bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of ART effects and drug resistance in adult HIV/AIDS patients in Meigu County, Liangshan Prefecture, China
Authors: Yuan Li , Chen Kaiyou , Cai Yuanfang , Zhou Zhonghui , Yang Ju , Jiqu Wuti , Zhu Qirong , Zhang Hong , Niu Shaowei , Sun Hui
Published: February 2024

Background objective

This study aimed to understand the basic situation of adults with human immunodeficiency virus (HIV) receiving antiretroviral therapy (ART) in Meigu County, Liangshan Yi Autonomous Prefecture. The information of patients who had been on ART for more than 6 months, the effect of ART, the possible reasons for ART failure, knowledge of drug resistance among patients with ART failure and the possible reasons for the emergence of drug resistance were analyzed.

Methods

A total of 2753 people living with HIV (PLWH) were collected for HIV-1 RNA virus nucleic acid testing. Plasma specimens with HIV-1 RNA ≥ 1000 copies/mL were sent to the laboratory for nucleic acid extraction, PCR, electrophoresis and sequencing, and the sequencing results were submitted to the HIV drug resistance database of Stanford University for subtyping to determine the drug resistance mutation sites and drug sensitivity levels.

Results

A total of 2753 patients were enrolled in this study. Antiviral therapy failed in 288 patients and was successfully amplified in 245, of which 111 had resistance genes. The resistance rate to failure of viral suppression was 45.3% (111/245). The highest rates of resistance to NNRTIs were found for efavirenz (EFV) and nevirapine (NVP) (42.9%), and the highest rates of resistance to NRTIs were found for 3TC and emtricitabine (FTC) (15.9%). The most common NNRTI resistance mutation site was K103N (20.8%), followed by V179D (9.4%) and V106M (7.8%); the most common NRTI resistance mutation site was M184V/I/MV (14.3%), followed by K65R (6.9%); three PI-associated resistance mutation sites were identified. The subtype of the resistant strain was CRF07-BC in almost all patients (98.9%).

Conclusions

Compared with the previous low ART efficacy in the county, this study showed that the overall virological failure (VF) resistance rate in the county is still low, dominated by resistance to EFV, NVP, 3TC, FTC, and didanosine (DDI). Due to economic constraints, the core regimen is still 3TC + TDF, but before initiating ART, testing for HIV-1 subtypes and resistance should be conducted to avoid resistance that can lead to VF, especially for patients with high risk factors for resistance as shown by epidemiologic investigations.
Benefit finding in chronic kidney disease patients receiving hemodialysis: a cross-sectional study
Authors: Yang Jie , Yan Hong-Li , Li Yong-Qi , Zhang Lei , Qiu Xiao-Yan , Tian Yi-He , Gong Yan-Lin , Luo Chen-Ling , Wu Jing , Chu Jing
Published: February 2024

Background and objectives

The psychological problems of hemodialysis (HD) patients are prominent, and benefit finding (BF) have been proven beneficial to physical and mental health, fewer researchers explored BF in HD patients. The aim of this study was to investigate the current status of BF in patients with chronic kidney disease and to analyze the factors influencing it in order to provide a reference for subsequent interventions.

Methods

A cross-sectional study was done on 246 HD patients by convenience sampling in the hemodialysis center of a 3 A hospital in Shanghai from March to September 2019. The measures include General Information Questionnaire, Benefit Finding Scale, Perceived Social Support Scale, General Self-efficacy Scale, and Simplified Coping Style scale.

Results

The median (interquartile range, IQR) score of BF was 66 (IQR = 19) and it was lower compared with other chronic diseases. Significant differences in BF scores were found between different age groups, HD duration categories, and understanding degrees of HD. Taking BF as the dependent variable, the results of multiple linear regression analysis showed that age, duration of HD, family support, other support, positive coping, and self-efficacy entered the regression equation to explain 43.8% of the total variation. Social support played an indirect effect in the relationship between positive coping and BF, accounting for 54.1% of the total effect.

Conclusion

The BF of HD patients is worrisome and affected by many factors. Medical staff could pay attention to the positive psychology of HD patients, and construct individualized interventions according to the influencing factors to improve their BF level and achieve physical and mental health.
Factors influencing C-reactive protein status on admission in neonates after birth
Authors: Cao Chuanding , Wang Shuo , Liu Yang , Yue Shaojie , Wang Mingjie , Yu Xiaohe , Ding Ying , Lv Mei , Fang Keren , Chu Meiyan , Liao Zhengchang
Published: February 2024

Objective

To explore the factors influencing C-reactive protein (CRP) status in neonates on admission after birth.

Methods

820 newborns born and hospitalized at Xiangya Hospital of Central South University from Jan. 2020 to Dec. 2020 were retrospectively analyzed. Maternal medical history and medication use during pregnancy, neonatal demographic information and status at birth were collected through the electronic medical record system. Statistical software was used to analyze the possible relationship between perinatal factors and CRP on admission after birth.

