bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat Stress During Gametogenesis Irreversibly Damages Female Reproductive Organ in Rice
Authors: Shi Wanju , Yang Juan , Kumar Ritesh , Zhang Xinzheng , Impa Somayanda M. , Xiao Gui , Jagadish S. V. Krishna
Published: June 2022

Heat stress during gametogenesis leads to spikelet sterility. To ascertain the role of female reproductive organ (pistil), two rice genotypes N22 and IR64 with contrasting heat stress responses were exposed to control (30 °C) and heat stress (38 °C and 40 °C) during megasporogenesis. Anatomical observations of ovule revealed greater disappearance of megaspore mother cell and nuclei at early stages, and during later stages mature embryo sac without female germ unit, improper positioning of nuclei, and shrunken embryo sac was observed in the sensitive IR64. Under heat stress, a decrease in sugar and starch, increase in H2O2 and malondialdehyde with lower antioxidant enzyme activities were recorded in pistils of both N22 and IR64. Lower accumulation of TCA cycle metabolites and amino acids were noticed in IR64 pistils under heat stress at gametogenesis, whereas N22 exhibited favorable metabolite profiles. At heading, however, N22 pistils had higher carbohydrate accumulation and better ROS homeostasis, suggesting higher recovery after heat stress exposure. In summary, the results indicate that heat stress during megasporogenesis leads to irreversible anatomical and physiological changes in pistil and alters metabolic signatures leading to increased spikelet sterility in rice. Mechanisms identified for enhanced heat tolerance in pistil can help in developing rice varieties that are better adapted to future hotter climate.
Subjective factors affecting prognosis of 469 patients with esophageal squamous cell carcinoma: a retrospective cohort study of endoscopic screening
Authors: Nakamura Jun , Manabe Noriaki , Yamatsuji Tomoki , Fujiwara Yoshinori , Murao Takahisa , Ayaki Maki , Fujita Minoru , Shiotani Akiko , Ueno Tomio , Monobe Yasumasa , Akiyama Takashi , Haruma Ken , Naomoto Yoshio , Hata Jiro
Published: June 2022

Background

To date, no in-depth studies have focused on the impact of various clinical characteristics of esophageal squamous cell carcinoma (ESCC), including its association with subjective symptoms, on patient prognosis. We aimed to investigate the clinical factors that affect the prognosis of patients with ESCC and to clarify how subjective symptoms are related to prognosis.

Methods

We retrospectively evaluated the clinical records of 503 consecutive patients with ESCC from April 2011 to December 2019. Six established prognostic factors for ESCC (body mass index, alcohol drinking, cigarette smoking, sex, clinical stage, and age) and subjective symptoms were used to subgroup patients and analyze survival differences. Next, the patients were divided into two groups: a symptomatic group and an asymptomatic group. In the symptomatic group, differences in the incidence of subjective symptoms according to tumor size, tumor location, macroscopic tumor type, and clinical stage were examined. Finally, subjective symptoms were divided into swallowing-related symptoms and other symptoms, and their prognosis was compared.

Results

Multivariate Cox regression analysis identified sex [hazard ratio (HR) 1.778; 95% CI 1.004–3.149; p = 0.049], TNM classification (HR 6.591; 95% CI 3.438–12.63; p < 0.001), and subjective symptoms (HR 1.986; 95% CI 1.037–3.803; p = 0.0386) as independent risk factors for overall survival. In the symptomatic group, the mean time from symptom onset to diagnosis was 2.4 ± 4.3 months. The incidence of subjective symptoms differed by clinical stage, and the prognosis of patients with swallowing-related symptoms was significantly worse than that of patients with other symptoms.

Conclusion

The results of this study suggest that screening by upper gastrointestinal endoscopy, independent of subjective symptoms (especially swallowing-related symptoms), may play an important role in the early detection and improvement of prognosis of ESCC, although further validation in a large prospective study is needed.
Equipment-free, unsupervised high intensity interval training elicits significant improvements in the physiological resilience of older adults
Authors: Sian Tanvir S , Inns Thomas B , Gates Amanda , Doleman Brett , Bass Joseph J , Atherton Philip J , Lund Jonathan N , Phillips Bethan E
Published: June 2022

Background

Reduced cardiorespiratory fitness (CRF) is an independent risk factor for dependency, cognitive impairment and premature mortality. High-intensity interval training (HIIT) is a proven time-efficient stimulus for improving both CRF and other facets of cardiometabolic health also known to decline with advancing age. However, the efficacy of equipment-free, unsupervised HIIT to improve the physiological resilience of older adults is not known.

Methods

Thirty independent, community-dwelling older adults (71(SD: 5) years) were randomised to 4 weeks (12 sessions) equipment-free, supervised (in the laboratory (L-HIIT)) or unsupervised (at home (H-HIIT)) HIIT, or a no-intervention control (CON). HIIT involved 5, 1-minute intervals of a bodyweight exercise each interspersed with 90-seconds recovery. CRF, exercise tolerance, blood pressure (BP), body composition, muscle architecture, circulating lipids and glucose tolerance were assessed at baseline and after the intervention period.

Results

When compared to the control group, both HIIT protocols improved the primary outcome of CRF ((via anaerobic threshold) mean difference, L-HIIT: +2.27, H-HIIT: +2.29, bothp < 0.01) in addition to exercise tolerance, systolic BP, total cholesterol, non-HDL cholesterol andm. vastus lateralispennation angle, to the same extent. There was no improvement in these parameters in CON. There was no change in diastolic BP, glucose tolerance, whole-body composition or HDL cholesterol in any of the groups.

