bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of mortality among neonates hospitalized with neonatal sepsis: a case control study from southern Ethiopia
Authors: Bekele Tadele , Merga Hailu , Tesfaye Tamiru , Asefa Henok
Published: January 2022

Background

Neonatal sepsis, which resulted from bacterial, viral, and fungal invasions of the bloodstream, is the major cause of neonatal mortality and neurodevelopmental impairment among neonates. It is responsible for more than one-third of neonatal deaths in Ethiopia. Frequently neonates referred to health facilities are at high risk of death. Hence, assessing and preventing the predictors of mortality in neonatal sepsis helps to reduce the burden of neonatal mortality.

Objectives

To determine predictors of mortality among neonates admitted with sepsis at Durame general hospital, southern Ethiopia, 2020.

Methods

Institution-based unmatched case-control study was carried out from March 8 to 30, 2020, among 219 neonates in Durame general hospital in southern Ethiopia. Neonates admitted with sepsis and died were considered as cases and neonates admitted with sepsis and survived (discharged alive) as controls. Cases were selected by taking the deaths of neonates consecutively among those neonates admitted with the diagnosis of neonatal sepsis. The next immediate three corresponding controls were selected by lottery method from the Neonatal Intensive Care Unit (NICU) case registration book. Data was collected by using structured pretested checklists from neonates’ records and then entered into Epi data version 3.1 and exported to SPSS version 20. Logistic regression was used to identify the predictors of mortality. Statistical significance was declared atP < 0.05.

Results

A total of 55 cases and 164 controls were included in this study. More than three quarters (81.8%) of cases had early onset sepsis. The multivariable logistic regression analysis showed that predictors of mortality in this study were; poor feeding [AOR = 4.15; 95% CI (1.64, 10.49)], respiratory distress [AOR = 2.72; 95% CI (1.31, 5.61)], estimated gestational age less than 37 weeks [AOR = 4.64; 95% CI (2.17, 9.91)], and convulsion [AOR = 3.13; 95% CI (1.12, 8.76)].

Conclusion

This study showed that prematurity, convulsion, poor feeding, and respiratory distress were the predictors of sepsis-related neonatal mortality. It is important to pay attention to septicemic babies with any of the identified predictors to reduce sepsis-related mortality.
Non-parental caregivers, low maternal education, gastrointestinal problems and high blood lead level: predictors related to the severity of autism spectrum disorder in Northeast China
Authors: Dong Han-Yu , Feng Jun-Yan , Li Hong-Hua , Yue Xiao-Jing , Jia Fei-Yong
Published: January 2022

Background

The prevalence of autism spectrum disorder (ASD) has increased rapidly in recent years. Environmental factors may play an important role in the pathogenesis of ASD. These factors may include socioeconomic factors, nutritional factors, heavy metal exposure, air pollution, etc. Our aim is to analyze possible environmental factors associated with the severity of ASD.

Methods

All participating children were divided into two groups (mild and moderate/severe) according to the severity of their symptoms, as determined by their Childhood Autism Rating Scale (CARS) scores. The socioeconomic, demographic factors and the nutritional factors that may affect the severity of ASD were included in the logistic regression to analyze whether they were predictors that affected the severity of ASD.

Results

Logistic regression showed that caregivers(P = 0.042), maternal education (P = 0.030), gastrointestinal problems (P = 0.041) and a high serum concentration of lead (P = 0.003) were statistically significantly associated with ASD severity.

Conclusion

Many environmental factors affect the severity of ASD. We concluded that non-parental caregivers, low maternal education, gastrointestinal problems and high blood lead level maybe predictors that affected the severity of ASD in northeast China.
Clinical study of recurrent mild encephalitis/encephalopathy with a reversible splenial lesion in two cases
Authors: Xue Jiao , Duan Chongfeng , Xu Guizhi , Zhang Ying , Song Zhenfeng , Yi Zhi , Yang Chengqing , Li Fei , Liu Kaixuan , Zhao Hongshan , Liu Xuejun
Published: January 2022

Background

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has been reported worldwidely. However, the data about recurrent cases is limited. We aimed to analyze the clinical and radiographic features of recurrent MERS, and its possible mechanisms.

Case presentation

Two patients with clinically recurrent MERS were reported here, exhibiting neurological symptoms such as limbs weakness and numbness, stand/walk unsteadily, slurred speech and irritability, and typical lesions in the corpus callosum and white matter. One of them experienced another four episodes with a similar clinical course and magnetic resonance imaging findings over a period of 10 years. The Na levels in the present two patients were normal.

Discussion and conclusion

Combined with the patients reported previously, recurrence could be seen in both MERS type 1 and type 2 patients, from two to multiple times, with the latter possibly more common. It suggested that some genetic factors might be involved in MERS, especially for MERS type 2 or familial MERS.
A modified single-endobutton technique combined with nice knot for treatment of Rockwood type III or V acromioclavicular joint dislocation
Authors: Hu Fangning , Han Shumei , Liu Fanxiao , Wang Zhuang , Jia Honglei , Wang Fu , Hu Lingfei , Chen Jing , Wang Bomin , Yang Yongliang
Published: January 2022

Purpose

Double-endobutton technique, as a widely accepted strategy for the treatment of acromioclavicular joint dislocation, is undergoing constant improvement. This study aims to assess the clinical effect of a modified single-endobutton combined with the nice knot in the fixation of Rockwood type III or V acromioclavicular joint dislocation.

