bluuebunny/crossref_metadata_2025 huggingface dataset:
Kidney disease in adults with Prader-Willi syndrome: international cohort study and systematic literature review
Authors: van Abswoude Denise H. , Pellikaan Karlijn , Nguyen Naomi , Rosenberg Anna G. W. , Davidse Kirsten , Hoekstra Franciska M. E. , Rood Ilse M. , Poitou Christine , Grugni Graziano , Høybye Charlotte , Markovic Tania P. , Caixàs Assumpta , Crinò Antonino , van den Berg Sjoerd A. A. , van der Lely Aart J. , de Graaff Laura C. G.
Published: July 2023

Background

Prader-Willi syndrome (PWS) is a rare, complex, genetic disorder characterized by hyperphagia, hypotonia, delayed psychomotor development, low muscle mass and hypothalamic dysfunction. Adults with PWS often have obesity, hypertension and type 2 diabetes mellitus (DM2), known risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD). Early symptoms of CVD and CKD may be masked by intellectual disability and inability to express physical complaints. Furthermore, kidney diseases are often asymptomatic. Therefore, renal and cardiovascular disease might be missed in patients with PWS. Microalbuminuria is an early sign of microvascular damage in the kidneys and other vascular beds. Therefore, we screened our adult PWS cohort for the presence of elevated urinary albumin and (micro)albuminuria.

Methods

We retrospectively collected anthropometric measurements, blood pressure, medical history, medication use, urine dipstick and biochemical measurements form electronic patient files. In addition, we performed a systematic literature review on kidney disease in PWS.

Results

We included 162 adults with genetically confirmed PWS (56% male, median age 28 years), of whom 44 (27%) had DM2. None had known CVD. All subjects had normal estimated glomerular filtration rate (eGFR) according to non-PWS reference intervals. Elevated urinary albumin or (micro)albuminuria was present in 28 (18%); 19 out of 75 (25%) had an increased urinary albumin-to-creatinine ratio (UACR) and 10 out of 57 (18%) had an increased urinary protein-to-creatinine ratio. Elevated urinary albumin was present at a young age (median age 26 (IQR 24-32) years) and was associated with an significantly higher BMI and LDL-cholesterol levels and higher prevalence of DM2, hypertension and dyslipidemia than those with normal UACR (p=0.027, p=0.019, p<0.001, p<0.001, p=0.011 and respectively).

Conclusion

Upon screening, one in every five adults with PWS had increased urinary albumin or (micro)albuminuria, early signs of microvascular disease. All had normal eGFR, according to non-PWS reference intervals, and none had a formal diagnosis of CVD. As muscle mass is low in PWS, creatinine levels and eGFR may be spuriously normal. Urinalysis in this patient group can be used as a screening tool for microvascular (kidney) disease. We propose an algorithm for the detection and management of microvascular disease in adults with PWS.
Physical activity and reduced risk of fracture in thyroid cancer patients after thyroidectomy — a nationwide cohort study
Authors: Kim Jinyoung , Han Kyungdo , Jung Jin-Hyung , Ha Jeonghoon , Jeong Chaiho , Heu Jun-Young , Lee Se-Won , Lee Jeongmin , Lim Yejee , Kim Mee Kyoung , Kwon Hyuk-Sang , Song Ki-Ho , Baek Ki-Hyun
Published: July 2023

Objectives

Levothyroxine suppressive therapy following thyroidectomy for thyroid cancer patients is considered as a risk factor for osteoporosis and fragility fractures. We evaluated the association of regular exercise and exercise habit change with fracture risk in adults older than 40 years who underwent thyroidectomy for thyroid cancer.

Methods

We enrolled the patients who underwent thyroidectomy for thyroid cancer older than 40 years between 2010 and 2016 from the Korean National Health Insurance Service data, and they were followed through 2019. Based on the questionnaire of health examination within 2 years before and after surgery, whether regular exercise once a week was evaluated. The reference group for the statistical analysis was the continuing lack of physical activity group that did not exercise before or after surgery. For fractures newly diagnosed during the follow-up period, univariate and multivariate Cox regression analyses were performed for risk evaluation.

Results

We evaluated 74,774 subjects, of whom 2,924 (3.9%) experienced any fractures during a median follow-up of 4.5 years. Compared with the group consistently lack of physical activity, the group that exercised before and after surgery showed a significant decrease in the risk of any fracture, vertebral fracture, and hip fracture: adjusted hazard ratio 0.848 (95% Confidence Interval 0.771–0.932), 0.703 (0.591–0.836), and 0.405 (0.224–0.732), respectively. For vertebral fracture, a significant reduction in fracture risk was confirmed even in patients who started their regular exercise after surgery: adjusted hazard ratio 0.779 (0.648–0.936). The risk reduction for vertebral fractures upon the initiation of exercise was found to be significant in the high-risk groups of patients: women and total thyroidectomy patients.