Conclusions

This is the first study to show that short-term, time-efficient, equipment-free, HIIT is able to elicit improvements in the CRF of older adults irrespective of supervision status. Unsupervised HIIT may offer a novel approach to improve the physiological resilience of older adults, combating age-associated physiological decline, the rise of inactivity and the additional challenges currently posed by the COVID-19 pandemic.

Trial registration

This study was registered at clinicaltrials.gov and coded:NCT03473990.
Acute effects of whey protein, alone and mixed with other macronutrients, on blood pressure and heart rate in older men
Authors: Oberoi Avneet , Giezenaar Caroline , Lange Kylie , Jones Karen L. , Horowitz Michael , Chapman Ian , Soenen Stijn
Published: June 2022

Background

Caloric supplements are increasingly used by older people, aiming to increase their daily protein intake. These high caloric drinks, rich in glucose and whey-protein in particular, may result in potential harmful decreases in blood pressure (BP). The effect of ingesting whey-protein with glucose and fat on BP is unknown. It has also been assumed that the maximum fall in systolic blood pressure occurs within 2 h of a meal.

Methods

This study aimed to determine in older men, the effects of whey-protein, alone and mixed with other macronutrients, on systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) in older men for 3 h. Thirteen older men (age 75 ± 2yrs; body mass index (BMI) 25.6 ± 0.6 kg/m2) ingested a drink on separate study days: (i) 70 g whey-protein (P280); (ii) 14 g whey-protein, 28 g carbohydrate, 12.4 g fat (M280); (iii) 70 g whey-protein, 28 g carbohydrate, 12.4 g fat (M504); or (iv) a non-caloric control drink (C).

Results

SBP decreased after all three nutrient drinks compared to the C, with the greatest reduction after the M504 drink (P = 0.008). Maximal decreases in SBP (C: -14 ± 2 mmHg, P280: -22 ± 2 mmHg, M280: -22 ± 4 mmHg, M504: -24 ± 3 mmHg) occurred about 2 h after drink ingestion and this fall was sustained thereafter (120-180 min: P280 and M504 vs. C P < 0.05). Maximum DBP decreases and HR increases occurred after M504, with no differences between the effects of the P280 and M280 drinks.

Conclusions

The effects of whey-protein containing drinks to lower BP and increase HR appear to be primarily dependent on their energy content rather than macronutrient composition and may persist for at least 3 h after ingestion,. Pure whey-protein drinks may represent the best approach to maximize protein intake without increasing the potential for deleterious BP falls in older people.

Trial registration

ACTRN12614000846628, 14/03/2019.
Antenatal screening timeline and cutoff scores of the Edinburgh Postnatal Depression Scale for predicting postpartum depressive symptoms in healthy women: a prospective cohort study
Authors: Tanuma-Takahashi Akiko , Tanemoto Tomohiro , Nagata Chie , Yokomizo Ryo , Konishi Akiko , Takehara Kenji , Ishikawa Tetsuo , Yanaihara Nozomu , Samura Osamu , Okamoto Aikou
Published: June 2022

Background

It is worthwhile to identify women at risk of developing postpartum depression during pregnancy. This study aimed to determine the optimal time and cutoff score for antenatal screening for prediction of postpartum depressive symptoms (PDS) using the Edinburgh Postnatal Depression Scale (EPDS) and to identify risk factors for PDS.

Methods

The target population was healthy pregnant women receiving antenatal care at a university hospital in Tokyo, Japan. During the first, second, and third trimesters, 3–4 days postpartum, and one month postpartum, they were asked to take the Japanese version of the EPDS questionnaire. The primary outcome of the study was PDS, defined as an EPDS score ≥ 9 at one month postpartum. The area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of EPDS scores at each antenatal screening time were calculated.

Results

From 139 pregnant women, 129 were successfully followed up throughout the study. The number of women with an EPDS score ≥ 9 during the first, second, and third trimesters, 3–4 days postpartum, and one month postpartum were 6/126 (4.8%), 9/124 (7.3%), 5/117 (4.3%), 17/123 (13.8%), and 15/123 (12.2%), respectively. Screening during the second trimester had the highest AUC to predict PDS (0.89) among antenatal screenings. The optimal EPDS cutoff score during the second trimester was 4/5 (sensitivity: 85.7%; specificity: 77.1%; PPV: 33.3%; NPV: 97.6%). An EPDS score ≥ 5 during the second trimester (adjusted odds ratio [aOR]: 15.9; 95% confidence interval [95%CI]: 3.2–78.1) and a family history of mental illness (aOR: 4.5; 95%CI: 1.2–17.5) were significantly associated with PDS.

Conclusions

Our study suggests that the EPDS score at the second trimester with the cutoff value of 4/5 may be adequate for initial screening for prediction of PDS. Women with an EPDS score ≥ 5 at the second trimester require more elaborate follow-up.
Analysis of the risk of complications during pregnancy in pregnant women with assisted reproductive technology: a retrospective study using registry linkage from 2013 to 2018 in Shanghai, China
Authors: He Mulan , Sun Xiaoxi , Wang Chunfang , Sui Yilun
Published: June 2022

Background

To evaluate the differences in pregnancy outcomes between assisted reproductive technology (ART) patients and natural pregnant women in Shanghai, China in the past 6 years objectively. And to assess the feasibility of the research method of registry-database linkage in mainland China.

Methods

This retrospective study was conducted using registry-database linkage. A total of 8102 pregnancies with ART and 8096 parturients with spontaneous conception (SC) from 10 reproductive centers and 111 hospitals composed our retrospective study. The primary outcomes were the rates of obstetric complications (pregnancy-induced hypertention [PIH], gestational diabetes mellitus [GDM], placenta previa, mode of delivery, preterm birth [PTB], low birth weight [LBW], and macrosomia). The prenatal outcomes were compared between ART and SC parturients, frozen-thawed embryo transfer (FET) and fresh embryo transfer, and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). We calculated odds ratios (ORs) and 95% confidence intervals (CIs).

