bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and evaluation of child abuse web-based application for parent education & strengthen
Authors: Para Sharif , Shahrokhi Hassan , Maserat Elham , Mohammadzadeh Zeinab
Published: March 2024

Background

Child abuse is one of the major health and social problems in the world and has severe short-term and long-term consequences on children’s psychological, social and physical functioning. One of the effective strategies to control and prevent child abuse is training parent through web-based applications. The aim of this study is to design and evaluation of child abuse web-based application for parent education and strengthen.

Methods

This study is an applied-developmental study that performed in Razi Educational and Therapeutic Center in Tabriz. The study consisted of three main phases. The requirements assessment and design phases were completed between November 2022 and February 2023. The research community was parents referring to Razi Center and convenience sampling was used to select the samples. In firststage, a questionnaire was designed by searching in library sources and consulting with specialists for needs assessment and application design. The questionnaire was completed by psychiatric specialists, health information management and health information technology.Finally, the usability of designed application was evaluated with the participation of 30 parents and specialists.

Results

Based on the identified information elements and capabilities, a child abuse web-based application was designed. Application capabilities were such as concepts of child abuse, prevention and treatment strategies, parenting skills, childrens behavioral disorders, child abuse laws and interaction with clinical specialists. Finally, the result of the web-based application usability evaluation was evaluated at a good level equal to an average of 7.6 out of a total of 9 points.

Conclusions

The possibility of expressing experiences, exchanging message, attractiveness, ease of use, and accessibility of parents, they were designed as application features. The usability of the web-based application was satisfactory to users in various of overall functionality, display, terminology, learning ability and overall application capability.
Proportions and risk factors of chronic obstructive pulmonary disease and preserved ratio impaired spirometry, and association with small airway disease, in the positive screening older population from China: a cross-sectional study
Authors: Sang Le , Gong Xia , Huang Yunlei , Sun Jian
Published: March 2024

Background

Early diagnosing Chronic Obstructive Pulmonary Disease (COPD) is relatively difficult. Therefore, the concepts of preserved ratio impaired spirometry (PRISm) and small airway disease (SAD) were proposed to achieve early diagnosis for COPD. Besides, the occurrence of COPD is positively related to age. However, the relationship among COPD, PRISm, and SAD still requires clarification. Thus, we estimated the proportions and risk factors of COPD and PRISm in the positive screening participants, and searched the methods of early diagnosing COPD via the SAD indicators.

Methods

A total of 53,641 residents aged more than 60 years old from Shaoxing City, Zhejiang Province, China, completed a series of screening projects. And 2327 of positive screening participants ultimately finished bronchodilator tests. The data were statistically analyzed to figure out the proportions and risk factors of COPD and PRISm, and the efficacy of early diagnosing COPD by the SAD indicators.

Results

Totally 2229 positive screening participants were included, the proportion of PRISm was 6.3% (141/2229), and of COPD was 78.2% (1743/2229). Statistical analyses showed that COPD patients were more likely to be smokers, males, and older. And COPD patients had higher questionnaire scores, meaning that they were more prone to have family history of respiratory diseases and more severe respiratory symptoms. Additionally, COPD patients had lower maximal mid-expiratory flow (MMEF) pred, forced expiratory flow (FEF) 75pred, and FEF50pred. And we found that male sex and presence of respiratory symptoms might lead to COPD and PRISm. Also, the methods of early diagnosing COPD through the SAD indicators might be acceptable.

Conclusion

There is a close association between COPD and decreased small airway function (SAF) among the participants included. Age, smoking, male sex, worse SAF, and respiratory symptoms might cause the progressing from normal people to PRISm, then to COPD patients. Besides, the SAD indicators such as MMEFpred, FEF75pred, and FEF50pred were included in lung function tests and bronchodilator tests. Intriguingly, it was found that early diagnosing COPD via the SAD indicators might be feasible. In the future, early diagnosis for COPD requires further research.
A case with multiple nodules and mucosal oedema of the trachea and both bronchi induced by IgG4-related disease
Authors: Torii Atsushi , Oshima Kahori , Iwakoshi Akari , Oki Masahide
Published: March 2024

Background

IgG4-related disease is a systemic fibroinflammatory disease that is mainly seen in older men, and involves multiple organs, such as the pancreas and lungs. However, 75% of patients with IgG4-related lung disease are asymptomatic (if they are symptomatic, they mainly complain of nasal congestion, rhinorrhoea, chest pain, and cough) and are incidentally diagnosed through chest computed tomograph. Although, nodules in the airway and bronchial wall thickening are criteria for diagnosis, it is important that nodules have been reported in peripheral airways in several cases and rarely in the central airway.