Results

A total of 820 neonates were analyzed, including 463 males and 357 females with a mean gestational age (GA) of 36.07 ± 3.30 weeks. (1) Multifactor Logistic regression analysis: larger GA (OR: 1.13, 95%CI: 1.00-1.28, P = 0.042), premature rupture of membranes (PROM) ≥ 18 h (OR: 2.39, 95%CI: 1.35–4.23, P = 0.003) and maternal autoimmune diseases (OR: 5.30, 95%CI: 2.15–13.07, P < 0.001) were independent risk factors for CRP ≥ 8 mg/L. Cesarean delivery (OR 0.40, 95%CI: 0.26–0.60, P < 0.001) was independent protective factor for CRP ≥ 8 mg/L. (2) Threshold effect analysis: A non-linear relationship was found between GA and CRP. When GA is less than 33.9 weeks, the risk of CRP ≥ 8 mg/L was reduced by 28% with one week increased (P < 0.001), and when GA is more than 33.9 weeks, the risk of CRP ≥ 8 mg/L was increased by 61% with one week increased (P < 0.001).

Conclusions

GA, PROM, maternal autoimmune diseases and cesarean delivery were all independent influences neonatal CRP ≥ 8 mg/L on admission, and there was a nonlinear relationship between GA and neonatal CRP ≥ 8 mg/L on admission.
Prevalence and determinants of post-traumatic stress disorder five months after the 2019 huge flooding in Iran
Authors: Shabani Amir , Rasoulian Maryam , Naserbakht Morteza , Hakim Shooshtari Mitra , Hajebi Ahmad , Tiyuri Amir , Motevalian Seyed Abbas
Published: February 2024

Background

Despite the high occurrence of floods in Iran, its psychological consequences have been less discussed. The present paper addresses the prevalence of Post-traumatic Stress Disorder (PTSD) and its determinants among the affected adults by the huge flood of 2019.

Methods

An analytical cross-sectional study was conducted through household face-to-face surveys in August and September 2019. Individuals who were affected by floods and were at least 16 years old were randomly selected from three provinces in Iran: Lorestan and Khuzestan in the west and southwest, and Golestan in the northeast. The questionnaire of demographic and flood related variables in addition to the Impact of Event Scale-Revised (IES-R) were utilized to collect the data. We applied a complex sample analysis to describe the prevalence of PTSD and logistic regression analyses to find its determinants.

Results

Out of the 2,305 individuals approached for surveys, 1,671 (72.5%) adults affected by the floods participated in the study. The majority of participants were housewives, married, had either no formal education or primary education, and resided in rural areas. The prevalence of PTSD in the participants was 24.8% (CI 95%: 20.7–28.8%) and was significantly higher in Lorestan province (39.7%, P < 0.001). Determinants of PTSD, were unemployment (adjusted odds ratio [AOR] = 3.53, CI 95%: 1.38-9.00), primary (AOR = 2.44, CI 95%: 1.10–5.41) or high school (AOR = 2.35, CI 95%: 1.25–4.40) education (vs. university), a history of mental disorders (AOR = 2.36, CI 95%: 1.22–4.58), high damage to assets (AOR = 2.29, CI 95%: 1.40–3.75), limited access to health care services after the flood (AOR = 1.95, CI 95%: 1.20–3.19), not receiving compensation for flood damage (AOR = 1.94, CI 95%: 1.01–3.83), high wealth index (AOR = 1.90, CI 95%: 1.23–2.93), and flooded house with a height of more than one meter (AOR = 1.66, CI 95%: 1.02–2.76).

Conclusion

Results show a notable prevalence of PTSD, especially in Lorestan province, among adults affected by floods. Determinants of PTSD include unemployment, lower education, psychiatric history, extensive property damage, limited post-flood healthcare access, lack of compensation, and increased flood exposure. We recommend adopting an inclusive screening approach for high-risk groups and developing appropriate therapeutic and supportive interventions.
Unraveling the mediation role of frailty and depression in the relationship between social support and self-management among Chinese elderly COPD patients: a cross-sectional study
Authors: Zhao Jie , Zhang Xiaona , Li Xindan , Zhang Rui , Chang Yan , Li Yongju , Lu Hongyan
Published: February 2024

Background

Self-management (SM) is the key factor in controlling the progression of chronic obstructive pulmonary disease (COPD). Previous studies have reported that majority of COPD patients later presented with frailty and mental health diseases, which affect self-management. This study attempted to explore the mediation role of depression and frailty between social support and self-management in elderly COPD population.

Methods

Six hundred twenty-seven stable elderly COPD patients admitted to 5 public hospitals in Ningxia, China were selected as study subjects by convenience sampling method. Self-management, frailty, depression and social support were assessed using the COPD Self-management Scale (COPD-SMS), Frail Scale (FS), 15-item Geriatric Depression Scale (GDS-15), and Social Support Rating Scale (SSRS) respectively. The Pearson correlation analysis was used to assess the correlation between variables. Additionally, SPSS25.0 PROCESS plugin Model 6 was used to explore the mediating effects of frailty and depression in the relationship between social support and self-management.

Results

The mean participant age was 72.87 ± 7.03 years, 60.4% of participants were male. The mean total score of the COPD-SMS was 156.99 ± 25.15. Scores for the SSRS, FS, and GDS-15 were significantly correlated with COPD-SMS (p < 0.05). The analysis of the mediation effect demonstrated that social support has a direct predictive effect on self- management (β = 1.687, 95%CI: 1.359 to 2.318). Additionally, social support can also predict self- management indirectly through the mediation of depression (β = 0.290, 95%CI: 0.161 to 0.436) and frailty-depression (β = 0.040, 95%CI: 0.010 to 0.081). However, the mediation effect of frailty alone was not found to be statistically significant (β =—0.010, 95%CI: -0.061 to 0.036). The direct effect accounted for 84.06% of the total effect, while the indirect effect accounted for 15.94% of the total effect.