Results

The final matching rate of the target population was 92% by using registry linkage. ART resulted in a higher rate of multiple birth, PTB, LBW, cesarean section, placenta previa and GDM compared with SC in the singleton cohort. In ART patients, pregnant women with FET had a significantly higher risk of PIH than those with fresh embryo transfer (14.1% Vs 9.3%, AOR1.528, 95% CI 1.303–1.793), but there was no difference between IVF and ICSI. FET is also related to the severity of PIH.

Conclusions

ART increased the rate of complications during pregnancy, the risk and severity of PIH in patients with FET was higher than that in patients with fresh embryo transfer. The registry-database linkage study is an objective and feasible research method in mainland China.
Impact of early tumor shrinkage on quality of life in patients treated with first-line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: results of Phase II QUACK trial
Authors: Ooki Akira , Morita Satoshi , Tsuji Akihito , Iwamoto Shigeyoshi , Hara Hiroki , Tanioka Hiroaki , Satake Hironaga , Kataoka Masato , Kotaka Masahito , Kagawa Yoshinori , Nakamura Masato , Shingai Tatsushi , Ishikawa Masashi , Miyake Yasuhiro , Suto Takeshi , Hashiguchi Yojiro , Yabuno Taichi , Ando Masahiko , Sakamoto Junichi , Yamaguchi Kensei
Published: June 2022

Purpose

Although early tumor shrinkage (ETS) is a predictor of improved overall survival (OS), the association between ETS and health-related quality of life (HRQOL) remains unclear for patients with metastatic colorectal cancer (mCRC) treated with first-line cetuximab plus chemotherapy.

Methods

The data were collected from a prospective trial that assessed HRQOL using the EORTC QLQ-C30. The impact of ETS on HRQOL was estimated using a linear mixed-effects model for repeated measures.

Results

ETS was achieved in 82 (64.1%) of 128 mCRC patients treated with first-line cetuximab plus chemotherapy, and these patients had a significantly longer OS than those without ETS (HR, 0.38; 95% CI, 0.20–0.72; P = .002). Asymptomatic patients with ETS had a favorable OS, while symptomatic patients without ETS had a worse OS (2-year OS rates, 77.8% vs. 42.5%). Symptomatic patients with ETS had similar outcomes as asymptomatic patients without ETS (2-year OS rates, 64.1% vs. 67.0%). For symptomatic patients, ETS was associated with improved HRQOL scores between baseline and 8 weeks: the mean changes for patients with and without ETS were 5.86 and -4.94 for global health status (GHS)/QOL, 26.73 and 3.79 for physical functioning, and 13.58 and -3.10 for social functioning, respectively. The improved HRQOL was comparable to that of asymptomatic patients without ETS. For asymptomatic patients, ETS showed a decreased deterioration in HRQOL.

Conclusion

Our findings highlight the importance of ETS for HRQOL and prognostic estimates, and assessing ETS may provide clinically useful information for physicians and patients to make more informed decisions.
Real-life effectiveness of dupilumab in patients with mild to moderate bronchial asthma comorbid with CRSwNP
Authors: Minagawa Shunsuke , Araya Jun , Watanabe Naoaki , Fujimoto Shota , Watanabe Junko , Hara Hiromichi , Numata Takanori , Kuwano Kazuyoshi , Matsuwaki Yoshinori
Published: June 2022

Background

Dupilumab, an anti-IL-4α receptor antibody, is a new treatment for severe or refractory asthma. However, real-world evidence on the efficacy of dupilumab in patients with mild to moderate bronchial asthma is lacking.

Methods

We retrospectively evaluated the effects of dupilumab in 62 patients who received dupilumab for eosinophilic sinusitis comorbid with asthma at a single centre in Japan. Type 2 inflammatory markers, ACT, respiratory function tests, and forced oscillation technique (FOT) were analysed before, three months after, and one year after dupilumab administration, mainly in patients with mild to moderate asthma.

Results

FEV1, %FEV1, %FVC, treatment steps for asthma and ACT improved significantly after three months of dupilumab treatment. FeNO was markedly decreased, whereas IgE and eosinophil counts showed no significant changes. Pre- and post-treatment respiratory resistance (Rrs) and respiratory reactance (Xrs) correlated significantly with FEV1. Improvement in %FEV1 was associated with higher FeNO and higher serum IgE before dupilumab treatment.

Conclusion

Dupilumab treatment for sinusitis may improve respiratory functions, asthma symptoms, and asthma treatment reduction, even if the associated bronchial asthma is not severe.
Remote monitoring of cancer patients during the Covid-19 pandemic – an interview study of nurses’ and physicians’ experiences
Authors: Grøndahl Vigdis Abrahamsen , Helgesen Ann Karin , Holm Elisabet , Magnussen Jannik , Leonardsen Ann-Chatrin
Published: June 2022

Background

Due to the Covid-19 pandemic, remote monitoring of patients outside hospitals rapidly increased. Previous studies show that healthcare professionals’ competence in digitalization needs to be improved. Little is known about how Covid-19 has affected the use of remote monitoring of cancer patients. The purpose of the study was therefore to explore healthcare personnels’ experiences with remote monitoring of cancer patients during the Covid-19 pandemic. 

Methods

The study had an explorative and descriptive design using semi-structured individual interviews for data collection. Data was analyzed by content analysis.