Case presentation

A 74-year-old woman previously diagnosed with Mikulicz’s disease presented with swelling of the eyelid margin on both sides and visual disturbances. Computed tomography revealed extensive multiple nodules and mucosal oedema of the trachea and both bronchi. On flexible bronchoscopy under local anaesthesia, extensive lesions were observed from the middle of the trachea to the carina, extending into both segmental bronchi. The nodules were continuous with the normal respiratory tract mucosa, and the surfaces were smooth with minimal neovascularisation. Due to the solid nature of the lesion, obtaining an adequate amount of specimen was challenging. Therefore, we used a 1.9 mm cryoprobe under intubation, resulting in minimal bleeding. Subsequently, the patient was diagnosed with IgG4-related lung disease.

Conclusions

The present case is very rare because of the presence of multiple nodules, severe mucosal edema of the central airway and the absence of mediastinal lymphadenopathy, ground glass nodules, and lung masses. Therefore, it is important to consider differential diagnoses. Thus, we emphasise the importance of endobronchial cryobiopsy for obtaining an adequate number of tissue specimens in such cases to establish a definitive pathological diagnosis.
An imageology-based feasibility study of plating posterolateral tibial plateau fractures via an anterolateral trans-fibular-head approach
Authors: Zhou Xiaoji , Zhou Jiangshan , Qian Huajun , Qian Chunxiao , Xu Bin , Pan Lv , Chu Xudong
Published: March 2024

Background

There are many difficulties in the reduction and fixation of the tibial plateau fractures involving posterolateral quadrant using general plates via traditional approaches. By imaging the area above the fibulae capitulum, this study was performed to investigate the feasibility of the trans-fibular-head approach and to design an ideal anatomical plate.

Methods

MRI and CT scans of the knee joint were collected from 205 healthy volunteers (103 males, 102 females). Gender and height were used to divide the volunteers into groups separately: (1) A1 group and A2 group according to gender, (2) B1 group and B2 group according to height. Based on the images, several parameters were defined and measured to describe the space above the head of the fibula. In addition, differences in these parameters between genders and height were compared.

Results

The narrowest distance in the bony region was (10.96 ± 1.39) mm, (5.41 ± 0.97 mm) in the bone-ligament region. The narrowest distance of bony region in the A1 group was more than that in the A2 group (11.21 ± 1.62 mm, 10.85 ± 1.47 mm, p = 0.029). The narrowest distance of the bony region was (10.21 ± 1.42) mm and (11.65 ± 1.39) mm in the B1 group and B2 group, respectively (p = 0.002). The narrowest distance of the bone-ligament region was (5.39 ± 0.78) mm and (5.22 ± 1.21) mm in the A1 group and A2 group, respectively. No statistically significant differences were observed between the A1 group and the A2 group in terms of the narrowest distance of the bone-ligament region. In the B1 group, the narrowest distance of the bone-ligament region (5.18 ± 0.71 mm) was not significantly less than that (5.31 ± 0.91 mm) in the B2 group.

Conclusion

The space above the fibular capitellum was ample enough to place the plate for treating tibial plateau fractures involving posterolateral quadrant. The divisions of the lateral tibial plateau by 3-dimensional CT and the parameters of each region were crucial for providing guidance for designing the anatomical plate for the trans-fibular-head approach.
Forgotten ureteral stents: a systematic review of literature
Authors: Wang Xiaochuan , Ji Zhengguo , Yang Peiqian , Li Jun , Tian Ye
Published: March 2024

Background

The forgotten ureteral stents (FUS) is one of the late complications of stent placement. This systematic review summarized different aspects of FUS and focused on the problems and solutions related to FUS.

Methods

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. PubMed® and Embase® were searched from inception until October 1st, 2022. Eligible studies were those defining FUS as a stent unintentionally left in situ longer than at least 2 months.

