition to designing macro-educational programs and prevention strategies.
Evaluation of the synergistic impact of needle and forceps biopsy with electromagnetic navigation bronchoscopy: the CONFIDENT-ENB trial design
Authors: Kim Yeon Wook , Kim Hyung-Jun , Yoon Sung Hyun , Lee Kyung Hee , Park Young Mi , Ahn So Yeon , Song Myung Jin , Kwon Byoung Soo , Lim Sung Yoon , Lee Yeon Joo , Park Jong Sun , Cho Young-Jae , Yoon Ho Il , Lee Jae Ho , Lee Choon-Taek
Published: August 2022

Background

Electromagnetic navigation bronchoscopy (ENB) is an emerging advanced imaging-guided bronchoscopy technique for diagnosing peripheral lung lesions. However, the selection strategy for the optimal biopsy device and whether adopting a multi-tool strategy increases the diagnostic yield remains undetermined. The CONFIDENT-ENB trial (NCT05110131) is a prospective randomized study on ENB, performed in a least-invasive setting. The primary aim is to evaluate whether a combination of needle aspiration and forceps biopsy improves the diagnostic performance, and assess the comparative diagnostic value and discordance of the two devices.

Methods

The trial will recruit 142 participants with lung lesions suspected of malignancy who are eligible for an elective ENB procedure under moderate sedation. Participants will undergo ENB-guided needle aspiration and forceps biopsy in a randomized order without the use of any complementary techniques. All participants will be followed up subsequently for up to 12 months to conclude the final diagnosis of the biopsied lesions. Primary outcomes include the diagnostic yield and sensitivity of each biopsy modality and the diagnostic yield of the combined modalities.

Discussion

The CONFIDENT-ENB trial will prospectively evaluate the synergistic effectiveness and comparative accuracy of ENB-guided needle aspiration and forceps biopsy in a least-invasive setting. The results are expected to improve our understanding of the optimal tool-selection strategy for ENB.

Trial registration: ClinicalTrials.gov (NCT05110131). Prospectively registered on 5 November 2021.
Effects of osteoporosis on the biomechanics of various supplemental fixations co-applied with oblique lumbar interbody fusion (OLIF): a finite element analysis
Authors: Liu Zi-Xuan , Gao Zi-Wei , Chen Chao , Liu Zi-Yang , Cai Xin-Yi , Ren Ya-Nan , Sun Xun , Ma Xin-Long , Du Cheng-Fei , Yang Qiang
Published: August 2022

Background

Oblique lumbar interbody fusion (OLIF) is an important surgical modality for the treatment of degenerative lumbar spine disease. Various supplemental fixations can be co-applied with OLIF, increasing OLIF stability and reducing complications. However, it is unclear whether osteoporosis affects the success of supplemental fixations; therefore, this study analyzed the effects of osteoporosis on various supplemental fixations co-applied with OLIF.

Methods

We developed and validated an L3-S1 finite element (FE) model; we assigned different material properties to each component and established models of the osteoporotic and normal bone lumbar spine. We explored the outcomes of OLIF combined with each of five supplemental fixations: standalone OLIF; OLIF with lateral plate fixation (OLIF + LPF); OLIF with translaminar facet joint fixation and unilateral pedicle screw fixation (OLIF + TFJF + UPSF); OLIF with unilateral pedicle screw fixation (OLIF + UPSF); and OLIF with bilateral pedicle screw fixation (OLIF + BPSF). Under the various working conditions, we calculated the ranges of motion (ROMs) of the normal bone and osteoporosis models, the maximum Mises stresses of the fixation instruments (MMSFIs), and the average Mises stresses on cancellous bone (AMSCBs).

Results

Compared with the normal bone OLIF model, no demonstrable change in any segmental ROM was apparent. The MMSFIs increased in all five osteoporotic OLIF models. In the OLIF + TFJF + UPSF model, the MMSFIs increased sharply in forward flexion and extension. The stress changes of the OLIF + UPSF, OLIF + BPSF, and OLIF + TFJF + UPSF models were similar; all stresses trended upward. The AMSCBs decreased in all five osteoporotic OLIF models during flexion, extension, lateral bending, and axial rotation. The average stress change of cancellous bone was most obvious under extension. The AMSCBs of the five OLIF models decreased by 14%, 23.44%, 21.97%, 40.56%, and 22.44% respectively.