Conclusion

Self-management among elderly COPD patients was relatively moderate to low. Furthermore, frailty and depression were found to have a partially mediation role in the relationship between social support and self-management. Therefore, healthcare professionals need to comprehensively consider the frailty and depression status of patients, and implement targeted intervention measures as part of their care, which can improve the self-management of elderly COPD patients.
The effect of various therapeutic exercises on forward head posture, rounded shoulder, and hyperkyphosis among people with upper crossed syndrome: a systematic review and meta-analysis
Authors: Sepehri Simin , Sheikhhoseini Rahman , Piri Hashem , Sayyadi Parisa
Published: February 2024

Objectives

This review study aimed to evaluate the impact of therapeutic exercises on Upper-Crossed Syndrome (UCS). The study utilized a systematic review and meta-analysis approach to investigate the effects of various therapeutic exercises on forward head posture, rounded shoulders, and hyperkyphosis associated with upper crossed syndrome.

Methods

The study identified relevant keywords for each independent and dependent variable and conducted a search in scientific databases, including PubMed, Web of Science, Scopus, and Google Scholar, without any time limitations until 12 August 2023. Overall, 4625 articles were found in the selected databases, which were reduced to 1085 after being entered into the EndNote software and removing duplicate data. The full texts of 30 remaining studies were reviewed; ten articles meeting the criteria were included. Additionally, 12 studies from the Google Scholar database were included, resulting in 22 studies. Using Comprehensive meta-analysis software (CMA ver 3), data heterogeneity was measured with I2 and the Q tests. The Funnel Plot and Egger test methods were utilized to determine the possibility of publication bias. The JBI checklist was used to assess the quality of the studies.

Results

The results of the meta-analysis showed that therapeutic exercises were effective in improving forward head, rounded shoulders, and thoracic kyphosis angles (CI 95% = -1.85–1.161, P = 0.001, P = 0.001, CI95%=-1.822–1.15, and P = 0.001, CI 95%= -1.83–1.09, respectively).

Conclusion

Based on the results, it appears that performing therapeutic exercises in the form of strength exercises, stretching, shoulder-based exercises, and incredibly comprehensive exercises that target all muscles may be effective in reducing forward head, rounded shoulders, thoracic kyphosis, and overall UCS.

Level of evidence

1
Hexaxial external fixator versus intramedullary nail in treating segmental tibial fractures: a retrospective study
Authors: Zhao Zhiming , Shu Hengsheng , Jia Peng , Chen Xu , Guo Feng , Liu Yabin , Shi Bowen , Ji Guoqi , Cai Chengkuo , Shen Yidong
Published: February 2024

Background

It’s difficult to treat segmental tibial fractures (STFs), which are intricate injuries associated with significant soft tissue damage. The aim of this study was to compare the clinical effect of hexaxial external fixator (HEF) and intramedullary nail (IMN) in treatment of STFs.

Methods

A total of 42 patients with STFs were finally recruited between January 2018 and June 2022. There were 25 males and 17 females with age range of 20 to 60 years. All fractures were classified as type 42C2 using the Arbeitsgemeinschaftfür Osteosythese/Orthopaedic Trauma Association (AO/OTA) classification. 22 patients were treated with HEF and 20 patients were treated with IMN. The condition of vascular and neural injuries, time of full weight bearing, bone union time and infection rate were documented and analyzed between the two groups. The mechanical medial proximal tibial angle (mMPTA), mechanical posterior proximal tibial angle (mPPTA), mechanical lateral distal tibial angle (mLDTA), mechanical anterior distal tibial angle (mADTA), hospital for special surgery (HSS) knee joint score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle joint score, range of motion (ROM) of flexion of keen joint and ROM of plantar flexion and dorsal flexion of ankle joint were compared between the two groups at the last clinical visit.

Results

There were no vascular and neural injuries or other severe complications in both groups. All 22 patients in HEF group underwent closed reduction but 3 patients in IMN group were treated by open reduction. The time of full weight bearing was (11.3 ± 3.2) days in HEF group and (67.8 ± 5.8) days in IMN group(P < 0.05), with bone union time for (6.9 ± 0.8) months and (7.7 ± 1.4) months, respectively(P < 0.05). There was no deep infection in both groups. In the HEF group and IMN group, mMPTA was (86.9 ± 1.5)° and (89.7 ± 1.8)°(P < 0.05), mPPTA was (80.8 ± 1.9)° and (78.6 ± 2.0)°(P < 0.05), mLDTA was (88.5 ± 1.7)° and (90.3 ± 1.7)°(P < 0.05), while mADTA was (80.8 ± 1.5)° and (78.4 ± 1.3)°(P < 0.05). No significant differences were found between the two groups at the last clinical visit concerning HSS knee joint score and AOFAS ankle joint score, ROM of flexion of keen joint and ROM of plantar flexion of ankle joint (P > 0.05). The ROM of dorsal flexion of ankle joint in IMN group was (30.4 ± 3.5)°, better than (21.6 ± 2.8)° in HEF group (P < 0.05).