Results

Total 147 studies with 1292 patients were finally included. The mean indwelling time of FUS was 33.5 months (range from 3 months to 32 years). The most common initial cause for stent placement was adjunct treatment to urolithiasis (79.2%). The major forgetting reasons were patient-related (83.9%), which included poor compliance, lapse in memory, and misconceptions about the necessity of timely removal. Primary presenting complaints were flank pain (37.3%), lower urinary tract symptoms (33.3%), and hematuria (22.8%). Encrustation (80.8%) and urinary tract infections (40.2%) were the most common complications detected in patients with FUS. Computed tomography evolving as a preferred imaging test (76.1%) was indispensable for evaluating encrustation, migration, fracture and other complicated situations in patients with FUS. Besides, evaluation of kidney function and infection status was also of great importance. Multiple and multimodal procedures (59.0%) were often necessitated to achieve the stent-free status, and were mostly endoscopic procedures. Cystoscope was most commonly used (64.8%). Retrograde ureteroscopy (43.4%) and antegrade stent removal (31.6%) were often used when dealing with more complicated situations. Extracorporeal shockwave lithotripsy (30.4%) was often used as adjunctive to other endoscopic procedures, but it sometimes failed. The decision regarding the choice of treatment is based on the volume and site of encrustation, the direction of migration, the site of fracture, kidney function and other urinary comorbidities.

Conclusions

FUS not only pose hazard to patients’ health, but also impose a huge economic burden on medical care. Thorough preoperative evaluation is fundamental to developing the treatment strategy. The management of FUS should be individualized using different treatment modalities with their advantages to minimize patients’ morbidities. Prevention is better than cure. Strengthening health education and setting a tracking program are of great importance to the prevention of FUS.
Correlation between the triglyceride-glucose index and arterial stiffness in Japanese individuals with normoglycaemia: a cross-sectional study
Authors: Cai Yuying , Sha Wenyue , Deng Hailian , Zhang Tuming , Yang Linlin , Wu Yueying , Luo Jinhua , Liu Guangyan , Yang Yu , Feng Dehui
Published: March 2024

Background

The association between the triglyceride-glucose (TyG) index and arterial stiffness in individuals with normoglycaemia remains unclear. We aimed to evaluate the relationship between the TyG index and arterial stiffness in Japanese individuals with normoglycaemia, providing additional evidence for predicting early arterial stiffness.

Methods

This study included 15,453 adults who participated in the NAGALA Physical Examination Project of the Murakami Memorial Hospital in Gifu, Japan, from 2004 to 2015. Data on clinical demographic characteristics and serum biomarker levels were collected. The TyG index was calculated from the logarithmic transformation of fasting triglycerides multiplied by fasting glucose, and arterial stiffness was measured using the estimated pulse wave velocity calculated based on age and mean blood pressure. The association between the TyG index and arterial stiffness was analysed using a logistic regression model.

Results

The prevalence of arterial stiffness was 3.2% (500/15,453). After adjusting for all covariates, the TyG index was positively associated with arterial stiffness as a continuous variable (adjusted odds ratio (OR) = 1.86; 95% Confidence Interval = 1.45–2.39; P<0.001). Using the quartile as the cutoff point, a regression analysis was performed for arterial stiffness when the TyG index was converted into a categorical variable. After adjusting for all covariates, the OR showed an upward trend; the trend test was P<0.001. Subgroup analysis revealed a positive association between the TyG index and arterial stiffness in Japanese individuals with normoglycaemia and different characteristics.

Conclusion

The TyG index in Japanese individuals with normoglycaemia is significantly correlated with arterial stiffness, and the TyG index may be a predictor of early arterial stiffness.
Evaluation of the prevalence of cardiometabolic disorders (diabetes, hypertension, and hyperlipidemia) diagnosed, undiagnosed, treated, and treatment goal in the elderly: Bushehr Elderly Health Program (BEH)
Authors: Ebrahimpur Mahbube , Mohammadi-Vajari Erfan , Sharifi Yasaman , Ghotbi Leila , Sarvari Masoumeh , Ayati Aryan , Hashemi Baran , Shadman Zhaleh , Khashayar Pouria , Ostovar Afshin , Fahimfar Noushin , Shafiee Gita , Shahmohamadi Elnaz , Yavari Tahereh , Nabipour Iraj , Larijani Bagher , Payab Moloud , Sharifi Farshad
Published: March 2024