Methods

From January 2016 to June 2019, 16 adult patients (13 males and 3 females) with Rockwood type III or V acromioclavicular joint dislocation were treated with a modified single-endobutton technique combined with the nice knot in our department. The age ranged from 18 to 64 years old with an average of 32.8 years old. Operative time, intraoperative blood loss, post-operative clinical outcomes and radiographic results were recorded and analyzed. Preoperative and last follow-up scores in the Constant-Murley Scale, Neer score, Rating Scale of the American Shoulder and Elbow Surgeons and VAS scale and complications such as infection, re-dislocation, implant loosening, medical origin fracture and hardware pain were recorded and evaluated.

Results

Sixteen patients were followed up for 6 to 18 months with an average of 10.3 months. The operative time was 50–90 min with an average of (62.5 ± 3.10) min. The intraoperative blood loss was 30–100 ml, with an average of (55.0 ± 4.28) ml. The complications, such as wound infection, internal fixation failure and fractures, were not found in these cases. According to Karlsson criteria, there were excellent in 14 cases, good in 2 cases at the final follow-up. The mean VAS score of the patients was 5.88 ± 0.26 preoperatively, compared with 0.19 ± 0.14 at the final follow-up evaluation. The difference was statistically significant (P < 0.05). The mean Constant score was 45.5 ± 2.0 preoperatively, compared to 94.0 ± 0.73 at the final follow-up evaluation. The difference was statistically significant (P < 0.05). Patients had statistically significant preoperative and postoperative AC (acromioclavicular distance) and CC (coracoclavicular distance) distances (P < 0.05); 6 months postoperatively the AC(P = 0.412) and CC(P = 0.324) distances were not statistically significant compared to the healthy side.

Conclusion

Nice knot provides a reliable fixation for the single-endobutton technique in the treatment of acromioclavicular dislocations. The modified single-endobutton technique combined with the nice knot can achieve good clinical outcomes in the treatment of Rockwood type III or V acromioclavicular joint dislocation.
Parathyroid hormone enhances gap healing and osseointegration in orthopedic porous coated titanium implants: a correlative micro-computed tomographic, histomorphometric and biomechanical analysis
Authors: Gao Xinlin , Meng Yang , Hao Dingjun , Liu Hao
Published: January 2022

Background

Parathyroid hormone, with its anabolic effect on bone formation, has shown excellent outcomes of curing postmenopausal osteoporosis as well as enhancing osseointegration around orthopaedic and stomatologic implants.The purpose of the present study is to test if low-dose intermittent PTH (1–34) treatment could achieve a satisfactory osseointegration in 2-mm peri-implant gaps, as to provide a new idea for improving the stability of such prosthesis, which will be of great clinical value.

Methods

A custom-made titanium implant was implanted on the calvarium of New Zealand White rabbits. 48 male rabbits were randomly divided into control and PTH group. PTH group received subcutaneous injection of PTH (20 μg/day, 5 days/week). Animals were sacrificed at 4 and 8 weeks after surgery. Quantitative micro-computed tomography, histology and biomechanical pull-out testing were performed to evaluate the gap healing at implantation site.

Results

Analysis of micro-computed tomography demonstrated that PTH group achieved more new bone formation in 2-mm gaps and on bone-implant interface. Quantitatively, significant differences were observed between two groups in regard to BIC and BV/TV at each time-point. Histological staining revealed that PTH group had a superiority in trabecular number, thickness, separation and better osseointegration compared to control group. As for biomechanical pull-out testing, PTH group also showed significant improvement of ultimate force than control group.

Conclusions

Low-dose intermittent administration of PTH for 4 and 8 weeks enhances early osseointegration and fixation of orthopedic implants surrounded by a 2-mm gap in terms of increased bone regeneration and mechanical stability. These findings suggest PTH a potential for reducing the postoperative complications of implants by improving bone healing at peri-implant gaps.
HDAC4 mutant represses chondrocyte hypertrophy by locating in the nucleus and attenuates disease progression of posttraumatic osteoarthritis
Authors: Gu Xiaodong , Li Fei , Gao Yangyang , Che Xianda , Li Pengcui
Published: January 2022

Background

The aim of this study was to evaluate whether histone deacetylase 4 S246/467/632A mutant (m-HDAC4) has enhanced function at histone deacetylase 4 (HDAC4) to attenuate cartilage degeneration in a rat model of osteoarthritis (OA).

Methods

Chondrocytes were infected with Ad-m-HDAC4-GFP or Ad-HDAC4-GFP for 24 h, incubated with interleukin-1β (IL-1β 10 ng/mL) for 24 h, and then measured by RT-qPCR. Male Sprague-Dawley rats (n = 48) were randomly divided into four groups and transduced with different vectors: ACLT/Ad-GFP, ACLT/Ad-HDAC4-GFP, ACLT/Ad-m-HDAC4-GFP, and sham/Ad-GFP. All rats received intra-articular injections 48 h after the operation and every 3 weeks thereafter. Cartilage damage was assessed using radiography and Safranin O staining and quantified using the OARSI score. The hypertrophic and anabolic molecules were detected by immunohistochemistry and RT-qPCR.