Conclusion

In terms of final clinical outcomes, the use of either HEF or IMN for STFs can achieve good therapeutic effects. While HEF is superior to IMN in terms of completely closed reduction, early full weight bearing, early bone union and alignment. Nevertheless, HEF has a greater impact on the ROM of dorsal flexion of the ankle joint, and much more care and adjustment are needed for the patients than IMN.
Enhancing deep learning classification performance of tongue lesions in imbalanced data: mosaic-based soft labeling with curriculum learning
Authors: Lee Sung-Jae , Oh Hyun Jun , Son Young-Don , Kim Jong-Hoon , Kwon Ik-Jae , Kim Bongju , Lee Jong-Ho , Kim Hang-Keun
Published: February 2024

Background

Oral potentially malignant disorders (OPMDs) are associated with an increased risk of cancer of the oral cavity including the tongue. The early detection of oral cavity cancers and OPMDs is critical for reducing cancer-specific morbidity and mortality. Recently, there have been studies to apply the rapidly advancing technology of deep learning for diagnosing oral cavity cancer and OPMDs. However, several challenging issues such as class imbalance must be resolved to effectively train a deep learning model for medical imaging classification tasks. The aim of this study is to evaluate a new technique of artificial intelligence to improve the classification performance in an imbalanced tongue lesion dataset.

Methods

A total of 1,810 tongue images were used for the classification. The class-imbalanced dataset consisted of 372 instances of cancer, 141 instances of OPMDs, and 1,297 instances of noncancerous lesions. The EfficientNet model was used as the feature extraction model for classification. Mosaic data augmentation, soft labeling, and curriculum learning (CL) were employed to improve the classification performance of the convolutional neural network.

Results

Utilizing a mosaic-augmented dataset in conjunction with CL, the final model achieved an accuracy rate of 0.9444, surpassing conventional oversampling and weight balancing methods. The relative precision improvement rate for the minority class OPMD was 21.2%, while the relative$${F}_{1}$$F1score improvement rate of OPMD was 4.9%.

Conclusions

The present study demonstrates that the integration of mosaic-based soft labeling and curriculum learning improves the classification performance of tongue lesions compared to previous methods, establishing a foundation for future research on effectively learning from imbalanced data.
Physical, oral, and swallowing functions of three patients with type A xeroderma pigmentosum: a report of three cases
Authors: Tamura Atsuko , Yamaguchi Kohei , Yanagida Ryosuke , Miyata Rie , Tohara Haruka
Published: February 2024

Background

Xeroderma pigmentosum (XP) is an extremely rare and severe form of photosensitivity. It is classified into types A–G or V according to the gene responsible for the disease. The progression and severity of symptoms vary depending on the type. Although dysphagia caused by decreased swallowing function and dental malposition due to stenosis of the dentition in the facial and oral regions is common, it has not been reported in detail. We report three cases of type A XP, in which central and peripheral neurological symptoms appeared early on and progressed rapidly. We describe the oral function of these patients, focusing on the swallowing function and dentition malposition.

Case presentation

Two males (27 and 25 years old) and one female (28 years old) presented with diverse neurological symptoms. We focused on the relationship between the changes in swallowing and oral functions and conditions due to decline in physical function. Some effects were observed by addressing the decline in swallowing and oral functions. In particular, a dental approach to manage the narrowing of the dentition, which was observed in all three patients, improved the swallowing and oral functions and maintained the current status of these functions.

Conclusions

In type A XP, early decline in oral and swallowing functions is caused by the early decline in physical function, and it is necessary to monitor the condition at an early stage.
Influence of sociodemographic and obstetric factors on maternal mortality in Brazil from 2011 to 2021
Authors: Lima Figueiredo Eric Renato , do Socorro Carvalho Miranda Claudia , Viana Campos Ana Cristina , de Campos Gomes Fabiana , Câmara Rodrigues Cibele Nazaré , de Melo-Neto João Simão
Published: February 2024

Background

Obstetric causes are classified as direct (complications of pregnancy, childbirth or the puerperium) or indirect (caused by pregnancy but not directly caused by it). This study aimed to analyze maternal mortality from obstetric causes in Brazil from 2011 to 2021.

Methods

This was an ecological study on mortality and live births. The outcomes were the specific risk of mortality from direct and indirect cause adjustment and death during pregnancy and the puerperium. Binary and multiple linear logistic regressions were used to assess the influence of sociodemographic factors and maternal and child health indicators on maternal mortality and time of death (pregnancy and puerperium).

Results

Regarding mortality during pregnancy and during the puerperium, increased (p = 0.003) and decreased (p = 0.004) mortality over the years, respectively; residing in the northern region was associated with lower (p < 0.05) and greater (p = 0.035) odds; and the Maternal Mortality Committee was the primary and least active source of investigation, respectively (p < 0.0001). The number of deaths from indirect causes increased with age (p < 0.001) and in the northern region (p = 0.011) and decreased in the white (< 0.05) and stable union (0.002) regions. Specifically, for mortality risk, the age group [women aged 15–19 years presented an increase in cesarean section (p < 0.001) was greater than that of women who had < 4 antenatal visits (p < 0.001)], education [women who completed high school (8 to 11 years) was greater when they had < 4 prenatal visits (p = 0.018)], and marital status [unmarried women had more than 4 antenatal visits (p < 0.001); cesarean birth (p = 0.010) and < 4 antenatal visits (p = 0.009) were predictors of marriage; and women in a stable union who had < 4 prenatal visits and live births to teenage mothers (p < 0.001) were predictors]. Women who had no education (p = 0.003), were divorced (p = 0.036), had cesarean deliveries (p < 0.012), or lived in the north or northeast (p < 0.008) had higher indirect specific mortality risk.