Results

A total of ten healthcare personnel working in the cancer department and out-patient cancer clinic in the hospital participated; four physicians and six registered nurses. Two categories and four subcategories were identified: 1) «Maintaining personalized healthcare services» comprising the subcategories a) «Adjusting services to patients’ health condition» and b) «Ensuring continuity»; and 2) «A supplement, but not a replacement» comprising the subcategories a) «Impact on interpersonal relations» and b) «The importance of clinical assessment».

Conclusions

This study indicates that remote monitoring through telephone was preferred by both healthcare personnel and patients. The nurses and physicians experienced a more frequent contact with their patients, but emphasized the importance of physical meetings for building relationship, and for thorough clinical examination. Our findings indicate a need to facilitate a work environment where healthcare personnel can be fast learners in using digital tools to provide best possible healthcare quality. Moreover, it is imperative to develop a workplace suitable for the use of digital technology for remote monitoring, and to provide digital tools that is easy to use for both healthcare personnel and patients.
Lactobacillus plantarum 17–5 attenuates Escherichia coli-induced inflammatory responses via inhibiting the activation of the NF-κB and MAPK signalling pathways in bovine mammary epithelial cells
Authors: Li Ke , Yang Ming , Tian Mengyue , Jia Li , Du Jinliang , Wu Yinghao , Li Lianmin , Yuan Lining , Ma Yuzhong
Published: June 2022

Background

Mastitis is one of the most prevalent diseases and causes considerable economic losses in the dairy farming sector and dairy industry. Presently, antibiotic treatment is still the main method to control this disease, but it also brings bacterial resistance and drug residue problems.Lactobacillus plantarum(L. plantarum) is a multifunctional probiotic that exists widely in nature. Due to its anti-inflammatory potential,L. plantarumhas recently been widely researched in complementary therapies for various inflammatory diseases. In this study, the apoptotic ratio, the expression levels of various inflammatory mediators and key signalling pathway proteins inEscherichia coli-induced bovine mammary epithelial cells (BMECs) under different doses ofL. plantarum17–5 intervention were evaluated.

Results

The data showed thatL. plantarum17–5 reduced the apoptotic ratio, downregulated the mRNA expression levels ofTLR2,TLR4,MyD88,IL1β,IL6,IL8,TNFα,COX2,iNOS,CXCL2andCXCL10, and inhibited the activation of the NF-κB and MAPK signalling pathways by suppressing the phosphorylation levels of p65, IκBα, p38, ERK and JNK.

Conclusions

The results proved thatL. plantarum17–5 exerted alleviative effects inEscherichia coli-induced inflammatory responses of BMECs.
Oxaloacetate Treatment For Mental And Physical Fatigue In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID fatigue patients: a non-randomized controlled clinical trial
Authors: Cash Alan , Kaufman David Lyons
Published: June 2022

Background

There is no approved pharmaceutical intervention for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS). Fatigue in these patients can last for decades. Long COVID may continue to ME/CFS, and currently, it is estimated that up to 20 million Americans have significant symptoms after COVID, and the most common symptom is fatigue. Anhydrous Enol-Oxaloacetate, (AEO) a nutritional supplement, has been anecdotally reported to relieve physical and mental fatigue and is dimished in ME/CFS patients. Here, we examine the use of higher dosage AEO as a medical food to relieve pathological fatigue.

Methods

ME/CFS and Long-COVID patients were enrolled in an open label dose escalating “Proof of Concept” non-randomized controlled clinical trial with 500 mg AEO capsules. Control was provided by a historical ME/CFS fatigue trial and supporting meta-analysis study, which showed average improvement with oral placebo using the Chalder Scale of 5.9% improvement from baseline. At baseline, 73.7% of the ME/CFS patients were women, average age was 47 and length of ME/CFS from diagnosis was 8.9 years. The Long-COVID patients were a random group that responded to social media advertising (Face Book) with symptoms for at least 6 months. ME/CFS patients were given separate doses of 500 mg BID (N = 23), 1,000 mg BID (N = 29) and 1000 mg TID (N = 24) AEO for six weeks. Long COVID patients were given 500 mg AEO BID (N = 22) and 1000 mg AEO (N = 21), again over a six-week period. The main outcome measure was to compare baseline scoring with results at 6 weeks with the Chalder Fatigue Score (Likert Scoring) versus historical placebo. The hypothesis being tested was formulated prior to data collection.

Results

76 ME/CFS patients (73.7% women, median age of 47) showed an average reduction in fatigue at 6 weeks as measured by the “Chalder Fatigue Questionnaire” of 22.5% to 27.9% from baseline (P < 0.005) (Likert scoring). Both physical and mental fatigue were significantly improved over baseline and historical placebo. Fatigue amelioration in ME/CFS patients increased in a dose dependent manner from 21.7% for 500 mg BID to 27.6% for 1000 mg Oxaloacetate BID to 33.3% for 1000 mg TID. Long COVID patients’ fatigue was significantly reduced by up to 46.8% in 6-weeks.

Conclusions

Significant reductions in physical and metal fatigue for ME/CFS and Long-COVID patients were seen after 6 weeks of treatment. As there has been little progress in providing fatigue relief for the millions of ME/CFS and Long COVID patients, anhydrous enol oxaloacetate may bridge this important medical need. Further study of oxaloacetate supplementation for the treatment of ME/CFS and Long COVID is warranted.

Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04592354 Registered October 19, 2020.