Results

M-HDAC4 decreased the expression levels of Runx-2, Mmp-13, and Col 10a1, but increased the levels of Col 2a1 and ACAN more effectively than HDAC4 in the IL-1β-induced chondrocyte OA model; upregulation of HDAC4 and m-HDAC4 in the rat OA model suppressed Runx-2 and MMP-13 production, and enhanced Col 2a1 and ACAN synthesis. Stronger Safranin O staining was detected in rats treated with m-HDAC4 than in those treated with HDAC4. The resulting OARSI scores were lower in the Ad-m-HDAC4 group (5.80 ± 0.45) than in the Ad-HDAC4 group (9.67 ± 1.83, P = 0.045). The OARSI scores were highest in rat knees that underwent ACLT treated with Ad-GFP control adenovirus vector (14.93 ± 2.14, P = 0.019 compared with Ad-HDAC4 group; P = 0.003 compared with Ad-m-HDAC4 group). Lower Runx-2 and MMP-13 production, and stronger Col 2a1 and ACAN synthesis were detected in rats treated with m-HDAC4 than in those treated with HDAC4.

Conclusions

M-HDAC4 repressed chondrocyte hypertrophy and induced chondrocyte anabolism in the nucleus. M-HDAC4 was more effective in attenuating articular cartilage damage than HDAC4.
Biomechanical feasibility of semi-rigid stabilization and semi-rigid lumbar interbody fusion: a finite element study
Authors: Wong Chia-En , Hu Hsuan-Teh , Kao Li-Hsing , Liu Che-Jung , Chen Ke-Chuan , Huang Kuo-Yuan
Published: January 2022

Background

Semi-rigid lumbar fusion offers a compromise between pedicle screw-based rigid fixation and non-instrumented lumbar fusion. However, the use of semi-rigid interspinous stabilization (SIS) with interspinous spacer and ligamentoplasty and semi-rigid posterior instrumentation (SPI) to assist interbody cage as fusion constructs remained controversial. The purpose of this study is to investigate the biomechanical properties of semi-rigidly stabilized lumbar fusion using SIS or SPI and their effect on adjacent levels using finite element (FE) method.

Method

Eight FE models were constructed to simulate the lumbosacral spine. In the non-fusion constructs, semi-rigid stabilization with (i) semi-rigid interspinous spacer and artificial ligaments (PD-SIS), and (ii) PI with semi-rigid rods were simulated (PD + SPI). For fusion constructs, the spinal models were implanted with (iii) PEEK cage only (Cage), (iv) PEEK cage and SIS (Cage+SIS), (v) PEEK cage and SPI (Cage+SPI), (vi) PEEK cage and rigid PI (Cage+PI).

Result

The comparison of flexion-extension range of motion (ROM) in the operated level showed the difference between Cage+SIS, Cage+SPI, and Cage+PI was less than 0.05 degree. In axial rotation, ROM of Cage+SIS were greater than Cage+PI by 0.81 degree. In the infrajacent level, while Cage+PI increased the ROM by 24.1, 27,7, 25.9, and 10.3% and Cage+SPI increased the ROM by 26.1, 30.0, 27.1, and 10.8% in flexion, extension, lateral bending and axial rotation respectively, Cage+SIS only increased the ROM by 3.6, 2.8, and 11.2% in flexion, extension, and lateral bending and reduced the ROM by 1.5% in axial rotation. The comparison of the von Mises stress showed that SIS reduced the adjacent IVD stress by 9.0%. The simulation of the strain energy showed a difference between constructs less than 7.9%, but all constructs increased the strain energy in the infradjacent level.

Conclusion

FE simulation showed semi-rigid fusion constructs including Cage+SIS and Cage+SPI can provide sufficient stabilization and flexion-extension ROM reduction at the fusion level. In addition, SIS-assisted fusion resulted in less hypermobility and less von Mises stress in the adjacent levels. However, SIS-assisted fusion had a disadvantage of less ROM reduction in lateral bending and axial rotation. Further clinical studies are warranted to investigate the clinical efficacy and safety of semi-rigid fusions.
The frequency of periodontitis in end-stage renal disease on hemodialysis in a sample of Egyptian population: multi-center clinical cross-sectional study
Authors: Abou-Bakr Asmaa , Hussein Radwa R. , Khalil Eman , Ahmed Enji
Published: January 2022

Background

There is a general assumption that periodontal disease is highly prevalent among patients with chronic renal failure undergoing hemodialysis. The aim of the study to estimate the frequency of periodontitis in patients on hemodialysis among a sample of the Egyptian population, as well as the correlation between different clinical parameters of periodontal status with serum creatinine and blood urea. This may rule out the bidirectional relationship between periodontitis and renal failure in patients on hemodialysis.

Methods

The study was conducted on 263 hemodialysis patients (165 males and 98 females) at three dialysis centers in Benha Governorate, Egypt (Benha Hospital, Tukh hospital, Qalyub hospital). Periodontal parameters including plaque index (PI), gingival index (GI), clinical attachment level (CAL), and probing pocket depth (PPD) had been recorded in these patients. Serum urea and creatinine levels had been measured, the data had been collected and undergone statistical analysis.

Results

Frequency of periodontitis was 85.6% with stage III is the most prevalent stage. There was a significant positive strong correlation between age and periodontitis stage (rs = 0.707, p < 0.001). There was a positive correlation between clinical parameters and serum creatinine level.

Conclusion

In the present study, a high frequency of periodontitis had been found among ESRD patients on hemodialysis in the severe form (stage III) periodontitis. There was a significant direct correlation between the severity of periodontitis and CAL with a duration of hemodialysis. There was a weak insignificant association between periodontal indices (PD, BOP, and plaque score) and duration of hemodialysis.
Economic evaluation of a national vitamin D supplementation program among Iranian adolescents for the prevention of adulthood type 2 diabetes mellitus
Authors: Zandieh Narges , Hemami Mohsen Rezaei , Darvishi Ali , Hasheminejad Seyed Mohammad , Abdollahi Zahra , Zarei Maryam , Heshmat Ramin
Published: January 2022

Background

This study aimed to evaluate the cost-effectiveness of vitamin D supplementation in preventing type 2 diabetes mellitus (T2DM) among Iranian adolescents.