Conclusions

Sociodemographic factors and maternal and child health indicators were related to different patterns of obstetric mortality. Obstetric mortality varied by region, marital status, race, delivery, prenatal care, and cause of death.
Enhancing proficiency in ascites puncture through procedural simulation: an audit type study investigating medium-term skill retention
Authors: Hammami Aya , Ghali Hela , Elleuch Nour , Ben Saad Omar Khalil , Jaziri Hanen , Ksiaa Mehdi , Ali Habiba Sik
Published: February 2024

Introduction

Medical simulation has become an essential teaching method for all health professionals. It not only allows to acquire technical and non-technical knowledge, but also helps the maintenance of acquired knowledge in the medium and long term. Ascites puncture is part of the basic technical procedures learned by medical students during their internship.

Objectives

To evaluate the role of simulation-based learning of ascites puncture on the improvement of theoretical knowledge and maintenance of skills at 3 months.

Methods

We conducted an audit type study with two cycles of data collection at the simulation center at the Faculty of Medicine of Sousse between November 2020 and June 2021. We included learners in their third year of medical studies who had a hospital internship in the gastroenterology department at Sahloul Hospital in Sousse. All learners attended the initial simulation session on ascites fluid puncture. Thereafter, they were free to accept or refuse participation in the evaluation session that was scheduled after 3 months, depending on their availability.

Results

Forty learners participated in the procedural simulation of the ascites fluid puncture technique. Thirty-four (85%) were female and six (5%) were male. In our study, we showed that following procedural simulation training of ascites puncture, there was a significant improvement in the theoretical knowledge of the learners (p < 0.000). Objective assessment of technical skills after 3 months showed the benefit of performance maintenance (p < 0.000).

Conclusion

Our study confirmed the benefit of simulation-based learning on the improvement of theoretical knowledge and the maintenance of technical performance in the medium term.
A national program to advance dementia research in Vietnam
Authors: Vu Huyen Thi Thanh , Nguyen Tuan Anh , Nguyen Thu Thi Hoai , Nguyen Anh Trung , Tran Duyen , Nguyen Huong , Hinton Ladson , Pham Thang
Published: February 2024

Background

As Vietnam and other low- and middle-income countries (LMIC) experience a rapid increase in the number of people living with dementia, an acute need exists to strengthen research capacity to inform policy, improve care and support, and develop national dementia plans. We describe the development and early outcomes of an National Institutes of Health (NIH)/National Institute on Aging (NIA)-funded national dementia research capacity building program in Vietnam.

Methods

The research capacity building program commenced in 2019 and has three components: (1) Vietnam Alzheimer’s and other dementias research Network (VAN), (2) a mentored pilot grant program, and (3) research training, networking, and dissemination activities. The pilot grant program funds Vietnamese researchers for one to two years to conduct research focusing on Alzheimer’s Disease and Alzheimer’s Disease Related Dementias (AD/ADRD). Grants are reviewed and scored using NIH criteria, and priority is given to pilot grants with policy relevance and potential for future funding. An international pool of high-income country (e.g., United States, Australia, and United Kingdom) mentors has been engaged and mentors paired with each funded project. Training and networking activities include workshops on AD/ADRD research topics and regular meetings in conjunction with Vietnam’s annual national dementia/geriatric conferences. Dissemination is facilitated through targeted outreach and the creation of a national network of institutions.

Results

Over four years (2019–2023), we received 62 applications, reviewed 58 applications, and funded 21 projects (4–5 per year). Funded investigators were from diverse disciplines and institutions across Vietnam with projects on a range of topics, including biomarkers, prevention, diagnosis, neuropsychological assessment, family caregiver support, dementia education, and clinical trials. A network of 12 leading academic and research institutions nationwide has been created to facilitate dissemination. Six research training workshops have been organized and included presentations from international speakers. Grantees have published or presented their studies at both national and international levels. The mentoring program has helped grantees to build their research skills and expand their research network.

Conclusion

This research capacity building program is the first of its kind in Vietnam and may serve as a useful model for other LMIC.
The coinfection of ALVs causes severe pathogenicity in Three-Yellow chickens
Authors: Wang Peikun , Wang Jing , Wang Na , Xue Cong , Han Zhaoqing
Published: February 2024

The coinfection of ALVs (ALV-J plus ALV-A or/and ALV-B) has played an important role in the incidence of tumors recently found in China in local breeds of yellow chickens. The study aims to obtain a better knowledge of the function and relevance of ALV coinfection in the clinical disease of avian leukosis, as well as its unique effect on the pathogenicity in Three-yellow chickens. One-day-old Three-yellow chicks (one day old) were infected with ALV-A, ALV-B, and ALV-J mono-infections, as well as ALV-A + J, ALV-B + J, and ALV-A + B + J coinfections, via intraperitoneal injection, and the chicks were then grown in isolators until they were 15 weeks old. The parameters, including the suppression of body weight gain, immune organ weight, viremia, histopathological changes and tumor incidence, were observed and compared with those of the uninfected control birds. The results demonstrated that coinfection with ALVs could induce more serious suppression of body weight gain (P < 0.05), damage to immune organs (P < 0.05) and higher tumor incidences than monoinfection, with triple infection producing the highest pathogenicity. The emergence of visible tumors and viremia occurred faster in the coinfected birds than in the monoinfected birds. These findings demonstrated that ALV coinfection resulted in considerably severe pathogenic and immunosuppressive consequences.
Efficient production of 2′-fucosyllactose from fructose through metabolically engineered recombinant Escherichia coli
Authors: You Ran , Wang Lei , Hu Meirong , Tao Yong
Published: February 2024