As the population ages, the global burden of cardiometabolic disorders will increase. This study aimed to investigate the prevalence of cardiometabolic disorders (diabetes, hypertension, and hyperlipidemia) in elderly and to evaluate the effects of various variables including age, sex, education, marital status, smoking, income, physical activity, dementia and depressed mood on untreated cardiometabolic disorders. This was a cross sectional study conducted in Bushehr Elderly Health Program. A total 2381 participants were included. Medical data were collected by trained interviewers. The mean age of the study participants was 69.34 years. Proportions of diabetes, hypertension, hyperlipidemia and hypercholesterolemia were 43.25%, 75.71%, 64.74% and 35.31% respectively. Untreated diabetes prevalence was higher for males (OR = 1.60, 95%CI = 1.20–2.15), older adults (OR = 1.02, 95%CI = 1.00–1.05), and pre-frail status (OR = 0.69, 95%CI = 0.52–0.92). Males (OR = 2.16, 95%CI = 1.64–2.84) and current smokers (OR = 1.42, 95%CI = 1.05–1.93), in contrast to married participants (OR = 0.25, 95%CI = 0.08–0.78), people with higher education levels (OR = 0.51, 95%CI = 0.29–0.89) and dementia (OR = 0.78, 95%CI = 0.61–1.00) were more likely to have untreated HTN. Untreated dyslipidemia is more common in smokers (OR = 1.78, 95%CI = 1.19–2.66) and males (OR = 1.66, 95%CI = 1.21–2.27), while untreated hypercholesteremia is more common in males (OR = 3.20, 95%CI = 1.53–6.69) and is reported lower in people with dementia (OR = 0.53, 95%CI = 0.28–1.01).
Clinical analysis of the tooth-implant papilla for two narrow-diameter titanium-zirconium implants in the anterior area: prospective controlled clinical study
Authors: Herrera-Pérez Paola , García-De-La-Fuente Ana María , Andia-Larrea Eztizen , Marichalar-Mendia Xabier , Aguirre-Urizar José Manuel , Aguirre-Zorzano Luis Antonio
Published: March 2024

Background

Rehabilitation of the anterior area when the mesio-distal space is reduced is a challenge for the clinician, due to the patient’s anatomical limitations and aesthetic requirements. Narrow Diameter Implants (NDI) are an option of treatment when the standard diameter implant is not possible, but the evidence is scarce. This prospective clinical study aims to analyze the formation of the tooth-implant papilla between the implant and the adjacent natural tooth in the maxillary lateral incisors and mandibular incisors.

Methods

A total of 40 patients treated with NDI, of titanium-zirconium (Ti-Zr) alloy i.e., 2.9 mm Test Group (TG) and 3.3 mm Control Group (CG), were included. The mesiodistal distance between the adjacent natural teeth was used for implant selection, maintaining 1.5 mm between the fixation and the adjacent tooth. Clinical assessment was performed by a clinical examiner at 6 and 12 months after the final prosthesis. The primary variable was the Jemt Papillary Index. Also, implant survival rate (SR), complications, Implant Stability Quotient (ISQ), and patient-reported outcomes measures (PROMs) such as aesthetics, chewing, phonation, comfort, and self-esteem were analyzed.

Results

A significant amount of papilla filling was observed concerning the baseline, with a trend towards more formation of the papilla in the TG, with a JPI score of 3. No significant differences were observed between the two groups regarding implant SR, clinical parameters, and complications. In terms of PROMs, a higher satisfaction in the TG was observed, with significant intergroup differences for aesthetics, comfort, self-esteem, and primary stability ISQ (TG: 59.05 (SD: 5.4) vs. CG: 51.55 (SD: 5.7)).

Conclusions

The 2.9 mm diameter Ti-Zr implants achieved a formation of papilla similar to 3.3 mm implants in the anterior region at 12 months of follow-up after the final prosthetic restoration. The use of Ti-Zr implants with a diameter of 2.9 mm to rehabilitate single teeth in areas of the anterior region, where the mesiodistal distance is limited, showed favorable clinical results and a high degree of satisfaction during 1 year of observation similar to 3.3 mm dental implants.

Trial registration

This study was retrospectively registered in ClinicalTrials.gov with the number NCT05642520, dated 18/11/2022.
The role of a community health worker-delivered preconception and pregnancy intervention in achieving a more positive pregnancy experience: the Bukhali trial in Soweto, South Africa
Authors: Soepnel Larske M. , Mabetha Khuthala , Norris Shane A. , Motlhatlhedi Molebogeng , Nkosi Nokuthula , Klingberg Sonja , Lye Stephen , Draper Catherine E.
Published: March 2024

Background

A patient-centered, human-rights based approach to maternal care moves past merely reducing maternal mortality and morbidity, towards achieving a positive pregnancy experience. When evaluating an intervention, particularly in the context of the complex challenges facing maternal care in South Africa, it is therefore important to understand how intervention components are experienced by women. We aimed to qualitatively explore (i) factors influencing the pregnancy and postpartum experience amongst young women in Soweto, South Africa, and (ii) the influence of Bukhali, a preconception, pregnancy, and early childhood intervention delivered by community health workers (CHWs), on these experiences.