Conclusion

We suggest that maintaining or starting regular exercise after surgery may help prevent fractures in thyroid cancer patients older than 40 years who have undergone thyroidectomy.
Management of type 2 diabetes in pregnancy: a narrative review
Authors: Raets Lore , Ingelbrecht Anne , Benhalima Katrien
Published: July 2023

The prevalence of type 2 diabetes (T2DM) at reproductive age is rising. Women with T2DM have a similarly high risk for pregnancy complications as pregnant women with type 1 diabetes. To reduce adverse pregnancy and neonatal outcomes, such as preeclampsia and preterm delivery, a multi-target approach is necessary. Tight glycemic control together with appropriate gestational weight gain, lifestyle measures, and if necessary, antihypertensive treatment and low-dose aspirin is advised. This narrative review discusses the latest evidence on preconception care, management of diabetes-related complications, lifestyle counselling, recommendations on gestational weight gain, pharmacologic treatment and early postpartum management of T2DM.
Missingness adapted group informed clustered (MAGIC)-LASSO: a novel paradigm for phenotype prediction to improve power for genetic loci discovery
Authors: Gentry Amanda Elswick , Kirkpatrick Robert M. , Peterson Roseann E. , Webb Bradley T.
Published: July 2023

Introduction: The availability of large-scale biobanks linking genetic data, rich phenotypes, and biological measures is a powerful opportunity for scientific discovery. However, real-world collections frequently have extensive missingness. While missing data prediction is possible, performance is significantly impaired by block-wise missingness inherent to many biobanks.

Methods: To address this, we developed Missingness Adapted Group-wise Informed Clustered (MAGIC)-LASSO which performs hierarchical clustering of variables based on missingness followed by sequential Group LASSO within clusters. Variables are pre-filtered for missingness and balance between training and target sets with final models built using stepwise inclusion of features ranked by completeness. This research has been conducted using the UK Biobank (n > 500 k) to predict unmeasured Alcohol Use Disorders Identification Test (AUDIT) scores.

Results: The phenotypic correlation between measured and predicted total score was 0.67 while genetic correlations between independent subjects was high >0.86.

Discussion: Phenotypic and genetic correlations in real data application, as well as simulations, demonstrate the method has significant accuracy and utility for increasing power for genetic loci discovery.
Women's preferences for a new contraceptive under development: an exploratory study
Authors: Madden Tessa , Cohen Sarah Y. , Paul Rachel , Hurley Emily G. , Thomas Michael A. , Pauletti Giovanni
Published: July 2023

Objective

Currently available contraceptive methods do not meet the needs of all users. We sought to explore preferences of potential end-users regarding an on-demand, non-hormonal female contraceptive currently under development, using a web-based survey.

Study design

We recruited respondents for an exploratory survey via web link on Amazon Mechanical Turk (MTurk). Individuals were eligible if they were 18–44 years of age, identified as cis-gender female, were English-speaking, not pregnant, and had used barrier contraception previously. Respondents provided demographic characteristics and a basic reproductive history. We then provided a brief description of the potential contraceptive. Respondents were asked about their interest in the proposed contraceptive and preferences for method attributes.

Results

A total of 500 respondents completed the survey. Three-quarters of respondents were <35 years of age and 48.2% were currently using a barrier contraceptive method. Three-fourths of respondents (73.8%) expressed interest in using the contraceptive under development. The majority wanted the method to be small (≤2 inches), rod-shaped, and low cost (<$5 per use). More than half (59.4%) said it was important to be able to use the method without partners’ knowledge. The most reported potential concerns were vaginal irritation (51.6%) and lack of effectiveness (46.4%). Sixty percent of respondents were confident they could use the method correctly.

Discussion

Available contraceptive methods lack attributes preferred by some users. Development of new contraceptives frequently does not involve end-user input early in the development process. Individuals in this sample displayed interest in the proposed contraceptive and expressed preferences that can inform the further development of this method.
Apple (Malus × domestica Borkh.) dormancy – a review of regulatory mechanisms and agroclimatic requirements
Authors: González Noguer Carlota , Delgado Alvaro , Else Mark , Hadley Paul
Published: July 2023

Dormancy enables apple trees (Malus × domestica Borkh) to survive unfavorable weather conditions. The accumulation of cold temperatures during winter is required to release dormancy, whilst heat accumulation in spring promotes bud break and blooming. Chilling and heat requirements are used to anticipate cultivars’ suitability to local agroclimatic conditions. This review summarizes recent advances on the physiological and genetic mechanisms regulating dormancy in apple trees; and presents a compilation of available chilling and heat requirements for apple cultivars. Information shows a wide range of chilling requirements in existing cultivars. However, results reported for the same cultivar are highly variable between locations and methods used to estimate chilling; raising concerns on the suitability of using chill requirements to inform planting decisions. In the context of climate change, it is essential to ensure current knowledge on the physiological and genetic mechanisms regulating bud break guides the development of improved models that can generate better estimates of chilling and heat requirements in apple.
Surface plasmon resonance and microscale thermophoresis approaches for determining the affinity of perforin for calcium ions
Authors: Naneh Omar , Kozorog Mirijam , Merzel Franci , Gilbert Robert , Anderluh Gregor
Published: July 2023

Perforin is a pore-forming protein that plays a crucial role in the immune system by clearing virus-infected or tumor cells. It is released from cytotoxic granules of immune cells and forms pores in targeted lipid membranes to deliver apoptosis-inducing granzymes. It is a very cytotoxic protein and is therefore adapted not to act in producing cells. Its activity is regulated by the requirement for calcium ions for optimal activity. However, the exact affinity of perforin for calcium ions has not yet been determined. We conducted a molecular dynamics simulation in the absence or presence of calcium ions that showed that binding of at least three calcium ions is required for stable perforin binding to the lipid membrane. Biophysical studies using surface plasmon resonance and microscale thermophoresis were then performed to estimate the binding affinities of native human and recombinant mouse perforin for calcium ions. Both approaches showed that mouse perforin has a several fold higher affinity for calcium ions than that of human perforin. This was attributed to a particular residue, tryptophan at position 488 in mouse perforin, which is replaced by arginine in human perforin. This represents an additional mechanism to control the activity of human perforin.
Rai14 is a novel interactor of Invariant chain that regulates macropinocytosis
Authors: Lobos Patorniti Natacha , Zulkefli Khalisah Liyana , McAdam Martin E. , Vargas Pablo , Bakke Oddmund , Progida Cinzia
Published: July 2023