Conclusions

For some supplemental fixations, the AMSCBs were all reduced and the MMSFIs were all increased in the osteoporotic model, compared with the OLIF model of normal bone. Therefore, the biomechanical performance of an osteoporotic model may be inferior to the biomechanical performance of a normal model for the same fixation method; in some instances, it may increase the risks of fracture and internal fixation failure.
Lower rate of acceptable knee function in adolescents compared with young adults five years after acl reconstruction: results from the swedish national knee ligament register
Authors: Thorolfsson Baldur , Lundgren Michelle , Snaebjornsson Thorkell , Karlsson Jon , Samuelsson Kristian , Senorski Eric Hamrin
Published: August 2022

Background

The number of studies with a large cohort of patients that primarily focus on patient-reported outcomes after ACL reconstruction in children and adolescents is limited. The purpose of the present study was to determine whether patient age affects the proportion of patients that achieve a patient-acceptable symptom state (PASS) on the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales one, two, five and 10 years after an ACL reconstruction.

Methods

The patient data in the present study were extracted from the Swedish National Knee Ligament Register (SNKLR). Patients aged between five and 35 years that underwent a primary ACL reconstruction between 1 January 2005 and 31 December 2017 and had completed the KOOS questionnaire at the one-, two-, five- or 10-year follow-up were included. A total of 2,848 patients met the inclusion criteria and were included in the study; 47 paediatric patients (females 5–13, males 5–15 years), 522 adolescents (females 14–19, males 16–19 years) and 2,279 young adults (females 20–35, males 20–35 years). The results from the KOOS were presented as the mean and 95% confidence interval (CI) for the mean. For comparisons between groups, the chi-square test was used for non-ordered categorical variables. For pairwise comparisons between groups, Fisher’s exact test (2-sided) was used for dichotomous variables. All the statistical analyses was set at 5%.

Results

Adolescents reported a significantly lower score than young adults on the KOOS4 at the two- (68.4 vs. 72.1; P < 0.05), five- (69.8 vs. 76.0; P < 0.05) and 10-year follow-ups (69.8 vs. 78.2; P < 0.05). Moreover, a significantly smaller proportion of adolescents achieved a PASS on each of the KOOS subscales when compared with young adults at the five-year follow-up (Symptoms: 83.3% vs. 91.6%; Pain: 42.9% vs. 55.3%; Function in daily living: 31.4% vs. 41.1%; Function in sports and recreational activities: 42.3% vs. 55.7%; Knee-related quality of life: 50.0% vs. 65.0%; P < 0.05).

Conclusions

A significantly smaller proportion of adolescents achieved a PASS on each of the KOOS subscales when compared with young adults five years after ACL reconstruction. The results of the present study provide important information for physicians and physiotherapists treating young patients after an ACL injury and they can aid in providing realistic expectations in terms of the mid- and long-term outcomes.

Level of evidence

Prospective Observational Register/Cohort Study, Level II.
Awareness of human papillomavirus and acceptability of the vaccine among women in Palestine: is it time for policy adjustment?
Authors: Elshami Mohamedraed , Abukmail Hanan , Al-Slaibi Ibrahim , Alser Mohammed , Radaydeh Afnan , Alfuqaha Alaa , Thalji Mariam , Khader Salma , Khatib Lana , Fannoun Nour , Ahmad Bisan , Kassab Lina , Khrishi Hiba , Houssaini Deniz , Abed Nour , Nammari Aya , Abdallah Tumodir , Alqudwa Zaina , Idais Shahd , Tanbouz Ghaid , Hajajreh Ma’alem , Selmiyh Hala Abu , Abo-Hajouj Zakia , Hebi Haya , Zamel Manar , Skaik Refqa Najeeb , Hammoud Lama , Rjoub Saba , Ayesh Hadeel , Rjoub Toqa , Zakout Rawan , Alser Amany , Abu-El-Noor Nasser , Bottcher Bettina
Published: August 2022

Background

Progress has been made in the reduction of morbidity and mortality of cervical cancer by the implementation of human papillomavirus (HPV) vaccination programs. This study aimed to assess the awareness of Palestinian women about HPV as well as their knowledge and acceptability of the HPV vaccine and to examine the factors associated with good awareness.