Background

The biosynthesis of human milk oligosaccharides (HMOs) using several microbial systems has garnered considerable interest for their value in pharmaceutics and food industries. 2′-Fucosyllactose (2′-FL), the most abundant oligosaccharide in HMOs, is usually produced using chemical synthesis with a complex and toxic process. Recombinant E. coli strains have been constructed by metabolic engineering strategies to produce 2′-FL, but the low stoichiometric yields (2′-FL/glucose or glycerol) are still far from meeting the requirements of industrial production. The sufficient carbon flux for 2′-FL biosynthesis is a major challenge. As such, it is of great significance for the construction of recombinant strains with a high stoichiometric yield.

Results

In the present study, we designed a 2′-FL biosynthesis pathway from fructose with a theoretical stoichiometric yield of 0.5 mol 2′-FL/mol fructose. The biosynthesis of 2′-FL involves five key enzymes: phosphomannomutase (ManB), mannose-1-phosphate guanylytransferase (ManC), GDP-d-mannose 4,6-dehydratase (Gmd), and GDP-l-fucose synthase (WcaG), and α-1,2-fucosyltransferase (FucT). Based on starting strain SG104, we constructed a series of metabolically engineered E. coli strains by deleting the key genes pfkA, pfkB and pgi, and replacing the original promoter of lacY. The co-expression systems for ManB, ManC, Gmd, WcaG, and FucT were optimized, and nine FucT enzymes were screened to improve the stoichiometric yields of 2′-FL. Furthermore, the gene gapA was regulated to further enhance 2′-FL production, and the highest stoichiometric yield (0.498 mol 2′-FL/mol fructose) was achieved by using recombinant strain RFL38 (SG104ΔpfkAΔpfkBΔpgi119-lacYΔwcaF::119-gmd-wcaG-manC-manB, 119-AGGAGGAGG-gapA, harboring plasmid P30). In the scaled-up reaction, 41.6 g/L (85.2 mM) 2′-FL was produced by a fed-batch bioconversion, corresponding to a stoichiometric yield of 0.482 mol 2′-FL/mol fructose and 0.986 mol 2′-FL/mol lactose.

Conclusions

The biosynthesis of 2′-FL using recombinant E. coli from fructose was optimized by metabolic engineering strategies. This is the first time to realize the biological production of 2′-FL production from fructose with high stoichiometric yields. This study also provides an important reference to obtain a suitable distribution of carbon flux between 2′-FL synthesis and glycolysis.
Ginseng-derived nanoparticles alleviate inflammatory bowel disease via the TLR4/MAPK and p62/Nrf2/Keap1 pathways
Authors: Yang Song , Li Wenjing , Bai Xueyuan , Di Nunzio Giada , Fan Liangliang , Zhao Yueming , Ren Limei , Zhao Ronghua , Bian Shuai , Liu Meichen , Wei Yuchi , Zhao Daqing , Wang Jiawen
Published: February 2024

Inflammatory bowel disease (IBD) is closely linked to the homeostasis of the intestinal environment, and exosomes can be used to treat IBD due to their high biocompatibility and ability to be effectively absorbed by the intestinal tract. However, Ginseng-derived nanoparticles (GDNPs) have not been studied in this context and their mechanism of action remains unclear. Here, we investigated GDNPs ability to mediate intercellular communication in a complex inflammatory microenvironment in order to treat IBD. We found that GDNPs scavenge reactive oxygen species from immune cells and intestinal epithelial cells, inhibit the expression of pro-inflammatory factors, promote the proliferation and differentiation of intestinal stem cells, as well as enhancing the diversity of the intestinal flora. GDNPs significantly stabilise the intestinal barrier thereby promoting tissue repair. Overall, we proved that GDNPs can ameliorate inflammation and oxidative stress in vivo and in vitro, acting on the TLR4/MAPK and p62/Keap1/Nrf2 pathways, and exerting an anti-inflammatory and antioxidant effect. GDNPs mitigated IBD in mice by reducing inflammatory factors and improving the intestinal environment. This study offers new evidence of the potential therapeutic effects of GDNPs in the context of IBD, providing the conceptual ground for an alternative therapeutic strategy.

Graphical Abstract
T-type voltage-gated channels, Na+/Ca2+-exchanger, and calpain-2 promote photoreceptor cell death in inherited retinal degeneration
Authors: Yan Jie , Wang Lan , Yang Qian-Lu , Yang Qian-Xi , He Xinyi , Dong Yujie , Hu Zhulin , Seeliger Mathias W. , Jiao Kangwei , Paquet-Durand François
Published: February 2024

Inherited retinal degenerations (IRDs) are a group of untreatable and commonly blinding diseases characterized by progressive photoreceptor loss. IRD pathology has been linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na+- and Ca2+-influx, subsequent activation of voltage-gated Ca2+-channels (VGCC), and further Ca2+ influx. However, a connection between excessive Ca2+ influx and photoreceptor loss has yet to be proven.