Invariant chain (Ii, CD74) is a type II transmembrane glycoprotein that acts as a chaperone and facilitates the folding and transport of MHC II chains. By assisting the assembly and subcellular targeting of MHC II complexes, Ii has a wide impact on the functions of antigen-presenting cells such as antigen processing, endocytic maturation, signal transduction, cell migration, and macropinocytosis. Ii is a multifunctional molecule that can alter endocytic traffic and has several interacting molecules. To understand more about Ii’s function and to identify further Ii interactors, a yeast two-hybrid screening was performed. Retinoic Acid-Induced 14 (Rai14) was detected as a putative interaction partner, and the interaction was confirmed by co-immunoprecipitation. Rai14 is a poorly characterized protein, which is believed to have a role in actin cytoskeleton and membrane remodeling. In line with this, we found that Rai14 localizes to membrane ruffles, where it forms macropinosomes. Depletion of Rai14 in antigen-presenting cells delays MHC II internalization, affecting macropinocytic activity. Intriguingly, we demonstrated that, similar to Ii, Rai14 is a positive regulator of macropinocytosis and a negative regulator of cell migration, two antagonistic processes in antigen-presenting cells. This antagonism is known to depend on the interaction between myosin II and Ii. Here, we show that Rai14 also binds to myosin II, suggesting that Ii, myosin II, and Rai14 work together to coordinate macropinocytosis and cell motility.
B lymphocytes transdifferentiate into immunosuppressive erythroblast-like cells
Authors: Yang Zhe , Wang Zheng , Wu Lei , Wang Ying , Xu Zhihui , Liu Ying , Wang Fangfang , Yu Duonan
Published: July 2023

Recent studies have demonstrated that a particular group of nucleated cells that exhibit erythroid markers (TER119 in mice and CD235a in humans) possess the ability to suppress the immune system and promote tumor growth. These cells are known as CD45+ erythroid progenitor cells (EPCs). According to our study, it appears that a subset of these CD45+ EPCs originate from B lymphocytes. Under conditions of hypoxia, mouse B lymphoma cells are capable of converting to erythroblast-like cells, which display phenotypes of CD45+TER119+ cells, including immunosuppressive effects on CD8 T cells. Furthermore, non-neoplastic B cells have similar differentiation abilities and exert the same immunosuppressive effect under anemia or tumor conditions in mice. Similar B cells exist in neonatal mice, which provides an explanation for the potential origin of immunosuppressive erythroid cells in newborns. Additionally, CD19+CD235a+ double-positive cells can be identified in the peripheral blood of patients with chronic lymphocytic leukemia. These findings indicate that some CD45+ EPCs are transdifferentiated from a selective population of CD19+ B lymphocytes in response to environmental stresses, highlighting the plasticity of B lymphocytes. We anticipate a potential therapeutic implication, in that targeting a specific set of B cells instead of erythroid cells should be expected to restore adaptive immunity and delay cancer progression.
Clodronate is not protective in lethal viral encephalitis despite substantially reducing inflammatory monocyte infiltration in the CNS
Authors: Spiteri Alanna G. , van Vreden Caryn , Ashhurst Thomas M. , Niewold Paula , King Nicholas J. C.
Published: July 2023

Bone marrow (BM)-derived monocytes induce inflammation and tissue damage in a range of pathologies. In particular, in a mouse model of West Nile virus (WNV) encephalitis (WNE), nitric oxide-producing, Ly6Chi inflammatory monocytes from the BM are recruited to the central nervous system (CNS) and contribute to lethal immune pathology. Reducing the migration of these cells into the CNS using monoclonal antibody blockade, immune-modifying particles or CSF-1R inhibitors reduces neuroinflammation, improving survival and/or clinical outcomes. Macrophages can also be targeted more broadly by administration of clodronate-encapsulated liposomes, which induce apoptosis in phagocytes. In this study, clodronate reduced the inflammatory infiltrate by 70% in WNE, however, surprisingly, this had no effect on disease outcome. More detailed analysis demonstrated a compensatory increase in neutrophils and enhanced activation status of microglia in the brain. In addition, we observed increased numbers of Ly6Chi BM monocytes with an increased proliferative capacity and expression of SCA-1 and CD16/32, potentially indicating output of immature cells from the BM. Once in the brain, these cells were more phagocytic and had a reduced expression of antigen-presenting molecules. Lastly, we show that clodronate also reduces non-myeloid cells in the spleen and BM, as well as ablating red blood cells and their proliferation. These factors likely impeded the therapeutic potential of clodronate in WNE. Thus, while clodronate provides an excellent system to deplete macrophages in the body, it has larger and broader effects on the phagocytic and non-phagocytic system, which must be considered in the interpretation of data.
Tumor-resident memory T cells as a biomarker of the response to cancer immunotherapy
Authors: Damei Isabelle , Trickovic Tatiana , Mami-Chouaib Fathia , Corgnac Stéphanie
Published: July 2023