Methods

This analytical observational study was conducted, using the decision tree model constructed in TreeAge Pro to assess the cost per quality-adjusted life-year (QALY) of monthly intake vitamin D supplements to prevent T2DM compared to no intervention from the viewpoint of Iran’s Ministry of Health and through an one-year horizon. In the national program of vitamin D supplementation, 1,185,211 Iranian high-school students received 50,000 IU vitamin D supplements monthly for nine months. The costs-related data were modified to 2018. The average cost and effectiveness were compared based on the Incremental Cost-Effectiveness Ratio (ICER).

Results

Our analytical analysis estimated the 4071.25 (USD / QALY) cost per AQALY gained of the monthly intake of 50,000 IU vitamin D for nine months among adolescents over a one-year horizon. Based on the ICER threshold of 1032–2666, vitamin D supplementation was cost-effective for adolescents to prevent adulthood T2DM. It means that vitamin D supplementation costs were substantially less than the costs of T2DM treatments than the no intervention.

Conclusions

Based on the findings, the national vitamin D supplementation program for Iranian adolescents could be a cost-effective strategy to reduce the risk of diabetes in adulthood. From an economic perspective, vitamin D supplementation, especially in adolescents with vitamin D deficiency, would be administrated.
Construction and practice of a comprehensive nursing skills course with simulation in an RN-BSN program in China: a quasi-experimental study
Authors: Zhu Yuanyuan , Wang Aihong , Bai Yamei , Xu Min , Yin Haiyan , Gao Qinyi
Published: January 2022

Background

Simulation has been widely used in the teaching of pre-licensed nursing students and has shown positive results. However, there is limited evidence regarding the application of a comprehensive nursing course with simulation for Associated Degree in Nursing (ADN)-prepared nurses with different work experience times. Therefore, this study aimed to evaluate the satisfaction, self-confidence, and perceptions of scenario simulation among Chinese nurses in a comprehensive nursing skills course in an RN-BSN program.

Methods

A single-group post-test approach was used in the current study. Participants that completed a comprehensive nursing skills course with simulation in an RN-BSN program were enrolled.

Results

The mean satisfaction, self-confidence, educational practice, and simulation designs scores were rated highly. Self-confidence (p = 0.002), active learning (p = 0.020), collaboration (p = 0.030), support (p = 0.008), and problem-solving (p = 0.007) were significantly higher among students with more work experience compared to those with less experience. Then, four themes were analyzed: enthusiasm for learning, ability to experience different feelings during role-play, hybrid teaching format, and simulation fidelity.

Conclusions

Results demonstrated that a comprehensive nursing skills course with simulation might improve Chinese ADN-prepared nurses’ satisfaction and self-confidence in learning. Nurses with work experience gave a high rate to the scenario simulation, demonstrating that simulation can be widely applicable for students with different characteristics. Finally, the teaching strategy in the present study can be applied to more RN-BSN programs.
Virtual conference participant’s perceptions of its effectiveness and future projections
Authors: Kim Kyong-Jee , Kim Seo Rin , Lee Jangwook , Moon Ju-Young , Lee Sang-Ho , Shin Sung Joon
Published: January 2022

Background

The virtual conference format has become an essential tool for professional development of researchers around the world since the outbreak of the COVID-19 pandemic. This study aims to identify empirical evidence of the benefits and challenges of virtual conferences by investigating participants’ experiences with them.

Methods

The study participants were delegates to the 40th annual meeting of the Korean Society of Nephrology, which was held virtually in September, 2020. A questionnaire was developed and implemented among the conference attendees. The 44-item questionnaire included five sub-scales related to participant perceptions of the virtual conference, which were (a) convenience and accessibility, (b) planning and organization, (c) technology use, (d) social exchanges, and (e) overall satisfaction, their preferences of conference formats, and their views of future projections for a virtual conference.

Results

A total of 279 delegates completed and returned the questionnaires (18.8% response rate). Participants varied in gender, age, profession, work location, and prior experience with conferences. On a four-point Likert scale (1 = “strongly disagree” and 4 = “strongly agree”), participants showed positive perceptions of the virtual conference in general, where the total mean (M) was 3.03 and less positive perceptions on social exchanges (M = 2.72). Participant perceptions of the virtual conference differed across age groups, professions, and prior experience with conferences (p < .05). Approximately half of the participants (n = 139) preferred the virtual format, and 33% (n = 92) preferred the conventional format. Participant preferences for the virtual format were somewhat evenly distributed between asynchronous (32.9%) and synchronous (29.1%) modes. Participants predicted a virtual conference would continue to be a popular delivery format after the end of the COVID-19.

Conclusions

Although participants had positive perceptions of the virtual conference, more support needs to be offered to those who may be less comfortable with using technology or with online interactions, and there is a need for improvement in supporting social exchange among attendees. Also, it is suggested that a blend of asynchronous and synchronous delivery methods should be considered to meet the varied needs of attendees.
Undergraduate-level teaching and learning approaches for interprofessional education in the health professions: a systematic review
Authors: Aldriwesh Marwh Gassim , Alyousif Sarah Mohammed , Alharbi Nouf Sulaiman
Published: January 2022

Background

Although most systematic reviews of interprofessional education (IPE) evaluated the impact of IPE on the students’ acquisition of knowledge in relation to other professions, the development of teamwork skills, and the changes in collaborative behaviour, the processes involved in IPE (i.e., approaches to teaching and learning) are under-researched. The purpose of the study was to conduct a systematic review to establish how IPE has been implemented in university-based undergraduate curricula, focusing on the teaching and learning approaches.