Here, we used whole-retina and single-cell RNA-sequencing to compare gene expression between the rd1 mouse model for IRD and wild-type (wt) mice. Differentially expressed genes indicated links to several Ca2+-signalling related pathways. To explore these, rd1 and wt organotypic retinal explant cultures were treated with the intracellular Ca2+-chelator BAPTA-AM or inhibitors of different Ca2+-permeable channels, including CNGC, L-type VGCC, T-type VGCC, Ca2+-release-activated channel (CRAC), and Na+/Ca2+ exchanger (NCX). Moreover, we employed the novel compound NA-184 to selectively inhibit the Ca2+-dependent protease calpain-2. Effects on the retinal activity of poly(ADP-ribose) polymerase (PARP), sirtuin-type histone-deacetylase, calpains, as well as on activation of calpain-1, and − 2 were monitored, cell death was assessed via the TUNEL assay.

While rd1 photoreceptor cell death was reduced by BAPTA-AM, Ca2+-channel blockers had divergent effects: While inhibition of T-type VGCC and NCX promoted survival, blocking CNGCs and CRACs did not. The treatment-related activity patterns of calpains and PARPs corresponded to the extent of cell death. Remarkably, sirtuin activity and calpain-1 activation were linked to photoreceptor protection, while calpain-2 activity was related to degeneration. In support of this finding, the calpain-2 inhibitor NA-184 protected rd1 photoreceptors.

These results suggest that Ca2+ overload in rd1 photoreceptors may be triggered by T-type VGCCs and NCX. High Ca2+-levels likely suppress protective activity of calpain-1 and promote retinal degeneration via activation of calpain-2. Overall, our study details the complexity of Ca2+-signalling in photoreceptors and emphasizes the importance of targeting degenerative processes specifically to achieve a therapeutic benefit for IRDs.
Design of stable circular permutants of the GroEL chaperone apical domain
Authors: Melnik Tatiana N. , Majorina Maria A. , Vorobeva Daria E. , Nagibina Galina S. , Veselova Victoria R. , Glukhova Ksenia A. , Pak Marina A. , Ivankov Dmitry N. , Uversky Vladimir N. , Melnik Bogdan S.
Published: February 2024

Enhancing protein stability holds paramount significance in biotechnology, therapeutics, and the food industry. Circular permutations offer a distinctive avenue for manipulating protein stability while keeping intra-protein interactions intact. Amidst the creation of circular permutants, determining the optimal placement of the new N- and C-termini stands as a pivotal, albeit largely unexplored, endeavor. In this study, we employed PONDR-FIT’s predictions of disorder propensity to guide the design of circular permutants for the GroEL apical domain (residues 191–345). Our underlying hypothesis posited that a higher predicted disorder value would correspond to reduced stability in the circular permutants, owing to the increased likelihood of fluctuations in the novel N- and C-termini. To substantiate this hypothesis, we engineered six circular permutants, positioning glycines within the loops as locations for the new N- and C-termini. We demonstrated the validity of our hypothesis along the set of the designed circular permutants, as supported by measurements of melting temperatures by circular dichroism and differential scanning microcalorimetry. Consequently, we propose a novel computational methodology that rationalizes the design of circular permutants with projected stability.
Mitochondrial dynamics and colorectal cancer biology: mechanisms and potential targets
Authors: Wu Zihong , Xiao Chong , Long Jing , Huang Wenbo , You Fengming , Li Xueke
Published: February 2024

Colorectal cancer (CRC) is a significant public health concern, and its development is associated with mitochondrial dysfunction. Mitochondria can adapt to the high metabolic demands of cancer cells owing to their plasticity and dynamic nature. The fusion–fission dynamics of mitochondria play a crucial role in signal transduction and metabolic functions of CRC cells. Enhanced mitochondrial fission promotes the metabolic reprogramming of CRC cells, leading to cell proliferation, metastasis, and chemoresistance. Excessive fission can also trigger mitochondria-mediated apoptosis. In contrast, excessive mitochondrial fusion leads to adenosine triphosphate (ATP) overproduction and abnormal tumor proliferation, whereas moderate fusion protects intestinal epithelial cells from oxidative stress-induced mitochondrial damage, thus preventing colitis-associated cancer (CAC). Therefore, an imbalance in mitochondrial dynamics can either promote or inhibit CRC progression. This review provides an overview of the mechanism underlying mitochondrial fusion–fission dynamics and their impact on CRC biology. This revealed the dual role of mitochondrial fusion–fission dynamics in CRC development and identified potential drug targets. Additionally, this study partially explored mitochondrial dynamics in immune and vascular endothelial cells in the tumor microenvironment, suggesting promising prospects for targeting key fusion/fission effector proteins against CRC.

Graphical Abstract
Differences in spatial niche of terrestrial mammals when facing extreme snowfall: the case in east Asian forests
Authors: Enari Hiroto , Enari Haruka S. , Sekiguchi Tatsuhito , Tanaka Motohisa , Suzuki Sohsuke
Published: February 2024

Background

Recent climate changes have produced extreme climate events. This study focused on extreme snowfall and intended to discuss the vulnerability of temperate mammals against it through interspecies comparisons of spatial niches in northern Japan. We constructed niche models for seven non-hibernating species through wide-scaled snow tracking on skis, whose total survey length was 1144 km.