Tumor-infiltrating lymphocytes (TIL) often include a substantial subset of CD8+ tissue-resident memory T (TRM) cells enriched in tumor-specific T cells. These TRM cells play a major role in antitumor immune response. They are identified on the basis of their expression of the CD103 (αE(CD103)β7) and/or CD49a (α1(CD49a)β1) integrins, and the C-type lectin CD69, which are involved in tissue residency. TRM cells express several T-cell inhibitory receptors on their surface but they nevertheless react strongly to malignant cells, exerting a strong cytotoxic function, particularly in the context of blocking interactions of PD-1 with PD-L1 on target cells. These TRM cells form stable conjugates with autologous tumor cells and interact with dendritic cells and other T cells within the tumor microenvironment to orchestrate an optimal in situ T-cell response. There is growing evidence to indicate that TGF-β is essential for the formation and maintenance of TRM cells in the tumor, through the induction of CD103 expression on activated CD8+ T cells, and for the regulation of TRM effector functions through bidirectional integrin signaling. CD8+ TRM cells were initially described as a prognostic marker for survival in patients with various types of cancer, including ovarian, lung and breast cancers and melanoma. More recently, these tumor-resident CD8+ T cells have been shown to be a potent predictive biomarker of the response of cancer patients to immunotherapies, including therapeutic cancer vaccines and immune checkpoint blockade. In this review, we will highlight the major characteristics of tumor TRM cell populations and the possibilities for their exploitation in the design of more effective immunotherapy strategies for cancer.
Glutaminolysis and peripheral CD4+ T cell differentiation: from mechanism to intervention strategy
Authors: Liu Tong , Ren Shaohua , Sun Chenglu , Zhao Pengyu , Wang Hao
Published: July 2023

To maintain the body’s regular immune system, CD4+ T cell homeostasis is crucial, particularly T helper (Th1, Th17) cells and T regulatory (Treg) cells. Abnormally differentiated peripheral CD4+ T cells are responsible for the occurrence and development of numerous diseases, including autoimmune diseases, transplantation rejection, and irritability. Searching for an effective interventional approach to control this abnormal differentiation is therefore especially important. As immunometabolism progressed, the inherent metabolic factors underlying the immune cell differentiation have gradually come to light. Mounting number of studies have revealed that glutaminolysis plays an indelible role in the differentiation of CD4+ T cells. Besides, alterations in the glutaminolysis can also lead to changes in the fate of peripheral CD4+ T cells. All of this indicate that the glutaminolysis pathway has excellent potential for interventional regulation of CD4+ T cells differentiation. Here, we summarized the process by which glutaminolysis regulates the fate of CD4+ T cells during differentiation and further investigated how to reshape abnormal CD4+ T cell differentiation by targeting glutaminolysis.
Bulbar involvement and cognitive features in amyotrophic lateral sclerosis: a retrospective study on 347 patients
Authors: Aiello Edoardo Nicolò , Solca Federica , Torre Silvia , Patisso Valerio , De Lorenzo Alberto , Treddenti Mauro , Colombo Eleonora , Maranzano Alessio , Morelli Claudia , Doretti Alberto , Verde Federico , Silani Vincenzo , Ticozzi Nicola , Poletti Barbara
Published: July 2023

Background

This study aimed at clarifying the role of bulbar involvement (BI) as a risk factor for cognitive impairment (CI) in non-demented amyotrophic lateral sclerosis (ALS) patients.

Methods

Data on N = 347 patients were retrospectively collected. Cognition was assessed via the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). On the basis of clinical records and ALS Functional Rating Scale-Revised (ALSFRS-R) scores, BI was characterized as follows: (1) BI at onset—from medical history; (2) BI at testing (an ALSFRS-R-Bulbar score ≤11); (3) dysarthria (a score ≤3 on item 1 of the ALSFRS-R); (4) severity of BI (the total score on the ALSFRS-R-Bulbar); and (5) progression rate of BI (computed as 12-ALSFRS-R-Bulbar/disease duration in months). Logistic regressions were run to predict a below- vs. above-cutoff performance on each ECAS measure based on BI-related features while accounting for sex, disease duration, severity and progression rate of respiratory and spinal involvement and ECAS response modality.

Results

No predictors yielded significance either on the ECAS-Total and -ALS-non-specific or on ECAS-Language/-Fluency or -Visuospatial subscales. BI at testing predicted a higher probability of an abnormal performance on the ECAS-ALS-specific (p = 0.035) and ECAS-Executive Functioning (p = 0.018). Lower ALSFRS-R-Bulbar scores were associated with a defective performance on the ECAS-Memory (p = 0.025). No other BI-related features affected other ECAS performances.

Discussion

In ALS, the occurrence of BI itself, while neither its specific features nor its presence at onset, might selectively represent a risk factor for executive impairment, whilst its severity might be associated with memory deficits.
The effects of FTO gene rs9939609 polymorphism on the association between colorectal cancer and dietary intake
Authors: Gholamalizadeh Maryam , Jonoush Mona , Mobarakeh Khadijeh Abbasi , Amjadi Arezoo , Alami Farkhondeh , Valisoltani Neda , Askarpour Seyed Ali , Azizi-Tabesh Ghasem , Mohammadian Mohammad Keshavarz , Akbari Mohammad Esmail , Rajabibazl Masoumeh , Alemrajabi Mahdi , Poodineh Jafar , Sadeghi Hossein , Hosseinzadeh Payam , Dahka Samaneh Mirzaei , Badeli Mostafa , Jarrahi Seyed Alireza Mosavi , Doaei Saeid
Published: July 2023

Background

FTO gene is associated with obesity, dietary intake, and the risk of colorectal cancer (CRC). In this study, patients with colorectal cancer were assessed for the interactions between FTO gene polymorphisms and dietary intake.

