bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival outcomes of children with relapsed or refractory myeloid leukemia associated with Down syndrome
Authors: Raghuram Nikhil , Hasegawa Daisuke , Nakashima Kentaro , Rahman Syaza , Antoniou Evangelia , Skajaa Torjus , Merli Pietro , Verma Anupam , Rabin Karen R. , Aftandilian Catherine , Kotecha Rishi S. , Cheuk Daniel , Jahnukainen Kirsi , Kolenova Alexandra , Balwierz Walentyna , Norton Alice , O’Brien Maureen , Cellot Sonia , Chopek Ashley , Arad-Cohen Nira , Goemans Bianca , Rojas-Vasquez Marta , Ariffin Hany , Bartram Jack , Kolb E. Anders , Locatelli Franco , Klusmann Jan-Henning , Hasle Henrik , McGuire Bryan , Hasnain Afia , Sung Lillian , Hitzler Johann
Published: February 2023

Children with Down syndrome (DS) are at a significantly higher risk of developing acute myeloid leukemia, also termed myeloid leukemia associated with DS (ML-DS). In contrast to the highly favorable prognosis of primary ML-DS, the limited data that are available for children who relapse or who have refractory ML-DS (r/r ML-DS) suggest a dismal prognosis. There are few clinical trials and no standardized treatment approach for this population. We conducted a retrospective analysis of international study groups and pediatric oncology centers and identified 62 patients who received treatment with curative intent for r/r ML-DS between year 2000 to 2021. Median time from diagnosis to relapse was 6.8 (range, 1.1-45.5) months. Three-year event-free survival (EFS) and overall survival (OS) were 20.9 ± 5.3% and 22.1 ± 5.4%, respectively. Survival was associated with receipt of hematopoietic stem cell transplantation (HSCT) (hazard ratio [HR], 0.28), duration of first complete remission (CR1) (HR, 0.31 for > 12 months) and attainment of remission after relapse (HR, 4.03). Patients who achieved complete remission (CR) before HSCT, had an improved OS and EFS of 56.0 ± 11.8% and 50.5 ± 11.9%, respectively compared to those who underwent HSCT without CR (3-year OS and EFS of 10.0 ± 9.5%). Treatment failure after HSCT was predominantly because of disease recurrence (52%) followed by treatment-related mortality (10%). The prognosis of r/r ML-DS remains dismal even in the current treatment period and serve as a reference point for current prognostication and future interventional studies. Clinical trials aimed at improving the survival of patients with r/r ML-DS are needed.
NRXN1 depletion in the medial prefrontal cortex induces anxiety-like behaviors and abnormal social phenotypes along with impaired neurite outgrowth in rat
Authors: Wu Di , Zhu Jiansheng , You Lianghui , Wang Jingyu , Zhang Sufen , Liu Zhonghui , Xu Qu , Yuan Xiaojie , Yang Lei , Wang Wei , Tong Meiling , Hong Qin , Chi Xia
Published: February 2023

Background

Neurodevelopmental disorders (NDDs) are a group of disorders induced by abnormal brain developmental processes. The prefrontal cortex (PFC) plays an essential role in executive function, and its role in NDDs has been reported. NDDs are associated with high-risk gene mutations and share partially overlapping genetic abnormalities.

Methods

Neurexins (NRXNs) are related to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). NRXN1, an essential susceptibility gene for NDDs, has been reported to be associated with NDDs. However, little is known about its key role in NDDs.

Results

NRXN1 downregulation in the medial PFC induced anxiety-like behaviors and abnormal social phenotypes with impaired neurite outgrowth in Sh-NRXN1 in prefrontal neurons. Moreover, tandem mass tag (TMT)-based proteomic analysis of rat brain samples showed that NRXN1 downregulation led to significant proteome alterations, including pathways related to the extracellular matrix, cell membrane, and morphologic change. Furthermore, full-automatic immunoblotting analysis verified the differently expressed proteins related to cell morphology and membrane structure.

Conclusions

Our results confirmed the association of NRXN1 with abnormal behaviors in NDDs and provided richer insights into specific prefrontal knockdown in adolescence, potentially expanding the NRXN1 interactome and contributing to human health.

Graphical abstract
Auxin efflux carrier ZmPIN1a modulates auxin reallocation involved in nitrate-mediated root formation
Authors: Wang Yubin , Xing Jiapeng , Wan Jiachi , Yao Qingqing , Zhang Yushi , Mi Guohua , Chen Limei , Li Zhaohu , Zhang Mingcai
Published: February 2023

Background

Auxin plays a crucial role in nitrate (NO3–)-mediated root architecture, and it is still unclear that if NO3– supply modulates auxin reallocation for regulating root formation in maize (Zea mays L.). This study was conducted to investigate the role of auxin efflux carrier ZmPIN1a in the root formation in response to NO3– supply.

Results

Low NO3– (LN) promoted primary root (PR) elongation, while repressed the development of lateral root primordia (LRP) and total root length. LN modulated auxin levels and polar transport and regulated the expression of auxin-responsive and -signaling genes in roots. Moreover, LN up-regulated the expression level of ZmPIN1a, and overexpression of ZmPIN1a enhanced IAA efflux and accumulation in PR tip, while repressed IAA accumulation in LRP initiation zone, which consequently induced LN-mediated PR elongation and LR inhibition. The inhibition rate of PR length, LRP density and number of ZmPIN1a-OE plants was higher than that of wild-type plants after auxin transport inhibitor NPA treatment under NN and LN conditions, and the degree of inhibition of root growth in ZmPIN1a-OE plants was more obvious under LN condition.