Results

We detected a low correlation (rs < 0.4) between most pairs of species niches, indicating that most species possessed different overwintering tactics. A morphological advantage in locomotion cost on snow did not always expand niche breadth. In contrast, a spatial niche could respond to (1) drastic landscape change by a diminishing understory due to snow, possibly leading to changes in predator-prey interactions, and (2) the mass of cold air, affecting thermoregulatory cost and food accessibility. When extraordinary snowfall occurred, the nonarboreal species with larger body sizes could niche shift, whereas the smaller-sized or semi-arboreal mammals did not. In addition, compared to omnivores, herbivores were prone to severe restriction of niche breadth due to a reduction in food accessibility under extreme climates.

Conclusions

Dietary habits and body size could determine the redundancy of niche width, which may govern robustness/vulnerability to extreme snowfall events.
Using near-infrared spectroscopy to predict nitrogen and phosphorus concentrations of herbarium specimens under different storage conditions
Authors: Kühn Paul , Proß Tobias , Römermann Christine , Wesche Karsten , Bruelheide Helge
Published: February 2024

Background

Herbaria are becoming increasingly important as archives of biodiversity, and play a central role in taxonomic and biogeographic studies. There is also an ongoing interest in functional traits and the way they mediate interactions between a plant species and its environment. Herbarium specimens allow tracking trait values over time, and thus, capturing consequences of anthropogenic activities such as eutrophication. Here, we present an open, reproducible, non-destructive workflow to collect leaf trait data from herbarium specimens using near-infrared spectroscopy (NIRS), and a proof of concept for the reliability of this approach.

Results

We carried out three experiments to test the suitability of non-destructive NIRS methods to predict leaf traits both for fresh and dried leaves: (1) With a fertilization experiment, we studied whether NIRS was able to capture changes in leaf N and leaf P during a fertilization experiment and we compared contents predicted by NIRS with results obtained from regular wet lab methods. Calibration models for leaf nitrogen and phosphorus contents had a quality of R2 = 0.7 and 0.5, respectively. We fitted calibration models for NIRS readings on fresh and dried leaf samples, both of which produced equally precise predictions compared to results from wet lab analyses. (2) We tested the effect of herbarium conservation on NIRS readings by simulating them through the application of six treatments combining freezing, drying and pesticide spraying in a factorial scheme and comparing these with untreated samples. No consistent changes were observed in the spectra quality before and after the simulated herbarium conditions. (3) Finally, we studied the effect of specimen storage duration using specimens from a 2018 study which were re-analyzed and compared with spectra obtained in 2021. No consistent changes in spectra were observed after the storage period.

Conclusions

The results demonstrate the reliability of NIRS to measure leaf N and P on herbarium samples. Together with the calibration method and dataset presented here, they provide a toolset allowing researchers to study the development of leaf traits and their response to environmental changes over decades and even centuries in a fast and non-destructive manner.
Relationship between polymorphisms and mutations at rs7125942 and rs3736228 of LRP5 gene and bone metabolism in postmenopausal women
Authors: Li Jun , Li Ya , Li Siyuan , Lu Yunqiu , Rai Partab
Published: February 2024

Objective

To analyze the relationship between the polymorphism and mutation of rs7125942 and rs3736228 locus in the low-density lipoprotein receptor-related protein 5 (LRP5) genotype and bone mineral density (BMD) in postmenopausal women in Xinjiang, China, to provide a basis for prevention and treatment of the disease.

Methods

According to the results of dual-energy X-ray (DEXA) determination of BMD, the 136 subjects were divided into three groups: Group A: normal bone mass, Group B: osteopenia, Group C: osteoporosis. 1. Age, body, mass index (BMI), and menopause of all subjects were recorded. 2. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and clinical biochemical data were determined. 3. LRP5 locus polymorphisms were determined by time-of-flight mass spectrometry.

Results

1. Compared with group A, the age, ALP, Cr, and BUN levels in group B and group C were increased, but UA levels were lower (P < 0.05), and Serum P was higher in the group C (P < 0.05). 2. There was no statistically significant difference in the prevalence of diabetes between the three groups (P > 0.05). 3. The ROC curves for different BMD sites such as L1, L2, L3, L4, L total, and femoral neck were 0.929, 0.955, 0.901, 0.914, 0.885, and 0.873 (P < 0.01). 4. At rs7125942 locus, there was statistically significant difference in the distribution of wild-type (CC) and mutant (CG) with the normal bone mass (NBM) group and the abnormal bone mass (ABM) group (P < 0.05). 5. At rs7125942 locus, compared with wild-type (CC), mutant (CG) had lower LDL and FPG in NBM group (P < 0.05), and lower serum ALP in the ABM group (P < 0.05). At rs3736228 locus, the BMD (Femoral neck) of mutant (CT/TT) was lower than that of wild-type (CC) in the NBM group (P < 0.05). 6. Age and menopausal years were negatively correlated with BMD of the femoral neck and L1-4 (P < 0.05), and BMI and TG were positively (P < 0.05), and the results of multiple linear regression analysis showed that age, BMI, and TG were both independent factors affecting BMD (P < 0.05).