Methods

Semi-structured, in-depth interviews were conducted with 15 purposively sampled participants. Participants were 18–28-year-old women who (i) were enrolled in the intervention arm of the Bukhali randomized controlled trial; (ii) were pregnant and delivered a child while being enrolled in the trial; and (iii) had at least one previous pregnancy prior to participation in the trial. Thematic analysis, informed by the positive pregnancy experiences framework and drawing on a codebook analysis approach, was used.

Results

The themes influencing participants’ pregnancy experiences (aim 1) were participants’ feelings about being pregnant, the responsibilities of motherhood, physical and mental health challenges, unstable social support and traumatic experiences, and the pressures of socioeconomic circumstances. In terms of how support, information, and care practices influenced these factors (aim 2), four themes were generated: acceptance and mother/child bonding, growing and adapting in their role as mothers, receiving tools for their health, and having ways to cope in difficult circumstances. These processes were found to be complementary and closely linked to participant context and needs.

Conclusion

Our findings suggest that, among women aged 18–28, a CHW-delivered intervention combining support, information, and care practices has the potential to positively influence women’s pregnancy experience in South Africa. In particular, emotional support and relevant information were key to better meeting participant needs. These findings can help define critical elements of CHW roles in maternal care and highlight the importance of patient-centred solutions to challenges within antenatal care.

Trial registration

Pan African Clinical Trials Registry PACTR201903750173871, 27/03/2019.
Identification of health-related problems in youth: a mixed methods feasibility study evaluating the Youth Health Report System
Authors: Lostelius Petra V. , Gustavsson Catharina , Adolfsson Eva Thors , Söderlund Anne , Revenäs Åsa , Zakrisson Ann-Britt , Mattebo Magdalena
Published: March 2024

Background

Because poor health in youth risk affecting their entry in adulthood, improved methods for their early identification are needed. Health and welfare technology is widely accepted by youth populations, presenting a potential method for identifying their health problems. However, healthcare technology must be evidence-based. Specifically, feasibility studies contribute valuable information prior to more complex effects-based research. The current study assessed the process, resource, management, and scientific feasibility of the Youth Health Report System prototype, developed within a youth health clinic context in advance of an intervention study.

Methods

This mixed-methods feasibility study was conducted in a clinical setting. The process, resource, management, and scientific feasibility of the Youth Health Report System were investigated, as recommended in the literature. Participants were youth aged 16–23 years old, attending a youth health clinic, and healthcare professionals from three clinics. The youth participants used their smart phones to respond to Youth Health Report System health questions and healthcare professionals used their computer to access the results and for registration system entries. Qualitative data were collected from interviews with healthcare professionals, which were described with thematic analysis. Youth participants’ quantitative Youth Health Report System data were analyzed for descriptive statistics.

Results

Feasibility analysis of qualitative data from interviews with 11 healthcare professionals resulted in three themes: We expected it could be hard; Information and routines helped but time was an issue; and The electronic case report form was valuable in the health assessment. Qualitative data were collected from the Youth Health Report System. A total of 54 youth participants completed the evaluation questionnaire, and healthcare professionals retrieved information from, and made post-appointment system entries. Quantitative results revealed few missing items and acceptable data variability. An assessment template of merged qualitative and quantitative data guided a consensus discussion among the researchers, resulting in acceptable feasibility.

Conclusions

The process-, resource-, management-, and scientific feasibility aspects were acceptable, with some modifications, strengthening the potential for a successful Youth Health Report System intervention study.
TBK1, a prioritized drug repurposing target for amyotrophic lateral sclerosis: evidence from druggable genome Mendelian randomization and pharmacological verification in vitro
Authors: Duan Qing-Qing , Wang Han , Su Wei-Ming , Gu Xiao-Jing , Shen Xiao-Fei , Jiang Zheng , Ren Yan-Ling , Cao Bei , Li Guo-Bo , Wang Yi , Chen Yong-Ping
Published: March 2024

Background

There is a lack of effective therapeutic strategies for amyotrophic lateral sclerosis (ALS); therefore, drug repurposing might provide a rapid approach to meet the urgent need for treatment.

Methods

To identify therapeutic targets associated with ALS, we conducted Mendelian randomization (MR) analysis and colocalization analysis using cis-eQTL of druggable gene and ALS GWAS data collections to determine annotated druggable gene targets that exhibited significant associations with ALS. By subsequent repurposing drug discovery coupled with inclusion criteria selection, we identified several drug candidates corresponding to their druggable gene targets that have been genetically validated. The pharmacological assays were then conducted to further assess the efficacy of genetics-supported repurposed drugs for potential ALS therapy in various cellular models.