Methods

This was a national cross-sectional study. Adult women were recruited from hospitals, primary healthcare centers, and public spaces in 11 Palestinian governorates using convenience sampling. A structured questionnaire was used for data collection. For each correctly answered question, one point was given. The total score was calculated and categorized into poor (0–10) and good awareness (11–21).

Results

The questionnaire was completed by 7223 women out of 8086 who were approached (response rate = 89.3%). A total of 7058 questionnaires were included in the final analysis; 4403 from the West Bank and Jerusalem (WBJ) and 2655 from the Gaza Strip. Women recruited from the Gaza Strip were younger, getting lower monthly incomes, and with fewer chronic diseases than women recruited from the WBJ.

Only 33 women (0.5%) displayed good awareness of HPV and its vaccine with 0.7% of women from WBJ and only 0.2% of women from the Gaza Strip. Completing post-secondary education, being employed or a student, and having a higher monthly income were associated with an increase in the likelihood of having good awareness.

Among women who had heard of HPV (n = 571, 8.1%), only 46 women (8.1%) reported familiarity with its vaccine. Women from the WBJ were more likely than women from the Gaza Strip to have heard about the HPV vaccine (0.9% vs. 0.2%). Most women agreed to receive the HPV vaccine themselves or for their daughters if it was given without cost or with a co-payment. No differences were found in the likelihood of agreeing to receive the HPV vaccine among women in the WBJ versus the Gaza Strip.

Conclusion

The overall awareness of HPV and its vaccine was extremely low. Inclusion of the HPV vaccine in the national immunization program could change this, especially as the HPV vaccine appeared to be acceptable.
Buoyancy and hydrostatic balance in a West Indian Ocean coelacanth Latimeria chalumnae
Authors: Lauridsen Henrik , Pedersen Jens Mikkel Hyllested , Ringgaard Steffen , Møller Peter Rask
Published: August 2022

Background

Buoyancy and balance are important parameters for slow-moving, low-metabolic, aquatic organisms. The extant coelacanths have among the lowest metabolic rates of any living vertebrate and can afford little energy to keep station. Previous observations on living coelacanths support the hypothesis that the coelacanth is neutrally buoyant and in close-to-perfect hydrostatic balance. However, precise measurements of buoyancy and balance at different depths have never been made. 

Results

Here we show, using non-invasive imaging, that buoyancy of the coelacanth closely matches its depth distribution. We found that the lipid-filled fatty organ is well suited to support neutral buoyancy, and due to a close-to-perfect hydrostatic balance, simple maneuvers of fins can cause a considerable shift in torque around the pitch axis allowing the coelacanth to assume different body orientations with little physical effort.

Conclusions

Our results demonstrate a close match between tissue composition, depth range and behavior, and our collection-based approach could be used to predict depth range of less well-studied coelacanth life stages as well as of deep sea fishes in general.
Rearrangement and domestication as drivers of Rosaceae mitogenome plasticity
Authors: Sun Manyi , Zhang Mingyue , Chen Xuening , Liu Yueyuan , Liu Binbin , Li Jiaming , Wang Runze , Zhao Kejiao , Wu Jun
Published: August 2022

Background

The mitochondrion is an important cellular component in plants and that functions in producing vital energy for the cell. However, the evolution and structure of mitochondrial genomes (mitogenomes) remain unclear in the Rosaceae family. In this study, we assembled 34 Rosaceae mitogenomes and characterized genome variation, rearrangement rate, and selection signal variation within these mitogenomes.