Methods

The systematic review was performed in 2020 with three databases: PubMed, Science Direct, and the Cochrane Library. Titles and abstracts were included based on pre-identified eligibility criteria. We used the article entitled ‘Systematic reviews in medical education: a practical approach: AMEE guide 94’ as the basis to establish the aim and methods of the current systematic review from 2010 to 2019.

Results

We found 16 articles that met the inclusion criteria and reported the implementation process of IPE in universities from Western, Asian, and African countries. A combination of at least two teaching and learning approaches was used to deliver IPE. The findings indicated that of all the teaching and learning approaches, simulation-based education, e-learning, and problem-based learning were the most prevalent approaches used to deliver IPE. This systematic review also revealed a lack of IPE programmes in the Middle East region.

Conclusions

The evidence synthesised in the current systematic review could support IPE curriculum planners and educators when planning an IPE programme. More global IPE initiatives are required to meet the global health workforce needs. Further studies are required to identify the effectiveness of the different teaching and learning approaches in the development of IPE competencies.
Empathy, personality traits, and emotional management in 2nd and 4th-year dentistry students: a single-center study
Authors: Lermen Christian , Wetzel Willi , Britz Vanessa , Sterz Jasmina , Bechstein Wolf O , Schreckenbach Teresa
Published: January 2022

Background

Patients fearing dental interventions are at risk of delaying or skipping much-needed treatments. Empathic communication could lead to a higher rate of compliance from patients within this group. Empathy, the big five personality traits, and emotion management abilities are all known to influence the quality of communication between dentists and patients. This study was conducted to analyze whether there is a correlation between these factors in dentistry students.

Methods

Dentistry students in their 2nd and 4th year of study were asked to complete questionnaires assessing empathy, emotion management, and personality traits. Out of a total of 148 eligible participants, 53 students (34%) volunteered to participate. For empathy, the Jefferson Scale of Physician Empathy (students’ version; JSPE-S) and the Interpersonal Reactivity Index (IRI) were used. Personality traits were assessed using the Short Big Five Inventory (BFI-s), and the Situational Test of Emotional Management (STEM) to measure emotional management ability.

Results

Higher scores for emotion management were significantly correlated with the female gender (p ≤ 0.005) and with higher scores in openness (p ≤ 0.05). Students with higher scores in openness also achieved higher scores on the IRI subscales: Perspective taking (p ≤ 0.05), Fantasy (p ≤ 0.01), Empathic concern (p ≤ 0.05), and Personal distress (p ≤ 0.05). For JSPE-S, no correlation with emotion management and personality traits was found.

Conclusion

Empathy and emotion management might not be significantly related in dentistry students. Regarding personality traits, students who scored higher on openness also indicated higher abilities in emotion management. These findings should be taken into consideration when planning communication courses for dentistry students, as it might be possible to independently train empathy and emotion management as part of emotional intelligence.
Chemical composition and physical characteristics of faeces in horses with and without free faecal liquid – two case-control studies
Authors: Lindroth K. M. , Dicksved J. , Vervuert I. , Müller C. E.
Published: January 2022

Background

Free faecal liquid (FFL) is a condition in horses characterised by two-phase (one solid and one liquid) separation of faeces. Causes of the condition are unknown, but disturbed hindgut fermentation has been suggested as it may alter biochemical composition and appearance of faeces in equines. However, information on faecal composition in horses with FFL is scarce. Faecal chemical composition (dry matter, osmolality, ash, macro minerals, short-chain fatty acids (SCFA) and pH) and physical characteristics (free liquid, sand, water holding capacity and particle size distribution) were compared in horses with (case) and without (control) FFL in two sub-studies. In sub-study I, faeces from 50 case-control horse pairs in Sweden and Norway were sampled in three sampling periods (SP1-SP3). In sub-study II, faeces from 32 case-control horse pairs in Germany were sampled on one occasion.

Results

In sub-study I, faecal concentration and proportion of lactic acid (of total short-chain fatty acids, SCFA) and water holding capacity was lower in case compared to control horses. Other variables (content of dry matter, ash, sodium, calcium, phosphorous, magnesium, sulphur, and concentrations of i-butyric, n-valeric and total SCFA, ammonia-N as proportion of total N, and pH) were similar in faeces from case and control horses. In sub-study II, all analysed variables were similar in faecal samples from case and control horses. Faecal particle size distribution was similar in case and control horses, but the proportion of larger particles (2 and 1 mm) were lower and proportion of smaller particles (< 1 mm) was higher in sub-study I compared to in sub-study II.

Conclusions

To the authors’ knowledge, this is the first study to investigate faecal chemical composition and physical characteristics in horses with FFL. Case and control horses had similar total SCFA, pH and osmolality, indicating that hindgut fermentation was similar. However, small differences in concentration and proportion (of total SCFA) of lactic acid and water holding capacity of faeces were shown and are of interest for further studies of horses with FFL.
Sophorolipid protects against early-weaning syndrome by improving the gut microenvironment in early-weaned piglets
Authors: Kwak Min-Jin , Choi Sun-Woo , Choi Yong-Soon , Lee Hanbae , Whang Kwang-Youn
Published: January 2022

Background

In animals, weaning stress is the first and most critical stress. Weaning can negatively affect the growth performance of animals physically, psychologically, and pathologically. Our previous studies on the HT-29 cell line and early-weaned rats demonstrated that adequate sophorolipid (SPL) supplementation in feed could enhance the mucin-producing and wound healing capacities of the gut defense system by modulating gut microbiota.