Graphical Abstract
Using zebrafish to understand reciprocal interactions between the nervous and immune systems and the microbial world
Authors: Levraud Jean-Pierre , Rawls John F. , Clatworthy Anne E.
Published: June 2022

Animals rely heavily on their nervous and immune systems to perceive and survive within their environment. Despite the traditional view of the brain as an immunologically privileged organ, these two systems interact with major consequences. Furthermore, microorganisms within their environment are major sources of stimuli and can establish relationships with animal hosts that range from pathogenic to mutualistic. Research from a variety of human and experimental animal systems are revealing that reciprocal interactions between microbiota and the nervous and immune systems contribute significantly to normal development, homeostasis, and disease. The zebrafish has emerged as an outstanding model within which to interrogate these interactions due to facile genetic and microbial manipulation and optical transparency facilitating in vivo imaging. This review summarizes recent studies that have used the zebrafish for analysis of bidirectional control between the immune and nervous systems, the nervous system and the microbiota, and the microbiota and immune system in zebrafish during development that promotes homeostasis between these systems. We also describe how the zebrafish have contributed to our understanding of the interconnections between these systems during infection in fish and how perturbations may result in pathology.
Sparse logistic regression revealed the associations between HBV PreS quasispecies and hepatocellular carcinoma
Authors: Jia Jian-an , Zhang Shuqin , Bai Xin , Fang Meng , Chen Shipeng , Liang Xiaotao , Zhu Shanfeng , Wong Danny Ka-Ho , Zhang Anye , Feng Jianfeng , Sun Fengzhu , Gao Chunfang
Published: June 2022

Background

Chronic infection with hepatitis B virus (HBV) has been proved highly associated with the development of hepatocellular carcinoma (HCC).

Aims

The purpose of the study is to investigate the association between HBV preS region quasispecies and HCC development, as well as to develop HCC diagnosis model using HBV preS region quasispecies.

Methods

A total of 104 chronic hepatitis B (CHB) patients and 117 HBV-related HCC patients were enrolled. HBV preS region was sequenced using next generation sequencing (NGS) and the nucleotide entropy was calculated for quasispecies evaluation. Sparse logistic regression (SLR) was used to predict HCC development and prediction performances were evaluated using receiver operating characteristic curves.

Results

Entropy of HBV preS1, preS2 regions and several nucleotide points showed significant divergence between CHB and HCC patients. Using SLR, the classification of HCC/CHB groups achieved a mean area under the receiver operating characteristic curve (AUC) of 0.883 in the training data and 0.795 in the test data. The prediction model was also validated by a completely independent dataset from Hong Kong. The 10 selected nucleotide positions showed significantly different entropy between CHB and HCC patients. The HBV quasispecies also classified three clinical parameters, including HBeAg, HBVDNA, and Alkaline phosphatase (ALP) with the AUC value greater than 0.6 in the test data.

Conclusions

Using NGS and SLR, the association between HBV preS region nucleotide entropy and HCC development was validated in our study and this could promote the understanding of HCC progression mechanism.
Migrant experiences of sexual and gender based violence: a critical interpretative synthesis
Authors: Tan Sze Eng , Kuschminder Katie
Published: June 2022

Background

Gender based violence (GBV) is a critical issue and migrants are at higher risk of experiencing and being victimized by GBV. This critical interpretative synthesis (CIS) examines migrants experiences of GBV with a focus on different migrant groups and experiences at different stages of the migrant journey.

Method

The guiding question of this review is: “how do migrants experience gender-based violence?” A total of 84 studies were included in the CIS, of which 67 peer-reviewed academic articles were selected from 2356 studies found on WebofScience, MedLINE, and ProQuest, and 17 relevant studies from the grey literature were selected from the time period 2011 to 2020. All final studies were reviewed and synthesized using a critical inductive approach to formulate the key results.

Results

The results demonstrate a high prevalence of GBV amongst migrants, and in particular among vulnerable migrant groups such as forced migrants and irregular migrants, with an emerging focus on male victims. Findings of the CIS revealed three key themes: 1) Most GBV occurrences are rooted in unequal power dynamics; 2) Victims often live with long-lasting consequences that are worsened by their fear of disclosure and stigmatization; 3) There are differential understandings of victimhood across organizations, communities, and victims themselves. In order to support access, sampling, and methodological challenges in this field of research, this article also reports its findings on common risk-factors identified, consequences and coping mechanisms reported, protection policies targeting GBV, and finally, available databases and data collection methods.

Conclusion

Further directions for research should be encouraged to move beyond prevalence reporting into identifying risk-factors and possible prevention in both sexes. In addition, more research on GBV experiences throughout migrants’ journeys, and coping mechanisms should be encouraged.
Pelvic U-Net: multi-label semantic segmentation of pelvic organs at risk for radiation therapy anal cancer patients using a deeply supervised shuffle attention convolutional neural network
Authors: Lempart Michael , Nilsson Martin P. , Scherman Jonas , Gustafsson Christian Jamtheim , Nilsson Mikael , Alkner Sara , Engleson Jens , Adrian Gabriel , Munck af Rosenschöld Per , Olsson Lars E.
Published: June 2022

Background

Delineation of organs at risk (OAR) for anal cancer radiation therapy treatment planning is a manual and time-consuming process. Deep learning-based methods can accelerate and partially automate this task. The aim of this study was to develop and evaluate a deep learning model for automated and improved segmentations of OAR in the pelvic region.

Methods

A 3D, deeply supervised U-Net architecture with shuffle attention, referred to as Pelvic U-Net, was trained on 143 computed tomography (CT) volumes, to segment OAR in the pelvic region, such as total bone marrow, rectum, bladder, and bowel structures. Model predictions were evaluated on an independent test dataset (n = 15) using the Dice similarity coefficient (DSC), the 95th percentile of the Hausdorff distance (HD95), and the mean surface distance (MSD). In addition, three experienced radiation oncologists rated model predictions on a scale between 1–4 (excellent, good, acceptable, not acceptable). Model performance was also evaluated with respect to segmentation time, by comparing complete manual delineation time against model prediction time without and with manual correction of the predictions. Furthermore, dosimetric implications to treatment plans were evaluated using different dose-volume histogram (DVH) indices.