Results

Comparative analysis of six genera from the Amygdaloideae and five from the Rosoideae subfamilies of Rosaceae revealed that three protein-coding genes were absent from the mitogenomes of five Rosoideae genera. Positive correlations between genome size and repeat content were identified in 38 Rosaceae mitogenomes. Twenty repeats with high recombination frequency (> 50%) provided evidence for predominant substoichiometric conformation of the mitogenomes. Variations in rearrangement rates were identified between eleven genera, and within the Pyrus, Malus, Prunus, and Fragaria genera. Based on population data, phylogenetic inferences from Pyrus mitogenomes supported two distinct maternal lineages of Asian cultivated pears. A Pyrus-specific deletion (DEL-D) in selective sweeps was identified based on the assembled genomes and population data. After the DEL-D sequence fragments originally arose, they may have experienced a subsequent doubling event via homologous recombination and sequence transfer in the Amygdaloideae; afterwards, this variant sequence may have significantly expanded to cultivated groups, thereby improving adaptation during the domestication process.

Conclusions

This study characterizes the variations in gene content, genome size, rearrangement rate, and the impact of domestication in Rosaceae mitogenomes and provides insights into their structural variation patterns and phylogenetic relationships.
A novel CREBBP mutation and its phenotype in a case of Rubinstein–Taybi syndrome
Authors: Wang Qian , Wang Cong , Wei Wen Bin , Rong Wei Ning , Shi Xiang Yu
Published: August 2022

Background

This study was to report a novel CREBBP mutation and phenotype in a child with Rubinstein–Taybi syndrome.

Methods

Case report of a 9-year-old boy.

Results

We described the patient’s clinical manifestations in detail, and found that in addition to the typical systemic manifestations of the syndrome, the outstanding manifestation of the child was severe intellectual deficiency and prominent ocular abnormalities. Whole-exome sequencing and sanger sequencing were performed on the patient and his parents, a large intragenic deletion, covering the exon 1 region and part of the intron 1 region of the TRAP1 gene, and the entire region from intron 27 to exon 30 of the CREBBP gene (chr16:3745393-3783894) was identified on the patient. This mutation affected the CREBBP histone acetyltransferase (HAT) domain.

Conclusions

This findings in our patient add to the spectrum of genetic variants described in Rubinstein–Taybi syndrome and present a RSTS patient with various ocular anomalies including early onset glaucoma.
Anti-cancer therapeutic strategies based on HGF/MET, EpCAM, and tumor-stromal cross talk
Authors: Barzaman Khadijeh , Vafaei Rana , Samadi Mitra , Kazemi Mohammad Hossein , Hosseinzadeh Aysooda , Merikhian Parnaz , Moradi-Kalbolandi Shima , Eisavand Mohammad Reza , Dinvari Houra , Farahmand Leila
Published: August 2022

As an intelligent disease, tumors apply several pathways to evade the immune system. It can use alternative routes to bypass intracellular signaling pathways, such as nuclear factor-κB (NF-κB), Wnt, and mitogen-activated protein (MAP)/phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR). Therefore, these mechanisms lead to therapeutic resistance in cancer. Also, these pathways play important roles in the proliferation, survival, migration, and invasion of cells. In most cancers, these signaling pathways are overactivated, caused by mutation, overexpression, etc. Since numerous molecules share these signaling pathways, the identification of key molecules is crucial to achieve favorable consequences in cancer therapy. One of the key molecules is the mesenchymal-epithelial transition factor (MET; c-Met) and its ligand hepatocyte growth factor (HGF). Another molecule is the epithelial cell adhesion molecule (EpCAM), which its binding is hemophilic. Although both of them are involved in many physiologic processes (especially in embryonic stages), in some cancers, they are overexpressed on epithelial cells. Since they share intracellular pathways, targeting them simultaneously may inhibit substitute pathways that tumor uses to evade the immune system and resistant to therapeutic agents.
Longitudinal single-cell transcriptomics reveals distinct patterns of recurrence in acute myeloid leukemia
Authors: Zhai Yanan , Singh Prashant , Dolnik Anna , Brazda Peter , Atlasy Nader , del Gaudio Nunzio , Döhner Konstanze , Döhner Hartmut , Minucci Saverio , Martens Joost , Altucci Lucia , Megchelenbrink Wout , Bullinger Lars , Stunnenberg Hendrik G.
Published: August 2022

Background

Acute myeloid leukemia (AML) is a heterogeneous and aggressive blood cancer that results from diverse genetic aberrations in the hematopoietic stem or progenitor cells (HSPCs) leading to the expansion of blasts in the hematopoietic system. The heterogeneity and evolution of cancer blasts can render therapeutic interventions ineffective in a yet poorly understood patient-specific manner. In this study, we investigated the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs at genetic and transcriptional levels, and unveiled the underlying pathways and genes contributing to recurrence.