Methods

We conducted an experiment with one hundred forty 21-day-old early weaned piglets (L x Y x D). They were allocated into 4 treatment and 7 replications (4 pigs per pen) according to their initial body weight. Body weight and feed intake were measured biweekly during experimental period. After 6 weeks, 28 pigs were randomly selected and sacrificed to collect plasma, jejunum, and cecal content samples.

Results

Dietary SPL supplementation at 5 and 10 mg/kg quadratically increased the average daily gain during the experimental period in the treatment groups when compared with the control group. The albumin levels of piglets fed with the SPL supplemented diet were downregulated to the normal range. Moreover, in feed, SPL supplementation at 5 and 10 mg/kg improved jejunal histological indices and gene expression levels related to mucin secretion and local inflammation markers. Consistent with these results, adequate SPL supplementation (5 and 10 mg/kg) increased the population of Prevotella, a beneficial bacterium, and its short-chain fatty acid production in the ceca of piglets.

Conclusions

The occurrence of diarrhea after weaning in piglets could be reduced by feeding a 10 ppm of SPL supplemented diet which improves the gut defense system by improving the microbial population and enhancing mucin layer integrity.
The frequency of the known mitochondrial variants associated with drug-induced toxicity in a Korean population
Authors: Pham Vinh Hoa , Nguyen Van Lam , Jung Hye-Eun , Cho Yong-Soon , Shin Jae-Gook
Published: January 2022

Background

Few studies have annotated the whole mitochondrial DNA (mtDNA) genome associated with drug responses in Asian populations. This study aimed to characterize mtDNA genetic profiles, especially the distribution and frequency of well-known genetic biomarkers associated with diseases and drug-induced toxicity in a Korean population.

Method

Whole mitochondrial genome was sequenced for 118 Korean subjects by using a next-generation sequencing approach. The bioinformatic pipeline was constructed for variant calling, haplogroup classification and annotation of mitochondrial mutation.

Results

A total of 681 variants was identified among all subjects. The MT-TRNP gene and displacement loop showed the highest numbers of variants (113 and 74 variants, respectively). The m.16189T > C allele, which is known to reduce the mtDNA copy number in human cells was detected in 25.4% of subjects. The variants (m.2706A > G, m.3010A > G, and m.1095T > C), which are associated with drug-induced toxicity, were observed with the frequency of 99.15%, 30.51%, and 0.08%, respectively. The m.2150T > A, a genotype associated with highly disruptive effects on mitochondrial ribosomes, was identified in five subjects. The D and M groups were the most dominant groups with the frequency of 34.74% and 16.1%, respectively.

Conclusions

Our finding was consistent with Korean Genome Project and well reflected the unique profile of mitochondrial haplogroup distribution. It was the first study to annotate the whole mitochondrial genome with drug-induced toxicity to predict the ADRs event in clinical implementation for Korean subjects. This approach could be extended for further study for validation of the potential ethnic-specific mitochondrial genetic biomarkers in the Korean population.
Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier
Authors: Vafaei Somayeh , Zekiy Angelina O. , Khanamir Ramadhan Ado , Zaman Burhan Abdullah , Ghayourvahdat Arman , Azimizonuzi Hannaneh , Zamani Majid
Published: January 2022

Recently, immune checkpoint inhibitors (ICIs) therapy has become a promising therapeutic strategy with encouraging therapeutic outcomes due to their durable anti-tumor effects. Though, tumor inherent or acquired resistance to ICIs accompanied with treatment-related toxicities hamper their clinical utility. Overall, about 60–70% of patients (e.g., melanoma and lung cancer) who received ICIs show no objective response to intervention. The resistance to ICIs mainly caused by alterations in the tumor microenvironment (TME), which in turn, supports angiogenesis and also blocks immune cell antitumor activities, facilitating tumor cells' evasion from host immunosurveillance. Thereby, it has been supposed and also validated that combination therapy with ICIs and other therapeutic means, ranging from chemoradiotherapy to targeted therapies as well as cancer vaccines, can capably compromise tumor resistance to immune checkpoint blocked therapy. Herein, we have focused on the therapeutic benefits of ICIs as a groundbreaking approach in the context of tumor immunotherapy and also deliver an overview concerning the therapeutic influences of the addition of ICIs to other modalities to circumvent tumor resistance to ICIs.
A threshold-free approach with age-dependency for estimating malaria seroprevalence
Authors: Kyomuhangi Irene , Giorgi Emanuele
Published: January 2022

Background

In malaria serology analysis, the standard approach to obtain seroprevalence, i.e the proportion of seropositive individuals in a population, is based on a threshold which is used to classify individuals as seropositive or seronegative. The choice of this threshold is often arbitrary and is based on methods that ignore the age-dependency of the antibody distribution.

Methods

Using cross-sectional antibody data from the Western Kenyan Highlands, this paper introduces a novel approach that has three main advantages over the current threshold-based approach: it avoids the use of thresholds; it accounts for the age dependency of malaria antibodies; and it allows us to propagate the uncertainty from the classification of individuals into seropositive and seronegative when estimating seroprevalence. The reversible catalytic model is used as an example for illustrating how to propagate this uncertainty into the parameter estimates of the model.