Conclusion

These findings suggest that ZmPIN1a was involved in modulating auxin levels and transport to alter NO3–-mediated root formation in maize.
Lung nodule pre-diagnosis and insertion path planning for chest CT images
Authors: Xie Rong-Li , Wang Yao , Zhao Yan-Na , Zhang Jun , Chen Guang-Biao , Fei Jian , Fu Zhuang
Published: February 2023

Medical image processing has proven to be effective and feasible for assisting oncologists in diagnosing lung, thyroid, and other cancers, especially at early stage. However, there is no reliable method for the recognition, screening, classification, and detection of nodules, and even deep learning-based methods have limitations. In this study, we mainly explored the automatic pre-diagnosis of lung nodules with the aim of accurately identifying nodules in chest CT images, regardless of the benign and malignant nodules, and the insertion path planning of suspected malignant nodules, used for further diagnosis by robotic-based biopsy puncture. The overall process included lung parenchyma segmentation, classification and pre-diagnosis, 3-D reconstruction and path planning, and experimental verification. First, accurate lung parenchyma segmentation in chest CT images was achieved using digital image processing technologies, such as adaptive gray threshold, connected area labeling, and mathematical morphological boundary repair. Multi-feature weight assignment was then adopted to establish a multi-level classification criterion to complete the classification and pre-diagnosis of pulmonary nodules. Next, 3-D reconstruction of lung regions was performed using voxelization, and on its basis, a feasible local optimal insertion path with an insertion point could be found by avoiding sternums and/or key tissues in terms of the needle-inserting path. Finally, CT images of 900 patients from Lung Image Database Consortium and Image Database Resource Initiative were chosen to verify the validity of pulmonary nodule diagnosis. Our previously designed surgical robotic system and a custom thoracic model were used to validate the effectiveness of the insertion path. This work can not only assist doctors in completing the pre-diagnosis of pulmonary nodules but also provide a reference for clinical biopsy puncture of suspected malignant nodules considered by doctors.
Pharmacological and non-pharmacological interventions in management of peripheral venipuncture-related pain: a randomized clinical trial
Authors: Yu Zhuowen , Zhou Yiwen , Xu Xiaofeng , Lin Lili , Le Qian , Gu Ying
Published: February 2023

Background

Venipuncture is a routine nursing procedure in the pediatric ward for blood collection and transfusion. However, this procedure can cause severe pain and distress if not adequately managed.

Methods

Children aged 3–16 years old were randomized into three groups: EMLA group, distraction group, and combined group. The primary outcome was children’s self-reported pain scored using the Wong-Baker FACES® Pain Rating Scale. The parents-reported and observer-reported pain were scored using the Revised Face, Legs, Activity, Cry and Consolability Scale, and children’s salivary cortisol levels, heart rate, percutaneous oxygen saturation, venipuncture duration and retaining time of IV cannulas were the secondary outcomes.

Results

A total of 299 children (167 male, 55.8%, median age 8.5) were enrolled: EMLA group (n = 103), distraction group(n = 96) and combined group(n = 100). There was no statistical difference in self-reported pain (P = 0.051), parent-reported pain (P = 0.072), and observer-reported pain (P = 0.906) among the three groups. All three interventions can decrease children’s pain during IV cannulations. Additionally, the distraction group's salivary cortisol levels were lower than the combined group(P = 0.013). Furthermore, no significant difference was observed in the heart rate(P = 0.844), percutaneous oxygen saturation (P = 0.438), venipuncture duration (p = 0.440) and retaining time of IV cannulas (p = 0.843) among the three groups.

Conclusions

All three groups responded with slight pain during the peripheral venipuncture procedure. Therefore, medical workers in pediatric settings can use the interventions appropriate for their medical resources and availability while involving parents and children’s preferences whenever possible.

Trial registration

This trial was registered onhttps://register.clinicaltrials.gov/(Gov.ID NCT04275336).
Clinical outcomes of pediatric osteomyelitis
Authors: Disch Kylie , Hill Deirdre A. , Snow Harry , Dehority Walter
Published: February 2023

Background

Osteomyelitis in children may produce severe sequelae. However, the frequency and distribution of such complications by type of osteomyelitis (chronic or acute) is not well described.

Methods

We searched the HealthFacts® database (containing medical information on 68 million individual patients in the United States) with 238 International Classification of Diseases (ICD) version 10 codes for acute osteomyelitis and chronic osteomyelitis appearing in 2015. Outcomes were recorded for each subject, including development of limb length discrepancies, pathologic fractures, mortality, and need for multiple surgeries or prolonged orthopedic care (one to two years following diagnosis). Gender, age and season of diagnosis were also assessed. Chi-square tests were used to compare differences between categorical variables, and t-tests between continuous variables.

Results

Eight hundred sixty-nine subjects were included (57.4% male). Children with chronic osteomyelitis were older than those with acute osteomyelitis (median 9.5 years vs 12.0, respectively, p = .0004). Diagnoses were more common in winter (p = .0003). Four subjects died while hospitalized during the study period (two with acute osteomyelitis, two with chronic osteomyelitis). Limb length discrepancies were rare and similarly distributed between infection types (≤ 1.3% of subjects, p = .83). Subjects with chronic osteomyeltis were more likely to require long-term orthopedic follow-up (14.0% vs. 4.8% for acute osteomyelitis, p < .0001), suffer from pathologic fractures (1.5% vs < 1.0%, p = .003) and to require multiple surgeries (46.0% vs. 29.3%, p = .04).