Methods

Whole-exome sequencing was used to detect somatic mutations and large copy number variations (CNVs). Single cell RNA-seq was performed to investigate the clonal heterogeneity between Dx-Re pairs and amongst patients.

Results

scRNA-seq analysis revealed extensive expression differences between patients and Dx-Re pairs, even for those with the same -presumed- initiating events. Transcriptional differences between and within patients are associated with clonal composition and evolution, with the most striking differences in patients that gained large-scale copy number variations at relapse. These differences appear to have significant molecular implications, exemplified by a DNMT3A/FLT3-ITD patient where the leukemia switched from an AP-1 regulated clone at Dx to a mTOR signaling driven clone at Re. The two distinct AML1-ETO pairs share genes related to hematopoietic stem cell maintenance and cell migration suggesting that the Re leukemic stem cell-like (LSC-like) cells evolved from the Dx cells.

Conclusions

In summary, the single cell RNA data underpinned the tumor heterogeneity not only amongst patient blasts with similar initiating mutations but also between each Dx-Re pair. Our results suggest alternatively and currently unappreciated and unexplored mechanisms leading to therapeutic resistance and AML recurrence.
Determining the feasibility for an overdose prevention line to support substance users who use alone
Authors: Ritchie Kim , Ghosh Sumantra Monty
Published: August 2022

Introduction

The majority of opioid-related deaths occur in suburban communities with people who use alone in their homes.

Background

To reach individuals who use substances alone, Grenfell Ministries, a not for profit agency in Hamilton Ontario created a phone-based supervision service to target individuals who use substances alone.

Methodology

Grenfell implemented a phone line service initially as a 3-month pilot eventually operationalized to a 24/7 phoneline to determine utilization of the service and test operational feasibility. Metrics such as timing of use, number of unique clients using the service and substances used were measured.

Results

The line was provincially utilized. Between February 1st and December 10, 2020, the line was used 64 times. Most calls occurred in the evening, with fentanyl being the most used substance. EMS was dispatched 3 times for overdoses, of which 2 individuals were successfully resuscitated, and one individual’s status being unknown.

Conclusion

The overdose prevention line can be implemented to support individuals who use alone. The service can successfully reduce risk of death from individuals who use alone and could be a valuable tool in addressing the opioid crisis. Further study needs to be conducted to determine its efficacy and safety in supporting clients who use alone.
Frailty and its association with health-related quality of life among older cancer patients: an evidence-based study from China
Authors: Su Mingzhu , Yao Nengliang , Shang Meimei , Shen Yuzhen , Qin Tingting , Wang Jialin , Sun Xiaojie
Published: August 2022

Background

There is limited information about the population characteristics and adverse health outcomes of older cancer patients in China. This study aimed to describe the prevalence of frailty and examine the association between frailty and health-related quality of life (HRQoL) among older cancer patients.

Methods

This was a cross-sectional study involving older patients diagnosed with cancer in two tertiary hospitals in Shandong Province, China. Frailty was assessed using Geriatric 8 (G-8). HRQoL was measured using the five-level EuroQol-5-dimension (EQ-5D-5L) questionnaire. The Tobit regression model and logistic regression model was used to identify the relationship between frailty and HRQoL.

Results

Of the 229 older patients, 175 (76.4%) were frail. Frail patients had lower EQ-5D-5L utility scores than those who were non-frail (0.830 vs. 0.889; P = 0.004). After adjustments for sociodemographic and cancer-related variables, frailty was statistically associated with worse health-related quality of life (OR = 6.024; P = 0.001).