Results

Without any manual corrections, mean DSC values of 97%, 87% and 94% were found for total bone marrow, rectum, and bladder. Mean DSC values for bowel cavity, all bowel, small bowel, and large bowel were 95%, 91%, 87% and 81%, respectively. Total bone marrow, bladder, and bowel cavity segmentations derived from our model were rated excellent (89%, 93%, 42%), good (9%, 5%, 42%), or acceptable (2%, 2%, 16%) on average. For almost all the evaluated DVH indices, no significant difference between model predictions and manual delineations was found. Delineation time per patient could be reduced from 40 to 12 min, including manual corrections of model predictions, and to 4 min without corrections.

Conclusions

Our Pelvic U-Net led to credible and clinically applicable OAR segmentations and showed improved performance compared to previous studies. Even though manual adjustments were needed for some predicted structures, segmentation time could be reduced by 70% on average. This allows for an accelerated radiation therapy treatment planning workflow for anal cancer patients.
The potential role of herbal extract Wedelolactone for treating particle-induced osteolysis: an in vivo study
Authors: Lu Yung-Chang , Chang Ting-Kuo , Lin Tzu-Chiao , Yeh Shu-Ting , Fang Hsu-Wei , Huang Chun-Hsiung , Huang Chang-Hung
Published: June 2022

Background

Osteolysis is one of the most prevalent clinical complications affecting people who undergo total joint replacement (TJR). Wedelolactone (WDL) is a coumestan compound derived from the Wedelia chinensis plant and has been demonstrated to exhibit anti-inflammatory properties. This study aimed to investigate the oral administration of WDL as a potential treatment for particle-induced osteolysis using a well-established mice calvarial disease model.

Methods

Thirty-two C57BL/6 J mice were randomized into four groups: Sham, vehicle, osteolysis group with oral WDL treatment for 4 weeks (WDL 4w), and osteolysis group treated for 8 weeks (WDL 8w). Micro-CT was used to quantitatively analyze the bone mineral density (BMD), bone volume/tissue volume (BV/TV) and trabecular bone thickness (Tb.Th). Osteoclast numbers were also measured from histological slides by two investigators who were blind to the treatment used.

Results

The results from micro-CT observation showed that BMD in the WDL 8w group improved significantly over the vehicle group (p < 0.05), but there was no significant difference between WDL 4w and 8w for BV/TV and Tb.Th. Osteoclast numbers in the WDL 4w group were also lower than the vehicle group (p < 0.05), but the difference between WDL 8w and 4w groups was not significant.

Conclusions

Particle-induced osteolysis is an inevitable long-term complication after TJR. The results of this animal study indicate that an oral administration of WDL can help reduce the severity of osteolysis without adverse effects.
Patient-reported outcomes in a Chinese cohort of osteogenesis imperfecta unveil psycho-physical stratifications associated with clinical manifestations
Authors: Chen Peikai , Tan Zhijia , Qiu Anmei , Yin Shijie , Zhou Yapeng , Dong Zhongxin , Qiu Yan , Xu Jichun , Li Kangsen , Dong Lina , Shek Hiu Tung , Liu Jingwen , Yeung Eric H. K. , Gao Bo , Cheung Kenneth Man Chee , To Michael Kai-Tsun
Published: June 2022

Background

Osteogenesis imperfecta (OI) is a rare congenital disorder of the skeletal system, inflicting debilitating physical and psychological distress on patients and caregivers. Over the decades, much effort has been channeled towards understanding molecular mechanisms and developing new treatments. It has recently become more apparent that patient-reported outcome measurements (PROM) during treatment, healing and rehabilitation are helpful in facilitating smoother communication, refining intervention strategies and achieving higher quality of life. To date, systematic analyses of PROM in OI patients remain scarce.

Results

Here, utilizing a PROM Information System, we report a cross-sectional and longitudinal study in a southern Chinese cohort of 90 OI patients, covering both the child and adult age-groups. In the child group where both self and parental surveys were obtained, we identified two clusters of comparable sizes showing different outlooks in physical mobility and emotional experiences. One cluster (Cluster 1) is more negative about themselves than the other (Cluster 2). A concordance of 84.7% between self and parental assessments was recorded, suggesting the stability and validity of PROM-based stratification. Clinical subtyping, deformity, leg length discrepancy, and limited joint mobility were significantly associated with this stratification, with Cluster 1 showing higher percentages of severe phenotypes than Cluster 2. Since OI is a genetic disorder, we performed genetic testing on 72 of the 90 patients, but found no obvious association between genotypes and the PROM stratification. Analyses of longitudinal data suggested that patients tended to stay in the same psychological state, in both clusters. Adult patients also showed a continuous spectrum of self-evaluation that matches their clinical manifestations.

Conclusion

By systematically analyzing patient-reported outcomes, our study demonstrated the link between the sociopsychological wellbeing of OI patients, and their clinical manifestations, which may serve as the basis for evaluating clinical interventions and help achieve better patient-centric medical practices. The lack of genotype-PROM association may be due to the diverse mutational spectrum in OI, which warrants further investigation when a larger sample size is available.
Effectiveness of relaxation techniques ‘as an active ingredient of psychological interventions’ to reduce distress, anxiety and depression in adolescents: a systematic review and meta-analysis
Authors: Hamdani Syed Usman , Zill-e-Huma  , Zafar Syeda Wajeeha , Suleman Nadia , Um-ul-Baneen  , Waqas Ahmed , Rahman Atif
Published: June 2022

Background

Adolescent depression and anxiety are among the leading contributors to health burden worldwide. ‘Relaxation Techniques (RTs)’ are a “set of strategies to improve physiological response to stress” and are frequently cited as an active ingredient of trans-diagnostic, psychosocial interventions for scaling-up care for preventing and treating these conditions in adolescents. However, there is a little evidence on the effectiveness of ‘relaxation techniques’ for this age group.