Conclusions

Though infrequent, serious outcomes from osteomyelitis are more common with chronic osteomyelitis than acute osteomyelitis.
The genotypic and phenotypic characteristics contributing to high virulence and antibiotics resistance in Escherichia coli O25-B2-ST131 in comparison to non- O25-B2-ST131
Authors: Shahbazi Razieh , Salmanzadeh-Ahrabi Siavosh , Aslani Mohammad Mehdi , Alebouyeh Masoud , Falahi Jamal , Nikbin Vajihe Sadat
Published: February 2023

Background

Escherichia coli serogroup O25b-sequence type 131 (E. coli O25-B2-ST131) is considered as multidrug-resistant and hypervirulent organism. There is lack of data about involvement of this pathogen in the children’s infection. In this study, the prevalence, and clonality, virulence capacity, and antibiotic resistance phenotype and genotype of E. coli O25-B2-ST131 compared with non-O25-B2-ST131 isolates were investigated in children with urinary tract infection in Tehran, Iran.

Methods

The E. coli isolates from urine samples were identified using conventional microbiological methods. Characterization of E. coli O25-B2-ST131 clone, antibiotic susceptibility, biofilm formation, ESBLs phenotype and genotype, serum resistance, hemolysis, hydrophobicity, and formation of curli fimbriae were done using conventional microbiological and molecular methods. Clonality of the isolates was done by rep-PCR typing.

Results

Among 120 E. coli isolates, the highest and lowest antibiotic resistance was detected against ampicillin (92, 76.6%) and imipenem 5, (4.1%), respectively. Sixty-eight (56.6%) isolates were ESBL-producing and 58 (48.3%) isolates were considered as multi-drug resistance (MDR). The prevalence of ESBL-producing and MDR isolates in O25-B2-ST131 strains was higher compared with the non-O25-B2-ST131 strains (p value < 0.05). O25-B2-ST131 strains showed significant correlation with serum resistance and biofilm formation. Amongst the resistance and virulence genes, the prevalence of iucD, kpsMTII, cnf1, vat, blaCTX-M-15, and blaSHV were significantly higher among O25-B2-ST131 isolates in comparison with non-O25-B2-ST131 isolates (p value < 0.05). Considering a ≥ 80% homology cut-off, fifteen different clusters of the isolates were shown with the same rep-PCR pattern.

Conclusions

Our results confirmed the involvement of MDR-ESBLs producing E. coli strain O25-B2-ST131 in the occurrence of UTIs among children. Source tracking and control measures seem to be necessary for containment of the spread of hypervirulent and resistance variants in children.
Relationships between training load, peak height velocity, muscle soreness and fatigue status in elite-level young soccer players: a competition season study
Authors: Nobari Hadi , Eken Özgür , Kamiş Okan , Oliveira Rafael , González Pablo Prieto , Aquino Rodrigo
Published: February 2023

Background

This study aimed to compare training load parameters, delayed onset muscle soreness (DOMS), and fatigue status between season periods (1st and 2nd halves) in U14 soccer players and to analyze the relationships between training load parameters based on season periods (1st and 2nd halves) with peak height velocity (PHV), DOMS, and fatigue status in under-14 (U14) young elite soccer players. Additionally, it was intended to analyze if fatigue, DOMS and PHV could explain training load parameters across the season.

Methods

Twenty U14 players that competed in the national league participated in this study. The players were monitored during the whole season (26 weeks), and evaluations were carried out at the end of the in-season. Anthropometric and body composition parameters and the maturity offset of each player were utilized to compute each player's age at PHV. Players reported their levels of DOMS and fatigue status using Hooper index questionnaires. The internal load was monitored using the rating of perceived exertion (RPE). Acute weekly internal load (AW), chronic weekly internal load (CW), acute: chronic workload ratio (ACWR), training monotony (TM), and training strain (TS) were also obtained.

Results

The main results showed that TM was higher in the 2nd half, while CW, AW and DOMS were higher in the 1st half of the season. Moreover, the main correlations showed a positive correlation between PHV and TS (2nd half of the season) and between fatigue and TM (1st half of the season).

Conclusion

In conclusion, variations in well-being status and PHV cannot explain the variations in internal training loads in elite U14 soccer players. In addition, internal training load indices during the first half of the competitive season can promote a fundamental base for progression loads during the second period of the competitive season.
Cognitive behavior therapy for diabetes distress, depression, health anxiety, quality of life and treatment adherence among patients with type-II diabetes mellitus: a randomized control trial
Authors: Abbas Qasir , Latif Sana , Ayaz Habib Hina , Shahzad Salman , Sarwar Uzma , Shahzadi Mafia , Ramzan Zoobia , Washdev Washdev
Published: February 2023

Objective

Diabetes distress typically causes depressive symptoms; common comorbidity of diabetes unpleasantly affects patients’ medical and psychological functions. Psychotherapeutic interventions are effective treatments to treat depressive symptoms and to improve the quality of life in many chronic diseases including diabetes. The present study investigated the efficacy of cognitive behavior therapy (CBT) to treat depressive symptoms in patients with type 2 diabetes mellitus (T2DM) using experimental and waitlist control conditions.