Methods

This case–control study was carried out on 450 participants aged 35–70 years including 150 patients with colorectal cancer and 300 healthy controls. Blood samples were collected in order to extract DNA and genotyping of FTO gene for rs9939609 polymorphism. A validated 168-item food frequency questionnaire (FFQ) and the Nutritionist-IV software were used to assess dietary intake.

Results

In the participants with the TT genotype of FTO rs9939609 polymorphism, CRC risk was significantly associated with higher intake of dietary fat (OR:1.87 CI95%:1.76–1.99, p = 0.04), vitamin B3 (OR:1.20 CI95%:1.08–1.65, p = 0.04), and vitamin C (OR:1.06 CI95%:1.03–1.15, p = 0.04) and lower intake of β-carotene (OR:0.98 CI95%:0.97–0.99, p = 0.03), vitamin E (OR:0.77 CI95%:0.62–0.95, p = 0.02), vitamin B1 (OR:0.15 CI95%:0.04–0.50, p < 0.01), and biotin (OR:0.72 CI95%:0.0.57–0.92, p = 0.01). No significant association was found between CRC and dietary intake in carriers of AA/AT genotypes after adjustments for the confounders.

Conclusion

CRC risk may be decreased by β-carotene, vitamins E, B1, and biotin only in those without the risk allele of the FTO gene. The association of CRC and diet may be influenced by FTO genotype. Further studies are warranted.
Induction treatment in high-grade B-cell lymphoma with a concurrent MYC and BCL2 and/or BCL6 rearrangement: a systematic review and meta-analysis
Authors: Zeremski Vanja , Kropf Siegfried , Koehler Michael , Gebauer Niklas , McPhail Ellen D. , Habermann Thomas , Schieppati Francesca , Mougiakakos Dimitrios
Published: July 2023

Background and aim

High-grade B cell lymphomas with concomitant MYC and BCL2 and/or BCL6 rearrangements (HGBCL-DH/TH) have a poor prognosis when treated with the standard R-CHOP-like chemoimmunotherapy protocol. Whether this can be improved using intensified regimens is still under debate. However, due to the rarity of HGBCL-DH/TH there are no prospective, randomized controlled trials (RCT) available. Thus, with this systematic review and meta-analysis we attempted to compare survival in HGBCL-DH/TH patients receiving intensified vs. R-CHOP(-like) regimens.

Methods

The PubMed and Web of Science databases were searched for original studies reporting on first-line treatment in HGBCL-DH/TH patients from 08/2014 until 04/2022. Studies with only localized stage disease, ≤10 patients, single-arm, non-full peer-reviewed publications, and preclinical studies were excluded. The quality of literature and the risk of bias was assessed using the Methodological Index for Non-Randomized Studies (MINORS) and National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Random-effect models were used to compare R-CHOP-(like) and intensified regimens regarding 2-year overall survival (2y-OS) and 2-year progression-free survival (2y-PFS).

Results

Altogether, 11 retrospective studies, but no RCT, with 891 patients were included. Only four studies were of good quality based on aforementioned criteria. Intensified treatment could improve 2y-OS (hazard ratio [HR]=0.78 [95% confidence interval [CI] 0.63-0.96]; p=0.02) as well as 2y-PFS (HR=0.66 [95% CI 0.44-0.99]; p=0.045).

Conclusions

This meta-analysis indicates that intensified regimens could possibly improve 2y-OS and 2y-PFS in HGBCL-DH/TH patients. However, the significance of these results is mainly limited by data quality, data robustness, and its retrospective nature. There is still a need for innovative controlled clinical trials in this difficult to treat patient population.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier CRD42022313234.
Research progress of circulating non-coding RNA in diagnosis and treatment of hepatocellular carcinoma
Authors: You Junqi , Xia Haoming , Huang Ziyue , He Risheng , Zhao Xudong , Chen Jiali , Liu Sidi , Xu Yi , Cui Yunfu
Published: July 2023

Hepatocellular carcinoma (HCC) is a highly malignant tumor that carries a significant risk of morbidity and mortality. This type of cancer is prevalent in Asia due to the widespread presence of risk factors. Unfortunately, HCC often goes undetected until it has reached an advanced stage, making early detection and treatment critical for better outcomes. Alpha-fetoprotein (AFP) is commonly used in clinical practice for diagnosing HCC, but its sensitivity and specificity are limited. While surgery and liver transplantation are the main radical treatments, drug therapy and local interventions are better options for patients with advanced HCC. Accurately assessing treatment efficacy and adjusting plans in a timely manner can significantly improve the prognosis of HCC. Non-coding RNA gene transcription products cannot participate in protein production, but they can regulate gene expression and protein function through the regulation of transcription and translation processes. These non-coding RNAs have been found to be associated with tumor development in various types of tumors. Noncoding RNA released by tumor or blood cells can circulate in the blood and serve as a biomarker for diagnosis, prognosis, and efficacy assessment. This article explores the unique role of circulating noncoding RNA in HCC from various perspectives.
Advances of the small molecule drugs regulating fibroblast-like synovial proliferation for rheumatoid arthritis
Authors: Tong Yitong , Li Xinyu , Deng Qichuan , Shi Jianyou , Feng Yibin , Bai Lan
Published: July 2023