Aim

As a part of the Wellcome Trust’s Active Ingredients commission, we did a systematic review and meta-analysis to evaluate the effectiveness of RTs to reduce the symptoms of distress, anxiety and depression in young people, aged 14 to 24 years old, globally.

Methods

We searched 10 academic databases to include 65 Randomized Controlled Trials (RCTs) of relaxation-based interventions for young people with the symptoms of anxiety and depression. Primary outcomes were reduction in symptoms of distress, anxiety and/or depression. We employed the Cochrane risk of bias tool and GRADE (Grading of Recommendations, Assessment, Development and Evaluations) guidelines to assess certainty of outcomes pertaining to anxiety, depression and distress. Standardized mean difference was estimated using effect size.

Results

The analysis of 65 RCTs with 8009 young people showed that RTs were highly effective in treating anxiety (pooled effect size of (Standardized Mean Difference-SMD) − 0.54 (95%CI− 0.69 to − 0.40); moderately effective in reducing distress (SMD = − 0.48, 95%CI− 0.71 to − 0.24) and had only a weak effect on improving depression in young people (SMD = − 0.28 (95%CI− 0.40% to − 0.15). Face-to-face delivered relaxation techniques yielded higher effect size (SMD = − 0.47, 95% CI − 0.64 to − 0.30) compared to online delivery (SMD = − 0.22, 95% CI − 0.48 to 0.04) for anxiety.

Conclusion

Most of the included studies were from High Income Countries (HICs) and had a high risk of bias. Further high-quality studies with low risk of bias, especially from low resource settings are needed to evaluate the evidence for effectiveness of RTs as an active ingredient of psychological interventions to reduce the symptoms of distress, anxiety and depression in young people.
Fusobacterium nucleatum promotes the development of acute liver failure by inhibiting the NAD+ salvage metabolic pathway
Authors: Cao Pan , Chen Qian , Shi Chunxia , Wang Luwen , Gong Zuojiong
Published: June 2022

Background

Acute liver failure (ALF) patients are often accompanied by severe energy metabolism abnormalities and intestinal microecological imbalance. The intestinal mucosal barrier is severely damaged. Intestinal endotoxin can induce intestinal endotoxemia through the "Gut-Liver axis". More and more evidence shows that members of the gut microbiota, especially Fusobacterium nucleatum (F. nucleatum), are related to inflammatory bowel disease, but whether F. nucleatum is involved in the development of ALF and whether it affects the liver energy metabolism is unclear.

Methods

This study first detected the abundance of F. nucleatum and its effect on ALF disease, and explored whether F. nucleatum aggravated liver inflammation in vitro and in vivo.

Results

Our data showed that liver tissues of ALF patients contained different abundances of F. nucleatum, which were related to the degree of liver inflammation. In addition, we found that F. nucleatum infection affected the energy metabolism of the liver during the development of ALF, inhibited the synthesis pathway of nicotinamide adenine dinucleotide (NAD+)'s salvage metabolism, and promoted inflammatory damage in the liver. In terms of mechanism, F. nucleatum inhibited NAD+ and the NAD+-dependent SIRT1/AMPK signaling pathway, and promoted liver damage of ALF.

Conclusions

Fusobacterium nucleatum coordinates a molecular network including NAD+ and SIRT1 to control the progress of ALF. Detection and targeting of F. nucleatum and its related pathways may provide valuable insights for the treatment of ALF.
Metabolic profiling in periparturient dairy cows and its relation with metabolic diseases
Authors: Kabir Mojahidul , Hasan Md. Mehedi , Tanni Nobonita Sarker , Parvin Mst. Sonia , Asaduzzaman Md. , Ehsan Md. Amimul , Islam Md. Taohidul
Published: June 2022

Objective

Periparturient period is associated with multiple changes including serum concentration of macro minerals and drop in feed intake. Therefore, it is essential to know the actual concentrations of major macro minerals, glucose and ketone bodies in blood during the periparturient period. The objectives of the study were to study the dynamics of calcium, magnesium, phosphorus, and glucose in serum and ketone bodies in the urine of periparturient cows and to estimate the incidence of subclinical metabolic diseases.

Results

Results showed that all the urine samples were negative for ketone bodies. Incidence of subclinical form of hypocalcaemia, hypomagnesaemia, hypophosphatemia, and hypoglycemia in periparturient cows was 31.03%, 48.28%, 17.24% and 55.17%, respectively. Older cows with high BCS and milk yield were mostly affected with a subclinical form of hypocalcaemia and hypoglycemia. No significant differences were observed in serum level of macro minerals and glucose at different time points of periparturient period of cows fed with a balanced ration, and between two groups of cows those were given IV injection of calcium and magnesium on the day of parturition and those were not given. Age, parity, and milk yield had no significant effect on the concentration of calcium, magnesium, phosphorus, and glucose.
Aberrant DNA hydroxymethylation reshapes transcription factor binding in myeloid neoplasms
Authors: Li Jia , Hong Tingting , Wei Yue , Guo Lei , Lee Minjung , Yang Hui , Class Caleb , Yang Yaling , Wang Xiaoqiong , He Hua , Siwko Stefan , You M. James , Zhou Yubin , Garcia-Manero Guillermo , Huang Yun
Published: June 2022