Results

This paper finds that accounting for age-dependency leads to a better fit to the data than the standard approach which uses a single threshold across all ages. Additionally, the paper also finds that the proposed threshold-free approach is more robust against the selection of different age-groups when estimating seroprevalence.

Conclusion

The novel threshold-free approach presented in this paper provides a statistically principled and more objective approach to estimating malaria seroprevalence. The introduced statistical framework also provides a means to compare results across studies which may use different age ranges for the estimation of seroprevalence.
Randomized trial of a portable HEPA air cleaner intervention to reduce asthma morbidity among Latino children in an agricultural community
Authors: Drieling Rebecca L. , Sampson Paul D. , Krenz Jennifer E. , Tchong French Maria I. , Jansen Karen L. , Massey Anne E. , Farquhar Stephanie A. , Min Esther , Perez Adriana , Riederer Anne M. , Torres Elizabeth , Younglove Lisa R. , Aisenberg Eugene , Andra Syam S. , Kim-Schulze Seunghee , Karr Catherine J.
Published: January 2022

Background

Data on pediatric asthma morbidity and effective environmental interventions in U.S. agricultural settings are few. We evaluated the effectiveness of HEPA air cleaners on asthma morbidity among a cohort of rural Latino children.

Methods

Seventy-five children with poorly controlled asthma and living in non-smoking homes were randomly assigned to asthma education alone or along with HEPA air cleaners placed in their sleeping area and home living room. The Asthma Control Test (ACT) score, asthma symptoms in prior 2 weeks, unplanned clinical utilization, creatinine-adjusted urinary leukotriene E4 (uLTE4 [ng/mg]), and additional secondary outcomes were evaluated at baseline, six, and 12 months. Group differences were assessed using multivariable-adjusted generalized estimating equations. Incident rate ratios of ever experiencing the metrics of poorer asthma health during follow-up (suboptimal asthma management) were estimated using Poisson regression models in secondary analysis.

Results

Mean child age was 9.2 and 8.6 years in intervention and control groups, respectively, and two-thirds of participants were male. Primary analysis of repeated measures of ACT score did not differ between groups (HEPA group mean change compared to controls 10% [95% CI: − 12-39%]). A suggestion of greater decrease in uLTE4 (ng/mg creatinine) was observed (− 10% [95% CI: − 20 -1%]). Secondary analysis showed children with HEPAs were less likely to have an ACT score meeting a clinically defined cutoff for poorly controlled asthma using repeated measures (IRR: 0.45 [95% CI: 0.21–0.97]). In Poisson models, intervention participants had reduced risk of ever meeting this cutoff (IRR: 0.43 [95% CI: 0.21–0.89]), ever having symptoms in the past 2 weeks (IRR: 0.71 [95% CI: 0.52–0.98]), and lower risk of any unplanned clinical utilization (IRR: 0.35 [95% CI: 0.13–0.94]) compared to control participants.

Discussion

The HAPI study showed generally improved outcomes among children in the HEPA air cleaner group. However, primary analyses did not meet statistical significance and many outcomes were subjective (self-report) in this unblinded study, so findings must be interpreted cautiously. HEPA air cleaners may provide additional benefit for child asthma health where traditional asthmagens (traffic, tobacco smoke) are not prominent factors, but larger studies with more statistical power and blinded designs are needed.

Trial registration

ClinicalTrials.gov Identifier: NCT04919915. Date of retrospective registration: May 19, 2021.
Ambient nitrogen dioxide is associated with emergency hospital visits for atrial fibrillation: a population-based case-crossover study in Reykjavik, Iceland
Authors: Halldorsdottir Solveig , Finnbjornsdottir Ragnhildur Gudrun , Elvarsson Bjarki Thor , Gudmundsson Gunnar , Rafnsson Vilhjalmur
Published: January 2022

Background

In Iceland air quality is generally good; however, previous studies indicate that there is an association between air pollution in Reykjavik and adverse health effects as measured by dispensing of medications, mortality, and increase in health care utilisation.

The aim was to study the association between traffic-related ambient air pollution in the Reykjavik capital area and emergency hospital visits for heart diseases and particularly atrial fibrillation and flutter (AF).

Methods

A multivariate time-stratified case-crossover design was used to study the association. Cases were those patients aged 18 years or older living in the Reykjavik capital area during the study period, 2006–2017, who made emergency visits to Landspitali University Hospital for heart diseases. In this population-based study, the primary discharge diagnoses were registered according to International Classification of Diseases, 10th edition (ICD-10). The pollutants studied were NO2, PM10, PM2.5, and SO2, with adjustment for H2S, temperature, and relative humidity. The 24-h mean of pollutants was used with lag 0 to lag 4.

Results

During the study period 9536 cases of AF were identified. The 24-h mean NO2 was 20.7 μg/m3. Each 10 μg/m3 increase in NO2 was associated with increased risk of heart diseases (ICD-10: I20-I25, I44-I50), odds ratio (OR) 1.023 (95% CI 1.012–1.034) at lag 0. Each 10 μg/m3 increase in NO2 was associated with an increased risk of AF (ICD-10: I48) on the same day, OR 1.030 (95% CI: 1.011–1.049). Females were at higher risk for AF, OR 1.051 (95% CI 1.019–1.083) at lag 0, and OR 1.050 (95% CI 1.019–1.083) at lag 1. Females aged younger than 71 years had even higher risk for AF, OR 1.077 (95% CI: 1.025–1.131) at lag 0. Significant associations were found for other pollutants and emergency hospital visits, but they were weaker and did not show a discernable pattern.