Results

Through MR analysis, we identified potential ALS druggable genes in the blood, including TBK1 [OR 1.30, 95%CI (1.19, 1.42)], TNFSF12 [OR 1.36, 95%CI (1.19, 1.56)], GPX3 [OR 1.28, 95%CI (1.15, 1.43)], TNFSF13 [OR 0.45, 95%CI (0.32, 0.64)], and CD68 [OR 0.38, 95%CI (0.24, 0.58)]. Additionally, we identified potential ALS druggable genes in the brain, including RESP18 [OR 1.11, 95%CI (1.07, 1.16)], GPX3 [OR 0.57, 95%CI (0.48, 0.68)], GDF9 [OR 0.77, 95%CI (0.67, 0.88)], and PTPRN [OR 0.17, 95%CI (0.08, 0.34)]. Among them, TBK1, TNFSF12, RESP18, and GPX3 were confirmed in further colocalization analysis. We identified five drugs with repurposing opportunities targeting TBK1, TNFSF12, and GPX3, namely fostamatinib (R788), amlexanox (AMX), BIIB-023, RG-7212, and glutathione as potential repurposing drugs. R788 and AMX were prioritized due to their genetic supports, safety profiles, and cost-effectiveness evaluation. Further pharmacological analysis revealed that R788 and AMX mitigated neuroinflammation in ALS cell models characterized by overly active cGAS/STING signaling that was induced by MSA-2 or ALS-related toxic proteins (TDP-43 and SOD1), through the inhibition of TBK1 phosphorylation.

Conclusions

Our MR analyses provided genetic evidence supporting TBK1, TNFSF12, RESP18, and GPX3 as druggable genes for ALS treatment. Among the drug candidates targeting the above genes with repurposing opportunities, FDA-approved drug-R788 and AMX served as effective TBK1 inhibitors. The subsequent pharmacological studies validated the potential of R788 and AMX for treating specific ALS subtypes through the inhibition of TBK1 phosphorylation.
Comparing anti-tumor and anti-self immunity in a patient with melanoma receiving immune checkpoint blockade
Authors: Chen Shuming , McMiller Tracee L. , Soni Abha , Succaria Farah , Sidhom John-William , Cappelli Laura C. , Casciola-Rosen Livia A. , Morales Isaac R. , Sankaran Preethi , Berger Alan E. , Deutsch Julie Stein , Zhu Qingfeng C. , Anders Robert A. , Hooper Jody E. , Pardoll Drew M. , Lipson Evan J. , Taube Janis M. , Topalian Suzanne L.
Published: March 2024

Background

Tumor regression following immune checkpoint blockade (ICB) is often associated with immune-related adverse events (irAEs), marked by inflammation in non-cancerous tissues. This study was undertaken to investigate the functional relationship between anti-tumor and anti-self immunity, to facilitate irAE management while promoting anti-tumor immunity.

Methods

Multiple biopsies from tumor and inflamed tissues were collected from a patient with melanoma experiencing both tumor regression and irAEs on ICB, who underwent rapid autopsy. Immune cells infiltrating melanoma lesions and inflamed normal tissues were subjected to gene expression profiling with multiplex qRT-PCR for 122 candidate genes. Subsequently, immunohistochemistry was conducted to assess the expression of 14 candidate markers of immune cell subsets and checkpoints. TCR-beta sequencing was used to explore T cell clonal repertoires across specimens.

Results

While genes involved in MHC I/II antigen presentation, IFN signaling, innate immunity and immunosuppression were abundantly expressed across specimens, irAE tissues over-expressed certain genes associated with immunosuppression (CSF1R, IL10RA, IL27/EBI3, FOXP3, KLRG1, SOCS1, TGFB1), including those in the COX-2/PGE2 pathway (IL1B, PTGER1/EP1 and PTGER4/EP4). Immunohistochemistry revealed similar proportions of immunosuppressive cell subsets and checkpoint molecules across samples. TCRseq did not indicate common TCR repertoires across tumor and inflammation sites, arguing against shared antigen recognition between anti-tumor and anti-self immunity in this patient.