Materials and Methods

A total of 130 diagnosed patients with T2DM were taken from outdoor patients services of different hospitals in Faisalabad. Ninety patients met the eligibility criteria and were randomly assigned to experimental (n = 45) and waitlist control (n = 45) conditions. All the patients completed clinical interviews and assessment measures at pre-and post-assessment stages (16 weeks intervals). Medical consultants at the respective hospitals diagnosed the patients on the base of their medical reports and then referred those patients to us. Then we used different scales to assess primary and secondary outcomes: Diabetes Distress Scale (DDS) and Patient Health Questionnaire (PHQ) to assess primary outcomes, and a Short Health Anxiety Inventory (SHAI), a Revised Version of the Diabetes Quality of Life Questionnaire (DQLQ), and a General Medication Adherence Scale (GMAS) were used to investigate secondary outcomes. Repeated measure ANOVA was used to analyze the results.

Results

The findings indicated that patients who received CBT got a significant reduction in their diabetes distress F(1,60) = 222.710,P < 0.001, η2 = .788), depressive symptoms F(1,60) = 94.436,P < 0.001, η2 = .611), health anxiety F(1,60) = 201.915,P < .0.001, η2 = 771), and a significant improvement in their quality of life F(1,60) = 83.352,P < 0.001, η2 = .581), treatment adherence F(1,60) = 67.579,P < 0.001, η2 = .566) and physical activity schedule F(1,60) = 164.245, P < .0.001, η2 = .736 as compared to the patients in waitlist control condition.

Conclusion

It is concluded that cognitive behavior therapy is an effective and promising intervention for depressive symptoms, diabetes distress, and health anxiety which also helps the person to promote quality of life, treatment adherence and physical activity.
Tinospora sinensis (Lour.) Merr alkaloid rich extract induces colon cancer cell death via ROS mediated, mTOR dependent apoptosis pathway: “an in-vitro study”
Authors: Badavenkatappa gari Sreelakshmi , Nelson Vinod K. , Peraman Ramalingam
Published: February 2023

Background

Colorectal cancer (CRC) is the second most mortality rate causing disease after lung cancer. Though there is a significant improvement in the treatment schedule offered to CRC. However, there is no notable decrease in terms of cases as well as death rate. Hence, there is an urgent need to discover novel cancer therapeutics to treat CRC. Since ancient times, the use of phytochemicals has drawn huge attention as chemo-preventive and chemotherapeutic agents. Earlier studies on Tinospora sinensis (TS) revealed the cytotoxic effect on human colorectal carcinoma (HCT-116) cells, yet the mechanism is to be uncovered. Therefore, the present study was designed to study the cell death mechanism of TS in HCT-116 cells.

Method

Different extracts such as n-hexane, ethyl acetate, and ethanol extracts from the root part of TS were prepared using a cold maceration process. The extracts were screened against cancer cell lines by methyl thiazoldiphenyltetrazolium bromide (MTT) assay. From the result, the most active extract was subjected to gas chromatography-mass spectrometry (GC-MS) and Fourier-Transform infrared spectroscopy (FTIR) analyses to identify the major constituents. Finally, the mechanism of cytotoxicity to cancer cells for the most active extract was evaluated using various experiments such as cell cycle analysis, Annexin-V assay, and Western blot.

Results

The results from the MTT assay indicated that the n-hexane extract of TS inhibits the growth of HCT-116 cells more effectively than other cancer cells like Henrietta Lacks cervical cancer cells (Hela), and Michigan cancer foundation-breast cancer (MCF-7). The GC-MS and FT-IR analyses revealed the presence of alkaloids in the n-hexane extract and were responsible for the apoptosis activity in HCT-cells via reactive oxygen species (ROS) generation, and phosphoinositide 3-kinase (PI3K)/ protein Kinase B (Akt)/ mammalian target of rapamycin (mTOR) down-regulation.

Conclusion

This study concludes that this finding is unique of its kind, and for the first time. The anticancer effect of TS root is specific to colon cancer cells (HCT-116). This distinctive finding helps the researchers to investigate further, and to identify a novel source for anti-colon cancer drug candidates in near future.
The mediating effect of critical thinking between interest in learning and caring among nursing students: a cross-sectional study
Authors: Tong Lai Kun , Au Mio Leng , Li Yue Yi , Ng Wai I. , Wang Si Chen
Published: February 2023

Background

Previous studies have explored the influence of interest in learning on caring and critical thinking, as well as the relationship between caring and critical thinking. However, the mediating effect of critical thinking in interest learning and caring among nursing students has not been clarified.

Methods

Nursing students who enrolled for the 2021/2022 academic year in diploma, undergraduate, or graduate programs in five provinces of China (Guangdong, Sichuan, Jiangsu, Hunan and Macao). An online survey with a convenience sampling method was employed to collect data. The questionnaires were administered to 692 participants between January 20 and 26, 2022. Amos 26.0 was employed to establish the structural equation modelling and analyze the mediating effect of critical thinking on interest in learning and caring.

Results

The first regression equation showed that interest in learning significantly influenced caring (β = 0.339, p <  0.001). The third regression equation showed that critical thinking significantly influenced caring (β = 0.494, p <  0.001). The effect of interest in learning on caring was less in the third equation than in the first equation (β = 0.154 vs β = 0.339), which indicates partial mediation. Furthermore, interest in learning had an indirect positive effect (β = 0.186, p <  0.001) on caring mediated by critical thinking, with 95% confidence interval of 0.142 to 0.233.