Conclusion

Frailty was associated with deteriorated HRQoL in older patients with cancer. Early frailty screening and preventive interventions are essential for improving quality of life through decision-making or pretreatment optimization in geriatric oncology.
A novel inflammatory response-related signature predicts the prognosis of cutaneous melanoma and the effect of antitumor drugs
Authors: Xing Jiahua , Li Yan , Chen Youbai , Han Yan
Published: August 2022

Cutaneous melanoma (CM) is a skin cancer that is highly metastatic and aggressive, with a dismal prognosis. This is the first study to use inflammatory response-related genes to build a model and evaluate their predictive significance in CM. This study used public databases to download CM patients’ mRNA expression profiles and clinical data to create multigene prognostic markers in the UCSC cohort. We compared overall survival (OS) between high- and low-risk groups using the Kaplan-Meier curve and determined independent predictors using Cox analysis. We also used enrichment analysis to assess immune cell infiltration fraction and immune pathway-related activity using KEGG enrichment analysis. Furthermore, we detected prognostic genes’ mRNA and protein expression in CM and normal skin tissues using qRT-PCR and immunohistochemistry. Finally, we developed a 5-gene predictive model that showed that patients in the high-risk group had a considerably shorter OS than those in the low-risk group. The analysis of the receiver operating characteristic (ROC) curve proved the model’s predictive ability. We also conducted a drug sensitivity analysis and discovered that the expression levels of prognostic genes were substantially linked with cancer cell sensitivity to antitumor medicines. The findings show that the model we developed, which consists of five inflammatory response-related genes, can be used to forecast the prognosis and immunological state of CM, giving personalized and precision medicine a new goal and direction.
Effect of Notch1 signaling on cellular proliferation and apoptosis in human laryngeal carcinoma
Authors: Li Dawei , Xu Dan , Zhang Yifei , Chen Penghui , Xie Jin
Published: August 2022

Background

The occurrence and development of malignancies include excessive proliferation and apoptosis resistance in tumor cells. This study aimed to identify the effects of Notch1 signaling on proliferation and apoptosis of laryngeal cancer cells in a hypoxic microenvironment.

Methods

Notch1 and Ki-67 expression in laryngeal squamous cell carcinoma (LSCC) tissues was detected by immunohistochemistry. The apoptotic index (AI) of LSCC was evaluated by the TUNEL method. Small interfering RNA (siRNA) was used to inhibit Notch1 expression in laryngeal cancer cells. Real-time PCR was used to measure Notch1, Hes1, and Hey1 mRNA expression, and Western blotting was used to measure Notch1 and Notch1 intracellular domain (N1ICD) protein expression. Annexin V-FITC/propidium iodide staining and Cell Counting Kit-8 assays were used to measure cell apoptosis and proliferation, respectively.

Results

Notch1 expression was significantly related to the proliferation index (PI) and AI in LSCC tissues. Hypoxia could induce proliferation and inhibit apoptosis in cancer cells. Notch1 expression and Notch1 signaling activity could be upregulated by hypoxia. Suppressing Notch1 signaling activity in hypoxic cells could decrease proliferation and increase apoptosis.

Conclusions

Our study has demonstrated that hypoxia may promote proliferation and inhibit apoptosis of laryngeal cancer cells. Notch1 signaling may play a pivotal role in regulating the proliferation and apoptosis resistance of laryngeal cancer cells under hypoxic conditions.
hUCMSCs reduce theca interstitial cells apoptosis and restore ovarian function in premature ovarian insufficiency rats through regulating NR4A1-mediated mitochondrial mechanisms
Authors: Luo Qianqian , Tang Yu , Jiang Zhonglin , Bao Hongchu , Fu Qiang , Zhang Hongqin
Published: August 2022

Background

Human umbilical cord mesenchymal stem cells (hUCMSCs, retrospectively registered) have a lot of promise for treating theca interstitial cells(TICs) dysfunction in premature ovarian insufficiency (POI). The mechanisms, however, are still unknown.

Methods

To examine the therapeutic and find the cause, we used both in vivo cisplatin-induced POI rat model and in vitro TICs model. HUCMSCs were injected into the tail veins of POI rats in an in vivo investigation. Then, using ELISA, HE staining, TUNEL apoptosis test kit, immunohistochemistry and western blot, researchers examined hormonal levels, ovarian morphology, TICs apoptosis, NR4A1 and Cyp17a1 in response to cisplatin treatment and hUCMSCs. TICs were obtained from the ovaries of rats and treated with the cisplatin, hUCMSCs supernatant, and the antagonist of NR4A1——DIM-C-pPhOH. ELISA, immunofluorescence, flow cytometry, JC-1 labeling and western blot analysis were used to detect T levels, Cyp17a1, NR4A1, and the anti-apoptotic protein Bcl-2, as well as pro-apoptotic proteins Bax, caspase-9, caspase-3, and cytochrome C(cytc).