Rheumatoid arthritis (RA) is a type of chronic autoimmune and inflammatory disease. In the pathological process of RA, the alteration of fibroblast-like synoviocyte (FLS) and its related factors is the main influence in the clinic and fundamental research. In RA, FLS exhibits a uniquely aggressive phenotype, leading to synovial hyperplasia, destruction of the cartilage and bone, and a pro-inflammatory environment in the synovial tissue for perpetuation and progression. Evidently, it is a highly promising way to target the pathological function of FLS for new anti-RA drugs. Based on this, we summed up the pathological mechanism of RA-FLS and reviewed the recent progress of small molecule drugs, including the synthetic small molecule compounds and natural products targeting RA-FLS. In the end, there were some views for further action. Compared with MAPK and NF-κB signaling pathways, the JAK/STAT signaling pathway has great potential for research as targets. A small number of synthetic small molecule compounds have entered the clinic to treat RA and are often used in combination with other drugs. Meanwhile, most natural products are currently in the experimental stage, not the clinical trial stage, such as triptolide. There is an urgent need to unremittingly develop new agents for RA.
Marker-assisted selection for transfer of QTLs to a promising line for drought tolerance in wheat (Triticum aestivum L.)
Authors: Sunilkumar V. P. , Krishna Hari , Devate Narayana Bhat , Manjunath Karthik Kumar , Chauhan Divya , Singh Shweta , Sinha Nivedita , Singh Jang Bahadur , T. L. Prakasha , Pal Dharam , Sivasamy M. , Jain Neelu , Singh Gyanendra Pratap , Singh Pradeep Kumar
Published: July 2023

Wheat crop is subjected to various biotic and abiotic stresses, which affect crop productivity and yield. Among various abiotic stresses, drought stress is a major problem considering the current global climate change scenario. A high-yielding wheat variety, HD3086, has been released for commercial cultivation under timely sown irrigated conditions for the North Western Plain Zone (NWPZ) and North Eastern Plain Zone NEPZ of India. Presently, HD3086 is one of the highest breeder seed indented wheat varieties and has a stable yield over the years. However, under moisture deficit conditions, its potential yield cannot be achieved. The present study was undertaken to transfer drought-tolerant QTLs in the background of the variety HD3086 using marker-assisted backcross breeding. QTLs governing Biomass (BIO), Canopy Temperature (CT), Thousand Kernel Weight (TKW), Normalized Difference Vegetation Index (NDVI), and Yield (YLD) were transferred to improve performance under moisture deficit conditions. In BC1F1, BC2F1, and BC2F2 generations, the foreground selection was carried out to identify the plants with positive QTLs conferring drought tolerance and linked to traits NDVI, CT, TKW, and yield. The positive homozygous lines for targeted QTLs were advanced from BC2F2 to BC2F4via the pedigree-based phenotypic selection method. Background analysis was carried out in BC2F5 and obtained 78-91% recovery of the recurrent parent genome in the improved lines. Furthermore, the advanced lines were evaluated for 2 years under drought stress to assess improvement in MABB-derived lines. Increased GWPS, TKW, and NDVI and reduced CT was observed in improved lines. Seven improved lines were identified with significantly higher yields in comparison to HD3086 under stress conditions.
Snow-cover loss attenuates the effects of N addition on desert nutrient cycling and microbial community
Authors: Yang Yaru , Liu Weiguo , Adams Jonathan M. , Song Bin
Published: July 2023

Desert ecosystems are sensitive to nitrogen (N) deposition. Considering snow is an important source of soil water, which is vital for plant growth and the biogeochemical cycle in desert areas. The effects of N deposition on biological soil crusts (BSCs) could be impacted by the removal of snow-cover. Here, we established a split-plot experiment in the Gurbantunggut Desert to examine the effects of snow-cover treatments on soil nutrients, enzyme activities, and the bacterial community under various N addition. The removal of snow-cover reduced the soil nutrients with light and moderate N addition, it also reduced the activities of urease (URE) and alkaline phosphatase (PHOS). The structural equation model (SEM) result indicated that low soil moisture (SMO) under snow-uncover inhibited the bacterial community, particularly suppressed bacterial diversity. Additionally, N addition indirectly affected the bacterial community via modifications to soil nutrients, and soil organic matter (SOM) (P < 0.001) was the crucial factor. Snow-uncover weakened soil nutrient and enzyme responses to N addition, indicating that snow-cover removal reduced the sensitivity of the desert ecosystem to N deposition. The study highlights the critical role of snow-cover in the desert ecosystem, raising our awareness of the ecological risks of BSCs in future global change.
Occupational resource profiles for an addressee orientation in occupational health management: a segmentation analysis
Authors: Friedrich Julian , Münch Anne-Kristin , Thiel Ansgar , Voelter-Mahlknecht Susanne , Sudeck Gorden
Published: July 2023

Introduction

In order to make sustainable decisions in precision prevention and health promotion, it is important to adequately assess people's demands and resources at work. To reach them in an addressee-oriented way, a segmentation of employers and employees based on occupational resources is a promising option. We identified profiles based on personal and perceived organizational resources. Furthermore, we used job demands for profile descriptions to obtain a deeper understanding of the profiles, characterizing people with similar occupational resources.

Methods

Personal occupational resources (occupational health literacy and self-efficacy) and perceived organizational resources (job decision latitude and participation in health at work) were assessed among employers and employees (n = 828) in small- and medium-sized enterprises in Germany. Job demands, socioeconomic status, and hierarchy levels in the company were used for further profile descriptions.

Results

A six-profile solution fitted best to the data based on cluster and profile analyses. One profile was characterized by above-average occupational resources, and another profile was characterized by below-average resources. The other four profiles showed that the individual and perceived organizational resources contrasted. Either organizational resources such as job decision latitude existed and personal resources were not highly developed or people had high individual motivation but few possibilities to participate in health at work. People with medium or high job demands as well as people with low socioeconomic status were most frequently in below-average resource profiles. Employers with high hierarchy levels were overrepresented in the above-average profiles with high organizational resources.