Conclusions

Critical thinking was a significant mediator of the relationship between interest in learning and caring. It is suggested that nursing colleges and instructors should take into account students’ interest in learning and critical thinking as potential intervention elements to enhance caring.
The effect of distance to health facility on neonatal mortality in Ethiopia
Authors: Kibret Getiye Dejenu , Demant Daniel , Hayen Andrew
Published: February 2023

Introduction

In Ethiopia, more than half of newborn babies do not have access to Emergency Obstetric and Neonatal Care (EmONC) services. Understanding the effect of distance to health facilities on service use and neonatal survival is crucial to recommend policymakers and improving resource distribution. We aimed to investigate the effect of distance to health services on maternal service use and neonatal mortality.

Methods

We implemented a data integration method based on geographic coordinates. We calculated straight-line (Euclidean) distances from the Ethiopian 2016 demographic and health survey (EDHS) clusters to the closest health facility. We computed the distance in ESRI ArcGIS Version 10.3 using the geographic coordinates of DHS clusters and health facilities. Generalised Structural Equation Modelling (GSEM) was used to estimate the effect of distance on neonatal mortality.

Results

Poor geographic accessibility to health facilities affects maternal service usage and increases the risk of newborn mortality. For every ten kilometres (km) increase in distance to a health facility, the odds of neonatal mortality increased by 1.33% (95% CI: 1.06% to 1.67%). Distance also negatively affected antenatal care, facility delivery and postnatal counselling service use.

Conclusions

A lack of geographical access to health facilities decreases the likelihood of newborns surviving their first month of life and affects health services use during pregnancy and immediately after birth. The study also showed that antenatal care use was positively associated with facility delivery service use and that both positively influenced postnatal care use, demonstrating the interconnectedness of the components of continuum of care for maternal and neonatal care services. Policymakers can leverage the findings from this study to improve accessibility barriers to health services.
Insurance-based disparities in breast cancer treatment pathways in a universal healthcare system: a qualitative study
Authors: Kesici Zeynep , Yilmaz Volkan
Published: February 2023

Background

The influence of healthcare system factors on treatment pathways for breast cancer has been studied extensively in lower-middle-income countries (LMICs), but in upper-middle-income countries (UMICs), this area is understudied. This article focuses on the experiences of breast cancer patients in Türkiye, a UMIC with a universal healthcare system. It explores variations in treatment pathways based on the type of health insurance provider (private or state).

Methods

The study uses an exploratory qualitative method based on in-depth interviews with 12 breast cancer patients. The inclusion criteria were Turkish nationality, female gender, and having received treatment from a private hospital within one year of the interview. A purposeful sampling strategy was employed to recruit patients who had either social health insurance only or who had private health insurance in addition to their social health insurance. A two-stage thematic analysis of the interview data was conducted. First, we examined whether the type of insurance provider makes a difference in treatment pathways; we then identified healthcare system factors that explain these differences.

Results

The study revealed two distinct pathways to treatment. These differ in terms of financial protection, service coverage, and patients’ sense of equity. Patients with private insurance reported easy access to timely and comprehensive treatment. Those without, however, had to navigate complicated routes to treatment; they generally had to resort to seeking treatment from more than one hospital. We found two healthcare system factors that explained the differences: a failure to fully enforce the mandates of the state’s social health insurance in the private hospital sector and growing reliance on private insurance to gain access to essential services.

Conclusions

Based on data from the Turkish case, we conclude that healthcare system factors are indeed influential in shaping treatment pathways for breast cancer in UMICs with universal healthcare. These factors include a failure to fully enforce the mandates of the state’s social health insurance programme in the private hospital sector and a growing reliance on private insurance to gain access to essential services. We note that this contrasts dramatically with the situation in LMICs, where the main factors are low-quality care and shortages of medical staff, medicines, and technologies.
Pattern of OPD utilisation during the COVID-19 pandemic under the Universal Coverage Scheme in Thailand: what can 850 million records tell us?
Authors: Sukmanee Jarawee , Butchon Rukmanee , Karunayawong Picharee , Saeraneesopon Thanayut , Boonma Chulathip , Teerawattananon Yot , Isaranuwatchai Wanrudee
Published: February 2023

Background

Out-patient department (OPD) is a crucial component of the healthcare systems in low- and middle-income countries including Thailand. A considerable impact of coronavirus disease 2019 (COVID-19) pandemic and its control measures, especially the lockdown, on utilisation of OPD services was expected. This study thus aims to estimate the pattern of OPD utilisation during the COVID-19 pandemic in Thailand including overall utilisation and within each sub-groups including diagnostic group, age group, and health region.

Methods

This study was a secondary data analysis of aggregated outpatient data from patients covered under the Universal Coverage Scheme (UCS) in Thailand over a 4-year period (2017–2020). Interrupted time series analyses and segmented Quasi-Poisson regression were used to examine the impact of COVID-19 on the overall OPD utilisation including the impact on each diagnostic group, age groups, health regions, and provinces.