Epigenetic abnormalities in DNA hydroxymethylation (5hmC) have been detected in patients with myeloid neoplasms, suggesting that 5hmC might act as a valuable epigenetic mark to reflect the disease status of myeloid neoplasms. Here, we report systematic genome-wide mapping of the DNA hydroxymethylomes in over 70 patients with myeloid neoplasms. Our integrative analysis leads to the identification of distinct 5hmC signatures that can sensitively discriminate patients from healthy individuals. At the molecular level, we unveiled dynamic 5hmC changes within key transcription factor (e.g., the CEBP family) binding motifs that are essential for hematopoiesis and myeloid lineage specification. 5hmC redistribution was found to alter the genome-wide binding of CEBP-α, thereby reprogramming transcriptional outputs to affect leukemia cell survival and stemness. Taken together, we provide a comprehensive 5hmC atlas representative of myeloid neoplasms, which sets the stage for future exploration on the epigenetic etiology of hematological malignancies. Mechanistically, our study further furnishes important insights into how abnormal 5hmC distribution in patients directly interrupts the binding of transcription factors to reshape transcriptional landscapes and aggravate leukemogenesis.
Mesenchymal stromal cell treatment improves outcomes in children with pneumonia post-hematopoietic stem cell transplantation: a retrospective cohort study
Authors: Qu Yuhua , Yang Xu , Zhang Xiaohong , Liu Shanshan , Liu Xiaoping , Liu Xiaodan , Luo Ailing , Cai Mansi , Yan Yaping , Xu Ling , Jiang Hua
Published: June 2022

Background

Hematopoietic stem cell transplantation (HSCT) is a standard therapy strategy for most malignant disorders in children. However, transplant-related pneumonia remains a major therapy challenge and mesenchymal stromal cells (MSCs) are rarely reported in HSCT-related pneumonia. The aim of our study was to assess the efficacy of MSC for HSCT-related pneumonia in children.

Methods

We retrospectively retrieved HSCT-related (severe and non-severe) pneumonia cases (aged < 18 years), which underwent MSC treatment (MSC group) or non-MSC treatment (non-MSC group) in Guangzhou Women and Children’s Medical Center, from December 2017 to December 2019. We investigated outcomes of the two different treatments among severe cases and non-severe cases, respectively. The primary endpoints were differences in overall cure rate and time to cure between MSC and non-MSC groups. The secondary endpoints were 180-day overall survival and cumulative cure rate.

Results

Finally, 31 severe pneumonia cases (16 in MSC group, 15 in non-MSC group) and 76 non-severe cases (31 in MSC group, 45 in non-MSC group) were enrolled in this study. Among severe pneumonia cases, overall cure rate in MSC group was significant higher than that in non-MSC group (12[75.0%] vs. 5[33.3%]; OR = 6.00, 95% CI [1.26–28.5]; p = 0.020); the time (days) to cure in MSC group was dramatically reduced compared with that in non-MSC group (36 [19–52] vs. 62 [42–81]; OR = 0.32, 95% CI [0.12–0.88]; p = 0.009); the 180-day overall survival in MSC group was better than that in non-MSC group (74.5% [45.4–89.6] vs. 33.3% [12.2–56.4]; p = 0.013). Among non-severe pneumonia cases, the time (days) to cure in MSC group was notably decreased compared with that in non-MSC group (28 [24–31] vs. 33 [26–39]; OR = 0.31, 95% CI [0.18–0.56]; p = 0.003). Compared with non-MSC group, MSC-treated patients achieved significant improvements of cumulative cure rate not only in severe pneumonia cases (p = 0.027), but also in non-severe cases (p < 0.001).

Conclusions

This study revealed that MSC treatment could contribute to improving outcomes in children with pneumonia post-HSCT, especially in severe cases. These findings suggest MSC treatment as a promising therapy for HSCT-related pneumonia in children.
Glioma-associated mesenchymal stem cells-mediated PD-L1 expression is attenuated by Ad5-Ki67/IL-15 in GBM treatment
Authors: Zhang Qing , Zhang Junwen , Wang Peiwen , Zhu Guidong , Jin Guishan , Liu Fusheng
Published: June 2022

Background

Glioblastoma (GBM) is a highly immunosuppressive and vascular malignant brain tumor. Current therapeutic strategies targeting tumor cells have limited efficacy because of the immunosuppressive microenvironment and vascularization. Glioma-associated mesenchymal stem cells (GA-MSCs) have been identified as important stromal components of the tumor microenvironment, owing to their contribution to tumor angiogenesis and their potential to drive glioma stem cells. However, there are no reports on the effect of oncolytic Ad5-Ki67/IL-15 on programmed death ligand 1 (PD-L1) expression and angiogenesis induced by GA-MSCs.

Methods

Flow cytometry was respectively performed to detect the PD-L1 of glioma cells and programmed death protein 1 (PD-1), CD3, CD4 and CD8 in lymphocytes, as well as distribution of the cell cycle. CCK-8 assay investigated the proliferation of glioma cells and GA-MSCs in vitro. Tumor-bearing nude mice were established with U87-Luc cells and treated with the viruses, and further the IVIS spectrum was utilized to obtain luciferase images. Finally, the expression of PD-L1 in tumor tissues was also investigated using western blotting.

Results

We found that GA-MSCs had potential to induce PD-L1 upregulation and involved in vascular mimicry in vitro. Importantly, Ad5-Ki67/IL-15 reduced PD-L1 expression of glioma cells and neovascularization by targeting GA-MSCs. Furthermore, despite the presence of GA-MSCs, the virus has the ability to generate potent antitumor efficacy in vitro and vivo.

Conclusions

These findings suggest the use of oncolytic Ad5-Ki67/IL-15 targeting GA-MSCs to treat GBM, indicating potential clinical applications.