Discussion

Following the segmentation of the addressees, organizations might be supported in identifying needs and areas for prevention and health promotion. Interventions can be optimally developed, tailored, and coordinated through a deeper understanding of job demands and resources. Especially employees with low socioeconomic status and high job demands might profit from an addressee-orientated approach based on resource profiles. For example, employees obtain an overview of their occupational resource profile to recognize the development potential for safe and healthy behavior at work. Follow-up research should be used to examine how this feedback to employers and employees is implemented and how it affects the sustainability of tailored interventions.
The “Trinity” smart hospital construction policy promotes the development of hospitals and health management in China
Authors: Zhang Guang-Wei , Gong Mengchun , Li Hui-Jun , Wang Shuang , Gong Da-Xin
Published: July 2023

Recently, in order to comprehensively promote the development of medical institutions and solve the nationwide problems in the healthcare fields, the government of China developed an innovative national policy of “Trinity” smart hospital construction, which includes “smart medicine,” “smart services,” and “smart management”. The prototype of the evaluation system has been established, and a large number of construction achievements have emerged in many hospitals. In this article, the summary of this field was performed to provide a reference for medical workers, managers of hospitals, and policymakers.
AuReTim: an inexpensive and extensible open-source auditory psychomotor vigilance test
Authors: Straßer Torsten , Rothert Inga , Heine Thomas , Peters Tobias
Published: July 2023

Within a large joint research project aiming for characterizing the nonvisual effects of light (NiviL), AuReTim, a low-cost and extensible open-source portable psychomotor vigilance test using auditory stimuli was developed, tailored for field testing. Currently, an unprepared simple reaction time and a go/no-go paradigm using acoustic stimuli are implemented. AuReTim is based on inexpensive hardware, e.g., its core is a Raspberry Pi leveraging a touch screen as input. Its software is developed in Java™ using open-source libraries, therefore providing connectivity with other research setups, e.g., EEG, and easy extensibility with other stimulus paradigms. A simulation study proved the precise timing of AuReTim with limits of agreement between −1.86 and 1.67 ms. AuReTim combines the mobility of tablet-based psychomotor vigilance tests with the usability of conventional computer-based tests, which is especially helpful in field studies. AuReTim was successfully applied to study the effects of different lighting on alertness and proved to be a valuable tool for studies using the central nervous activation level as an outcome measure.
Heart Transplantation in High-Risk Recipients Employing Donor Marginal Grafts Preserved With Ex-Vivo Perfusion
Authors: Sponga Sandro , Vendramin Igor , Salman Jawad , Ferrara Veronica , De Manna Nunzio Davide , Lechiancole Andrea , Warnecke Gregor , Dralov Andriy , Haverich Axel , Ius Fabio , Bortolotti Uberto , Livi Ugolino , Avsar Murat
Published: July 2023

Extending selection criteria to face donor organ shortage in heart transplantation (HTx) may increase the risk of mortality. Ex-vivo normothermic perfusion (EVP) limits ischemic time allowing assessment of graft function. We investigated the outcome of HTx in 80 high-risk recipients transplanted with marginal donor and EVP-preserved grafts, from 2016 to 2021. The recipients median age was 57 years (range, 13–75), with chronic renal failure in 61%, impaired liver function in 11% and previous cardiac surgery in 90%; 80% were mechanically supported. Median RADIAL score was 3. Mean graft ischemic time was 118 ± 25 min, “out-of-body” time 420 ± 66 min and median cardiopulmonary bypass (CPB) time 228 min (126–416). In-hospital mortality was 11% and ≥moderate primary graft dysfunction 16%. At univariable analysis, CPB time and high central venous pressure were risk factors for mortality. Actuarial survival at 1 and 3 years was 83% ± 4%, and 72% ± 7%, with a median follow-up of 16 months (range 2–43). Recipient and donor ages, pre-HTx extracorporeal life support and intra-aortic balloon pump were risk factors for late mortality. In conclusion, the use of EVP allows extension of the graft pool by recruitment of marginal donors to successfully perform HTx even in high-risk recipients.
Effect of Native Vegetative Barriers to Prevent Wind Erosion: A Sustainable Alternative for Quinoa (Chenopodium quinoa Willd.) Production
Authors: Barrientos-Pérez Ermindo , Carevic-Vergara Felipe S. , Rodriguez Juan Pablo , Arenas-Charlín Jorge , Delatorre-Herrera José
Published: July 2023

The abandonment of ancestral techniques and the incorporation of new technologies in the production systems for the cultivation of quinoa has resulted in overexploitation of soils, a loss of fertility, water imbalance, a loss of native vegetation cover in plain land areas, and other negative effects on the southern Altiplano agricultural sustainable system. One of the methods to reduce wind erosion and improve soil environmental conditions is establishing a native vegetative barrier. The effect of t’ola [Parastrephia lepidophylla (Wedd.) Cabrera] as a vegetative barrier to prevent wind erosion was evaluated using the rod method, gravimetric humidity fluctuations, and soil quality measurements in traditional quinoa Real production plots. We found significant differences (p < 0.05) for mean erosion, sedimentation, net erosion, and mobilized soil variables. The highest loss of soil was reported for December and November. Vegetative barriers comprising three meters of t’ola better protected bare soils up to 7 m from the barrier, while in bare soils, the loss values were over 5 t ha−1 month−1. Soil humidity fluctuations in plots with t’ola vegetative barriers were highly significant for the distance factors and depth levels. There was a higher accumulation of gravimetric humidity (%) in bare soils from 1.5 m to the barrier (6.95%), while the insides of the vegetative barriers retained an average soil humidity of 6.37%. After two agricultural seasons in the quinoa plots, 62 t ha−1 per year of soils were lost due to a lack of vegetative barriers. Due to the large, cultivated area with quinoa (104,000 ha in 2014) in the Intersalar zone, wind erosion causes 6.48 million tons of soil loss yearly. T’ola vegetative barriers in the southern Altiplano of Bolivia favour the retention of sediments against wind erosion and soil protection for quinoa cultivation. Furthermore, incorporating native lupine increased soil fertility by 80% and protected the soil surface cover.
Polyphasic Characterization of Indigenous Potassium-Solubilizing Bacteria and Its Efficacy Studies on Maize
Authors: Saheewala Heena , Sanadhya Suman , Upadhyay Sudhir Kumar , Mohanty Santosh Ranjan , Jain Devendra
Published: July 2023