Conclusions

This comprehensive study of a single patient with melanoma experiencing both tumor regression and irAEs on ICB explores the immune landscape across these tissues, revealing similarities between anti-tumor and anti-self immunity. Further, it highlights expression of the COX-2/PGE2 pathway, which is known to be immunosuppressive and potentially mediates ICB resistance. Ongoing clinical trials of COX-2/PGE2 pathway inhibitors targeting the major COX-2 inducer IL-1B, COX-2 itself, or the PGE2 receptors EP2 and EP4 present new opportunities to promote anti-tumor activity, but may also have the potential to enhance the severity of ICB-induced irAEs.
Rapid and cost-effective molecular karyotyping in wheat, barley, and their cross-progeny by chromosome-specific multiplex PCR
Authors: Ali Mohammad , Polgári Dávid , Sepsi Adél , Kontra Levente , Dalmadi Ágnes , Havelda Zoltán , Sági László , Kis András
Published: March 2024

Background

Interspecific hybridisation is a powerful tool for increasing genetic diversity in plant breeding programmes. Hexaploid wheat (Triticum aestivum, 2n = 42) × barley (Hordeum vulgare, 2n = 14) intergeneric hybrids can contribute to the transfer of agronomically useful traits by creating chromosome addition or translocation lines as well as full hybrids. Information on the karyotype of hybrid progenies possessing various combinations of wheat and barley chromosomes is thus essential for the subsequent breeding steps. Since the standard technique of chromosome in situ hybridisation is labour-intensive and requires specific skills. a routine, cost-efficient, and technically less demanding approach is beneficial both for research and breeding.

Results

We developed a Multiplex Polymerase Chain Reaction (MPCR) method to identify individual wheat and barley chromosomes. Chromosome-specific primer pairs were designed based on the whole genome sequences of ‘Chinese Spring’ wheat and ‘Golden Promise’ barley as reference cultivars. A pool of potential primers was generated by applying a 20-nucleotide sliding window with consecutive one-nucleotide shifts on the reference genomes. After filtering for optimal primer properties and defined amplicon sizes to produce an ordered ladder-like pattern, the primer pool was manually curated and sorted into four MPCR primer sets for the wheat A, B, and D sub-genomes, and for the barley genome. The designed MPCR primer sets showed high chromosome specificity in silico for the genome sequences of all 18 wheat and barley cultivars tested. The MPCR primers proved experimentally also chromosome-specific for the reference cultivars as well as for 13 additional wheat and four barley genotypes. Analyses of 16 wheat × barley F1 hybrid plants demonstrated that the MPCR primer sets enable the fast and one-step detection of all wheat and barley chromosomes. Finally, the established genotyping system was fully corroborated with the standard genomic in situ hybridisation (GISH) technique.

Conclusions

Wheat and barley chromosome-specific MPCR offers a fast, labour-friendly, and versatile alternative to molecular cytogenetic detection of individual chromosomes. This method is also suitable for the high-throughput analysis of distinct (sub)genomes, and, in contrast to GISH, can be performed with any tissue type. The designed primer sets proved to be highly chromosome-specific over a wide range of wheat and barley genotypes as well as in wheat × barley hybrids. The described primer design strategy can be extended to many species with precise genome sequence information.
Operative treatment of pulmonary primitive neuroectodermal tumor: a case report and literature review
Authors: Zhang Yiyuan , Shang Ke , Li Jialin , Sun Mengyao , Gu Xiaoying
Published: March 2024

Background

Pulmonary primitive neuroectodermal tumor (PNET), a member of the Ewing sarcoma family of tumors, is a rare malignancy that is associated with a grim prognosis. To date, fewer than 30 cases of pulmonary PNET have been reported. In this case report, we present the clinical details of a 12-year-old girl with pulmonary PNET who underwent surgical treatment. We also conducted an analysis and summary of other relevant studies and the surgical outcomes.

Case presentation

In May 2018, a 12-year-old girl was admitted with symptoms of cough and blood-tinged phlegm. A computed tomography scan revealed a large mass, measuring 12.9 cm × 8.1 cm, in the right middle and lower lungs. A percutaneous lung biopsy confirmed poorly differentiated tumor cells with a nested growth pattern. Immunohistochemical staining demonstrated positive expression of CD99, CD56, Vimentin, and Synaptophysin. The patient was diagnosed with pulmonary PNET. Following three cycles of neoadjuvant chemotherapy, a substantial reduction in tumor volume was observed. Subsequently, the patient underwent a surgical procedure involving pneumonectomy and partial resection of the left atrium with the assistance of cardiopulmonary bypass. The patient was discharged 37 days after surgery. During a three-year follow-up period, she exhibited no signs of tumor recurrence and has successfully returned to school.