Conclusions

Short-term increase in NO2 concentrations was associated with heart diseases, more precisely with AF. The associations were stronger among females, and among females at younger age. This is the first study in Iceland that finds an association between air pollution and cardiac arrhythmias, so the results should be interpreted with caution.
Integrative analysis of CRISPR screening data uncovers new opportunities for optimizing cancer immunotherapy
Authors: Li Yan , Yang Chen , Liu Zhicheng , Du Shangce , Can Susan , Zhang Hailin , Zhang Linmeng , Huang Xiaowen , Xiao Zhenyu , Li Xiaobo , Fang Jingyuan , Qin Wenxin , Sun Chong , Wang Cun , Chen Jun , Chen Huimin
Published: January 2022

Background

In recent years, the application of functional genetic immuno-oncology screens has showcased the striking ability to identify potential regulators engaged in tumor-immune interactions. Although these screens have yielded substantial data, few studies have attempted to systematically aggregate and analyze them.

Methods

In this study, a comprehensive data collection of tumor immunity-associated functional screens was performed. Large-scale genomic data sets were exploited to conduct integrative analyses.

Results

We identified 105 regulator genes that could mediate resistance or sensitivity to immune cell-induced tumor elimination. Further analysis identified MON2 as a novel immune-oncology target with considerable therapeutic potential. In addition, based on the 105 genes, a signature named CTIS (CRISPR screening-based tumor-intrinsic immune score) for predicting response to immune checkpoint blockade (ICB) and several immunomodulatory agents with the potential to augment the efficacy of ICB were also determined.

Conclusion

Overall, our findings provide insights into immune oncology and open up novel opportunities for improving the efficacy of current immunotherapy agents.
A novel imatinib-upregulated long noncoding RNA plays a critical role in inhibition of tumor growth induced by Abl oncogenes
Authors: Ma Yun , Guo Guijie , Li Tingting , Wen Faxin , Yang Jianling , Chen Biao , Wang Xuefei , Chen Ji-Long
Published: January 2022

Background

Dysregulation of long noncoding RNAs (lncRNAs) has been linked to various human cancers. Bcr-Abl oncogene that results from a reciprocal translocation between human chromosome 9 and 22, is associated with several hematological malignancies. However, the role of lncRNAs in Bcr-Abl-induced leukemia remains largely unexplored.

Methods

LncRNA cDNA microarray was employed to identify key lncRNAs involved in Bcr-Abl-mediated cellular transformation. Abl-transformed cell survival and xenografted tumor growth in mice were evaluated to dissect the role of imatinib-upregulated lncRNA 1 (IUR1) in Abl-induced tumorigenesis. Primary bone marrow transformation and in vivo leukemia transplant using lncRNA-IUR1 knockout (KO) mice were further conducted to address the functional relevance of lncRNA-IUR1 in Abl-mediated leukemia. Transcriptome RNA-seq and Western blotting were performed to determine the mechanisms by which lncRNA-IUR1 regulates Bcr-Abl-induced tumorigenesis.

Results

We identified lncRNA-IUR1 as a critical negative regulator of Bcr-Abl-induced tumorigenesis. LncRNA-IUR1 expressed in a very low level in Bcr-Abl-positive cells from chronic myeloid leukemia patients. Interestingly, it was significantly induced in Abl-positive leukemic cells treated by imatinib. Depletion of lncRNA-IUR1 promoted survival of Abl-transformed human leukemic cells in experiments in vitro and xenografted tumor growth in mice, whereas ectopic expression of lncRNA-IUR1 sensitized the cells to apoptosis and suppressed tumor growth. In concert, silencing murine lncRNA-IUR1 in Abl-transformed cells accelerated cell survival and the development of leukemia in mice. Furthermore, lncRNA-IUR1 deficient mice were generated, and we observed that knockout of murine lncRNA-IUR1 facilitated Bcr-Abl-mediated primary bone marrow transformation. Moreover, animal leukemia model revealed that lncRNA-IUR1 deficiency promoted Abl-transformed cell survival and development of leukemia in mice. Mechanistically, we demonstrated that lncRNA-IUR1 suppressed Bcr-Abl-induced tumorigenesis through negatively regulating STAT5-mediated GATA3 expression.

Conclusions

These findings unveil an inhibitory role of lncRNA-IUR1 in Abl-mediated cellular transformation, and provide new insights into molecular mechanisms underlying Abl-induced leukemogenesis.
A review of disparities in access to infertility care and treatment outcomes among Hispanic women
Authors: Komorowski Allison S. , Jain Tarun
Published: January 2022

Hispanic women have lower rates of use of infertility services than non-Hispanic White women. There are many barriers that impede access to infertility care including economic, geographic, cultural, and societal factors and there are disparities in treatment outcomes. Hispanic women are less likely to seek infertility care than non-Hispanic White women and even after infertility evaluation, Hispanic women are less likely to receive treatment for their infertility. Lower use of infertility treatments among Hispanic women is unlikely to be driven solely by economic factors. There is disappointingly little data on in-vitro fertilization treatment outcomes including the population of Hispanic women, and existing data has yielded conflicting results. Incomplete and variable reporting of race data across clinics raises the potential for misclassification bias and invalid study conclusions. Addressing disparities in access to reproductive medicine in the Hispanic population will required a multifaceted approach including expanded insurance coverage, improved education for both patients and providers, and additional research on barriers to care.