Potassium (K) helps crop plants to resist biotic and abiotic challenges and plays a vital role in biochemical, metabolic, and physiological processes. Due to intense agricultural practices over the past few decades, the soil K reserve has been observed to be decreasing globally. It is possible to view potassium-solubilizing bacteria (KSB), which uses a number of biological mechanisms to convert potassium from inaccessible forms and make it accessible to crop plants, as a viable method for managing K in soils with low potassium levels. The present study encompasses 44 KSB strains isolated from rhizospheric soils collected from southern Rajasthan, India and characterized based on morphological, biochemical, and molecular profiles. All the isolates exhibited potassium solubilization and were identified using ERIC, BOX, REP PCR, and 16 S rDNA amplification which exhibited significant diversity amongst the strains. A flame-photometric analysis revealed that significant amounts of potassium were released by isolates from muscovite mica on the 21st day of incubation. These KSB strains produced hydrolytic enzymes and plant growth-promoting activities at different environmental stresses. In comparison to the absolute control (control without KSB), maize seedlings grown from bacterized seeds showed an increase in shoot length, root length, leaf number, total chlorophyll content, and the expression of stress-related enzymes. These native strains, which have a variety of advantageous traits, may be able to replace synthetic K fertilizers in order to increase food production while reducing pollution and restoring degraded land for agricultural use.
High Emergence of Multidrug-Resistant Sequence Type 131 Subclade C2 among Extended-Spectrum β-Lactamase (ESBL)-Producing Escherichia coli Isolated from the University Hospital Bratislava, Slovakia
Authors: Koreň Ján , Andrezál Michal , Ozaee Elham , Drahovská Hana , Wawruch Martin , Liptáková Adriána , Maliar Tibor
Published: July 2023

The expansion of sequence type 131 (ST131) extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) represents major worldwide challenges. E. coli strains originating from healthcare facilities (labeled No. 1 and No. 2) of the University Hospital Bratislava (UHB) were analyzed for ST131 emergence, including its (sub)lineages and clonal relatedness. Antimicrobial resistance was determined in most strains. Of a total of 354 E. coli strains, 263 (74.3%) belonged to ST131; of these, 177 (67.3%) were from No. 1. Generally, among 260 ST131 E. coli, clades A/B were confirmed in 20 (7.7%), while clade C was noted in 240 (92.3%) strains; within them, subclades were detected as follows: C0 (17; 7.1%), C1 (3; 1.2%), and C2 (220; 91.7%). Among fifteen randomly selected E. coli strains that were investigated for ST and clonal relatedness, seven STs were identified: eight (53.3%) ST131, two (13.3%) ST73, and one each (6.7%) of ST10, ST12, ST14, ST1193, and ST1196. From No. 1, two ST131 in the first internal clinic and one ST131 from No. 2 in the aftercare department were highly clonally related, suggesting possible epidemiological association. Antimicrobial resistance was as follows: ciprofloxacin 93.8%, ceftazidime 78.4%, meropenem 0%, fosfomycin 2.9% and nitrofurantoin 1.4%. Prevention of ESBL-producing E. coli dissemination, especially for ST131 clade C2, is inevitably necessary for reducing drug resistance and decreasing healthcare-associated infections.
Peripheral Pulmonary Lesions Classification Using Endobronchial Ultrasonography Images Based on Bagging Ensemble Learning and Down-Sampling Technique
Authors: Wang Huitao , Shikano Kohei , Nakajima Takahiro , Nomura Yukihiro , Nakaguchi Toshiya
Published: July 2023

Lung cancer is the second most common cancer in the world, with an average five-year survival rate of 15 percent. Approximately 238,340 people were diagnosed in the US in 2023 based on the estimation of the American Cancer Society, and 127,070 people died from it. Cancer has always been a big problem for scientists. There has never been a good solution. So, the early detection of cancer is particularly important. In recent years, endobronchial ultrasonography (EBUS) images have been used more and more in the diagnosis of lung cancer because of their advantages of good real-time performance, no radiation, and superior performance. This research aims to develop a computer-aided diagnosis (CAD) system to differentiate benign and malignant peripheral pulmonary lesions (PPLs). The efficacy of this framework was evaluated on a dataset comprising 69 cases of lung carcinoma, encompassing 59 malignant instances and 10 benign cases. The final experimental results of accuracy, F1-Score, AUC, PPV, NPV, sensitivity, and specificity were 0.7, 0.63, 0.75, 0.84, 0.68, 0.56, and 0.85, respectively. From the experiment results, the developed CAD system has the potential ability to diagnose PPLs by using the EBUS images based on Deep Learning.