Results

We discovered that hUCMSCs restored the ovarian function, particularly TICs function based on measures of Cyp17a1 and T expression. NR4A1 was found in ovarian TICs of each group and NR4A1 expression was lower in the POI rats but higher following hUCMSCs therapy. The apoptosis of TICs generated by cisplatin was reduced after treatment with hUCMSCs. In vitro, NR4A1 was expressed in the nucleus of TICs, and NR4A1 as well as phospho-NR4A1 were decreased, following the apoptosis of TICs was emerged after cisplatin treatment. Interestingly, the localization of NR4A1 was translocated from the nucleus to the cytoplasm due to cisplatin. HUCMSCs were able to boost NR4A1 and phospho-NR4A1 expression while TICs’ apoptosis and JC-1 polymorimonomor fluorescence ratios reduced. Furthermore, Bcl-2 expression dropped following cisplatin treatment, whereas Bax, cytc, caspase-9, and caspase-3 expression rose; however, hUCMSCs treatment reduced their expression. In addition, DIM-C-pPhOH had no effect on the NR4A1 expression, but it did increase the expression of apoptosis-related factors such as Bax, cytc, caspase-9, and caspase-3, causing the apoptosis of TICs.

Conclusions

These data show that hUCMSCs therapy improves ovarian function in POI rats by inhibiting TICs apoptosis through regulating NR4A1 -mediated mitochondrial mechanisms.
Concentrations of oocyte secreted GDF9 and BMP15 decrease with MII transition during human IVM
Authors: Cadenas Jesús , Pors Susanne Elisabeth , Kumar Ajay , Kalra Bhanu , Kristensen Stine Gry , Andersen Claus Yding , Mamsen Linn Salto
Published: August 2022

Background

The suggested effects of the oocyte secreted GDF9 and BMP15 growth factors on oocyte maturation are currently based on recombinant proteins, and little is known about native GDF9 and BMP15 in humans.

Methods

Human immature cumulus-oocyte complexes (COCs) obtained in connection with ovarian tissue cryopreservation (OTC) underwent in vitro maturation (IVM). Oocyte-produced GDF9 and BMP15 were detected in COCs using immunofluorescence, and in fresh GV oocytes and in GV and MII oocytes after IVM by western blot. Concentrations of GDF9, BMP15 homodimers, and GDF9/BMP15 heterodimer in spent media after IVM were measured by ELISA. The relative expression of seven genes from the GDF9 and BMP15 signaling pathways (BMPR2, ALK5, ALK6, SMAD1, SMAD2, SMAD3, and SMAD5) was evaluated in fresh cumulus cells (before IVM) and in cumulus cells from GV and MII oocytes after IVM by RT-qPCR.

Results

We detected native pro-mature GDF9 and BMP15 in human oocytes with molecular weights (Mw) of 47 kDa and 43 kDa, respectively. Concentrations of GDF9 and BMP15 in spent media after IVM were detected in 99% and 64% of the samples, respectively. The GDF9/BMP15 heterodimer was detected in 76% of the samples. Overall, the concentration of GDF9 was approximately 10-times higher than BMP15. The concentrations of both GDF9 and BMP15 were significantly lower in spent medium from MII oocytes than in media from oocytes that remained at the GV stage. Concentrations of the GDF9/BMP15 heterodimer did not differ between GV and MII oocytes. Furthermore, BMPR2, SMAD3, and SMAD5 were significantly upregulated in cumulus cells from MII oocytes, indicating that both GDF9 and BMP15 signaling were active during oocyte meiotic resumption in vitro.

Conclusion

These data suggest that the driving mechanisms for oocyte nuclear maturation may involve both GDF9 and BMP15 homodimers, while the role of the GDF9/BMP15 heterodimer is questionable.