Results

Analysis of 845,344,946 OPD visits in this study showed a seasonal pattern and increasing trend in monthly OPD visits before the COVID-19 pandemic. A 28% (rate ratio (RR) 0.718, 95% confidence interval (CI): 0.631–0.819) and 11% (RR 0.890, 95% CI: 0.811–0.977) reduction in OPD visits was observed during the lockdown and post-lockdown periods, respectively, when compared to the pre-lockdown period. Diseases of respiratory system were most affected with a RR of 0.411 (95% CI: 0.320–0.527), while the number of visits for non-communicable diseases (ICD-10: E00–E90, I00–I99) and elderly (> 60 years) dropped slightly. The post-lockdown trend in monthly OPD visits gradually increased to the pre-pandemic levels in most groups.

Conclusions

Thailand’s OPD utilisation rate during the COVID-19 lockdown decreased in some diseases, but the service for certain group of patients appeared to remain available. After the COVID-19 lockdown, the rate returned to the pre-pandemic level in a timely manner. Equipped with a knowledge of OPD utilisation pattern during COVID-19 based on a national real-world database could aid with a better preparation of healthcare system for future pandemics.
The effects of Ginger (Zingiber officinale) roots on the reproductive aspects in male Japanese Quails (Coturnix coturnix japonica)
Authors: Abdelfattah Mostafa Galal , Hussein Manal T. , Ragab Sohair M. M. , Khalil Nasser S. Abou , Attaai Abdelraheim H.
Published: February 2023

Background

The Japanese quail is considered one of the most significant species in the poultry industry. However, the high male-to-female ratio results in the aggressive behavior of males. Dietary strategies that improve the properties of semen could reduce the number of males required to maintain optimal fertility and reduce aggressive behavior. Therefore, this study aims to provide insight into the possible improving efm fect of ginger roots on the reproductive aspects of Japanese male quails.

Results

To achieve this objective, powder of Ginger roots was administrated to 2 groups of quails (10, and 15 g/Kg feed) from 7 days until 70 days of age. Some males were reared singly in cages (n = 40 for each group) to assess sperm quality and other males (n = 32 for each group) were raised with females to assess fertility and sperm-egg penetration. Additionally, biochemical tests and histological examination were also performed. When compared to the control group, dietary inclusion of Ginger at a dose of 15 g caused more improvement in ejaculate volume, sperm concentration, motility, viability and sperm-egg penetration. Whereas, the motility and fertility percentages of sperms were equipotent in both doses. Dose-dependent increases were found in the cloacal gland area and volume, as well as foam production and weight. Both doses resulted in a significant reduction in plasma total cholesterol along with an elevation cin plasma testosterone and lipid peroxides. The comparison between all groups concerning nitric oxide, catalase, superoxide dismutase, and total antioxidant capacity revealed the absence of significant difference. Morphologically, the diameter of the seminiferous tubules and the height of germinal epithelium significantly increased especially in the higher dose of Ginger.

Conclusions

Ginger roots especially at a dose of 15 gm/kg feed was effective in improving male reproductive performance. These findings are of utmost importance in encouraging the addition of Ginger roots in ration formulation in male quails.
Bisphenol A and bisphenol S both disrupt ovine granulosa cell steroidogenesis but through different molecular pathways
Authors: Téteau Ophélie , Vitorino Carvalho Anaïs , Papillier Pascal , Mandon-Pépin Béatrice , Jouneau Luc , Jarrier-Gaillard Peggy , Desmarchais Alice , Lebachelier de la Riviere Marie-Emilie , Vignault Claire , Maillard Virginie , Binet Aurélien , Uzbekova Svetlana , Elis Sebastien
Published: February 2023

Background

Ovarian granulosa cells (GC) are essential for the development and maturation of a proper oocyte. GC are sensitive to endocrine disruptors, including bisphenol A (BPA) and its analogue bisphenol S (BPS), plasticisers present in everyday consumer products. BPA exhibits greater binding affinity for the membrane oestrogen receptor (GPER) than for the nuclear oestrogen receptors (ERα and ERβ). Here, we analysed the effects of BPA and BPS on the steroidogenesis of ovine GC in vitro, as well as their early mechanisms of action, the ovine being a relevant model to study human reproductive impairment. Disruption of GC steroidogenesis might alter oocyte quality and consequently fertility rate. In addition, we compared the effects of a specific GPER agonist (G-1) and antagonist (G-15) to those of BPA and BPS. Ewe GC were cultured with BPA or BPS (10 or 50 µM) or G-1 (1 µM) and/or G-15 (10 µM) for 48 h to study steroidogenesis.

Results

Both BPA and BPS (10 µM) altered the secretion of progesterone, however, only BPS (10 µM) affected oestradiol secretion. RNA-seq was performed on GC after 1 h of culture with BPA or BPS (50 µM) or G-1 (10 µM), followed by real-time PCR analyses of differentially expressed genes after 12, 24 and 48 h of culture. The absence of induced GPER target genes showed that BPA and BPS did not activate GPER in GC after 1 h of treatment. These molecules exhibited mainly independent early mechanisms of action. Gene ontology analysis showed that after 1 h of treatment, BPA mainly disrupted the expression of the genes involved in metabolism and transcription, while BPS had a smaller effect and impaired cellular communications. BPA had a transient effect on the expression ofCHAC1(NOTCH signalling and oxidative balance),JUN(linked to MAPK pathway),NR4A1(oestradiol secretion inhibition),ARRDC4(endocytose of GPCR) andKLF10(cell growth, differentiation and apoptosis), while expression changes were maintained over time for the genesLSMEM1(linked to MAPK pathway),TXNIP(oxidative stress) andLIF(cell cycle regulation) after 12 and 48 h, respectively.

Conclusion

In conclusion, although they exhibited similar effects, BPA and BPS impaired different molecular pathways in GC in vitro. New investigations will be necessary to follow the temporal changes of these genes over time, as well as the biological processes involved.
Dead space ventilation-related indices: bedside tools to evaluate the ventilation and perfusion relationship in patients with acute respiratory distress syndrome
Authors: Zheng Mingjia
Published: February 2023

Cumulative evidence has demonstrated that the ventilatory ratio closely correlates with mortality in acute respiratory distress syndrome (ARDS), and a primary feature in coronavirus disease 2019 (COVID-19)-ARDS is increased dead space that has been reported recently. Thus, new attention has been given to this group of dead space ventilation-related indices, such as physiological dead space fraction, ventilatory ratio, and end-tidal-to-arterial PCO2ratio, which, albeit distinctive, are all global indices with which to assess the relationship between ventilation and perfusion. These parameters have already been applied to positive end expiratory pressure titration, prediction of responses to the prone position and the field of extracorporeal life support for patients suffering from ARDS. Dead space ventilation-related indices remain hampered by several deflects; notwithstanding, for this catastrophic syndrome, they may facilitate better stratifications and identifications of subphenotypes, thereby providing therapy tailored to individual needs.
Analysis of microbial community and biodeterioration of maritime cultural relics (ironware, porcelain, axes, hull wood) from the Nanhai No. 1 shipwreck
Authors: Pan Jiao , Han Yeqing , Wang Cen , Du Jing , Wang Yu , Chen Yue , Huang Xinduo , Ma Kaixuan , Zhang Zhiguo , Li Naisheng
Published: February 2023

Purpose

Maritime cultural relics from the Nanhai No. 1 shipwreck were immersed in a buffer to maintain stability. To better monitor the changes in the composition of microorganisms in the buffer and, thus, prevent the damage to artifacts caused by harmful microorganisms.

Methods

In September and November 2019, we conducted high-throughput sequencing of water samples from four types of maritime cultural relics (ironware, porcelain, axe, and hull wood) to reveal the composition and changes in microbial communities. In addition, we isolated culturable microorganisms and conducted biocide sensitivity tests and lignin and cellulose degradation tests.

Results

Visible microbial colonization was observed in the water samples collected from the buffer solutions of ironware, porcelain, axe, and hull wood of the Nanhai No. 1 shipwreck; additionally, apparent differences in the composition of microorganisms in the water samples collected from different cultural relics and different collection times of the same cultural relics were noted. Few species of bacteria and fungi from the microbial community observed in the maritime cultural relics were cultured, and it was noted that various biocides had certain inhibitory effects on them. Some dominant strains had lignin and cellulose degradation abilities and could only grow under specific environmental conditions.

Conclusion

We found apparent differences in the composition of microorganisms obtained from different cultural relics and different collection times of the same cultural relics. This study can provide data support for better protection of maritime cultural relics obtained from the Nanhai No. 1 shipwreck and provide a theoretical basis for the biological protection of other maritime cultural relics.
Warming changes the composition and diversity of fungal communities in permafrost
Authors: Jiang Yunbing , Yang Libin , Wu Song , Zhou Tian
Published: February 2023

Purpose

It is the data support and theoretical basis for the response mechanism of soil fungi to climate warming in permafrost areas in the Greater Xing’an Mountains.

Methods

We collected permafrost from the Greater Xing’an Mountains for indoor simulation experiments and took the natural permafrost as the control (CK) and the test groups of 0 °C (T1), 2 °C (T2), and 4 °C (T3) were set. Illumina MiSeq high-throughput sequencing technology was used to understand the changes in characteristics of fungal communities, and the correlations were analyzed combined with the soil physicochemical properties.

Results

Compared with CK, the value of pH and the content of available potassium (AK) in the three warming treatment groups were significantly lower (P < 0.05), and the microbial biomass carbon (MBC) content was significantly higher (P < 0.05). The content of total nitrogen (TN) and available nitrogen (AN) in the T1 and T3 groups was significantly lower than that in the CK group (P < 0.05). A total of 11 phyla, 39 classes, 89 orders, 187 families, 361 genera, and 522 species were obtained through fungal sequencing and divided into 1463 amplicon sequence variants (ASVs). Ascomycota and Dimorphospora were the dominant phylum and genus, respectively, and there were differences in the response of relative abundance of various groups at the phylum and genus levels to warming. Warming significantly decreased the Sobs and ACE indexes of the treatment groups (P < 0.05), and the Shannon and Shannoneven indexes also showed a downward trend. Moreover, warming significantly changed the fungal beta diversity (P < 0.01), while the value of pH and the content of TN, MBC, and AK could significantly affect the community structure (P < 0.05), and the correlation between fungi at different phyla levels and soil physicochemical properties was different.

Conclusions

These results can provide a reference for further study on the changes in composition and structure of fungal communities and the influence factor in permafrost in the Greater Xing’an Mountains under the background of warming.
Murine skin-derived multipotent papillary dermal fibroblast progenitors show germline potential in vitro
Authors: Ge Wei , Sun Yuan-Chao , Qiao Tian , Liu Hai-Xia , He Tao-Ran , Wang Jun-Jie , Chen Chun-Lei , Cheng Shun-Feng , Dyce Paul W. , De Felici Massimo , Shen Wei
Published: February 2023

Background

Many laboratories have described the in vitro isolation of multipotent cells with stem cell properties from the skin of various species termed skin-derived stem cells (SDSCs). However, the cellular origin of these cells and their capability to give rise, among various cell types, to male germ cells, remain largely unexplored.

Methods

SDSCs were isolated from newborn mice skin, and then differentiated into primordial germ cell-like cells (PGCLCs) in vitro. Single-cell RNA sequencing (scRNA-seq) was then applied to dissect the cellular origin of SDSCs using cells isolated from newborn mouse skin and SDSC colonies. Based on an optimized culture strategy, we successfully generated spermatogonial stem cell-like cells (SSCLCs) in vitro.

Results

Here, using scRNA-seq and analyzing the profile of 7543 single-cell transcriptomes from newborn mouse skin and SDSCs, we discovered that they mainly consist of multipotent papillary dermal fibroblast progenitors (pDFPs) residing in the dermal layer. Moreover, we found that epidermal growth factor (EGF) signaling is pivotal for the capability of these progenitors to proliferate and form large colonies in vitro. Finally, we optimized the protocol to efficiently generate PGCLCs from SDSCs. Furthermore, PGCLCs were induced into SSCLCs and these SSCLCs showed meiotic potential when cultured with testicular organoids.

Conclusions

Our findings here identify pDFPs as SDSCs derived from newborn skin and show for the first time that such precursors can be induced to generate cells of the male germline.
Acceptability of neural stem cell therapy for cerebral palsy: survey of the Australian cerebral palsy community
Authors: Smith Madeleine J. , Finch-Edmondson Megan , Miller Suzanne L. , Webb Annabel , Fahey Michael C. , Jenkin Graham , Paton Madison Claire Badawy , McDonald Courtney A.
Published: February 2023

Background

Neural stem cells (NSCs) have the potential to engraft and replace damaged brain tissue, repairing the damaged neonatal brain that causes cerebral palsy (CP). There are procedures that could increase engraftment of NSCs and may be critical for efficacy, but hold notable risks. Before clinical trials progress, it is important to engage with the CP community to understand their opinions. The aim of this study was to determine the acceptability of NSC therapy for CP in the CP community.

Methods

Australian residents with CP and parents/carers of those with CP completed a questionnaire to determine their willingness to use NSCs from three sources (fetal, embryonic and induced pluripotent stem cells) and their willingness to undergo accompanying procedures (neurosurgery, immunosuppression) that carry potential risks. To further explore their views, participants also answered free text questions about their ethical concerns regarding the source of NSCs and their perceptions of meaningful outcomes following NSC treatment.

Results

In total, 232 responses were analyzed. Participants were willing to use NSCs from all three cell sources and were willing to undergo NSC therapy despite the need for neurosurgery and immunosuppression. Participants identified a range of outcome domains considered important following NSC treatment including gross motor function, quality of life, independence and cognitive function.

Conclusions

Hypothetical NSC therapy was acceptable to the Australian CP community. This study has identified important findings from the CP community which can be used to inform future NSC research, including the design of clinical trials which may help to increase recruitment, compliance and participant satisfaction.
Explainable uncertainty quantifications for deep learning-based molecular property prediction
Authors: Yang Chu-I , Li Yi-Pei
Published: February 2023

Quantifying uncertainty in machine learning is important in new research areas with scarce high-quality data. In this work, we develop an explainable uncertainty quantification method for deep learning-based molecular property prediction. This method can capture aleatoric and epistemic uncertainties separately and attribute the uncertainties to atoms present in the molecule. The atom-based uncertainty method provides an extra layer of chemical insight to the estimated uncertainties, i.e., one can analyze individual atomic uncertainty values to diagnose the chemical component that introduces uncertainty to the prediction. Our experiments suggest that atomic uncertainty can detect unseen chemical structures and identify chemical species whose data are potentially associated with significant noise. Furthermore, we propose a post-hoc calibration method to refine the uncertainty quantified by ensemble models for better confidence interval estimates. This work improves uncertainty calibration and provides a framework for assessing whether and why a prediction should be considered unreliable.

Graphical Abstract
SESNet: sequence-structure feature-integrated deep learning method for data-efficient protein engineering
Authors: Li Mingchen , Kang Liqi , Xiong Yi , Wang Yu Guang , Fan Guisheng , Tan Pan , Hong Liang
Published: February 2023

Deep learning has been widely used for protein engineering. However, it is limited by the lack of sufficient experimental data to train an accurate model for predicting the functional fitness of high-order mutants. Here, we develop SESNet, a supervised deep-learning model to predict the fitness for protein mutants by leveraging both sequence and structure information, and exploiting attention mechanism. Our model integrates local evolutionary context from homologous sequences, the global evolutionary context encoding rich semantic from the universal protein sequence space and the structure information accounting for the microenvironment around each residue in a protein. We show that SESNet outperforms state-of-the-art models for predicting the sequence-function relationship on 26 deep mutational scanning datasets. More importantly, we propose a data augmentation strategy by leveraging the data from unsupervised models to pre-train our model. After that, our model can achieve strikingly high accuracy in prediction of the fitness of protein mutants, especially for the higher order variants (> 4 mutation sites), when finetuned by using only a small number of experimental mutation data (< 50). The strategy proposed is of great practical value as the required experimental effort, i.e., producing a few tens of experimental mutation data on a given protein, is generally affordable by an ordinary biochemical group and can be applied on almost any protein.