Conclusions

This case highlights the successful management of an advanced PNET with neoadjuvant chemotherapy, pneumonectomy, and partial resection of the left atrium employing cardiopulmonary bypass. The patient remained disease-free after three years. Our analysis of surgically treated cases indicates that neoadjuvant chemotherapy can contribute to improved prognoses for PNET patients. It is crucial to emphasize that complete surgical excision remains the cornerstone of treatment, underscoring the importance of surgeons considering radical surgical approaches whenever feasible for patients with pulmonary PNETs.
Neonatal persistent pulmonary hypertension related to a novel TBX4 mutation: case report and review of the literature
Authors: Maddaloni Chiara , Ronci Sara , De Rose Domenico Umberto , Bersani Iliana , Campi Francesca , Di Nardo Matteo , Stoppa Francesca , Adorisio Rachele , Amodeo Antonio , Toscano Alessandra , Digilio Maria Cristina , Novelli Antonio , Chello Giovanni , Braguglia Annabella , Dotta Andrea , Calzolari Flaminia
Published: March 2024

TBX4 gene, located on human chromosome 17q23.2, encodes for T-Box Transcription Factor 4, a transcription factor that belongs to the T-box gene family and it is involved in the regulation of some embryonic developmental processes, with a significant impact on respiratory and skeletal illnesses. Herein, we present the case of a female neonate with persistent pulmonary hypertension (PH) who underwent extracorporeal membrane oxygenation (ECMO) on the first day of life and then resulted to have a novel variant of the TBX4 gene identified by Next-Generation Sequencing. We review the available literature about the association between PH with neonatal onset or emerging during the first months of life and mutations of the TBX4 gene, and compare our case to previously reported cases. Of 24 cases described from 2010 to 2023 sixteen (66.7%) presented with PH soon after birth. Skeletal abnormalities have been described in 5 cases (20%). Eleven cases (46%) were due to de novo mutations. Three patients (12%) required ECMO. Identification of this variant in affected individuals has implications for perinatal and postnatal management and genetic counselling. We suggest including TBX4 in genetic studies of neonates with pulmonary hypertension, even in the absence of skeletal abnormalities.
Associations between type 1 diabetes and pulmonary tuberculosis: a bidirectional mendelian randomization study
Authors: Jiang Yijia , Zhang Wenhua , Wei Maoying , Yin Dan , Tang Yiting , Jia Weiyu , Wang Churan , Guo Jingyi , Li Aijing , Gong Yanbing
Published: March 2024

Background

Type 1 diabetes mellitus (T1DM) has been associated with higher pulmonary tuberculosis (PTB) risk in observational studies. However, the causal relationship between them remains unclear. This study aimed to assess the causal effect between T1DM and PTB using bidirectional Mendelian randomization (MR) analysis.

Methods

Single nucleotide polymorphisms (SNPs) of T1DM and PTB were extracted from the public genetic variation summary database. In addition, GWAS data were collected to explore the causal relationship between PTB and relevant clinical traits of T1DM, including glycemic traits, lipids, and obesity. The inverse variance weighting method (IVW), weighted median method, and MR‒Egger regression were used to evaluate the causal relationship. To ensure the stability of the results, sensitivity analyses assess the robustness of the results by estimating heterogeneity and pleiotropy.

Results

IVW showed that T1DM increased the risk of PTB (OR = 1.07, 95% CI: 1.03–1.12, P < 0.001), which was similar to the results of MR‒Egger and weighted median analyses. Moreover, we found that high-density lipoprotein cholesterol (HDL-C; OR = 1.28, 95% CI: 1.03–1.59, P = 0.026) was associated with PTB. There was no evidence of an effect of glycemic traits, remaining lipid markers, or obesity on the risk of PTB. In the reverse MR analysis, no causal relationships were detected for PTB on T1DM and its relevant clinical traits.

Conclusion

This study supported that T1DM and HDL-C were risk factors for PTB. This implies the effective role of treating T1DM and managing HDL-C in reducing the risk of PTB, which provides an essential basis for the prevention and comanagement of concurrent T1DM and PTB in clinical practice.
Evaluating precipitation prediction skill for the pre- and postrainy seasons in South China in ECMWF subseasonal forecasts
Authors: Liu Yanan , Wu Qiong , Zhang Yizhi , Jiang Lujun
Published: March 2024

The rainy season in South China is divided into two phases, the pre- and postrainy seasons, according to the seasonal progression of the East Asian summer monsoon. The precipitation prediction skills for the two rainy seasons are investigated using subseasonal-to-seasonal (S2S) hindcast data from the European Centre for Medium-Range Weather Forecasts (ECMWF) for 2001–2019. The precipitation prediction skills and biases differ between the two rainy seasons, although some similar characteristics exist regarding circulation patterns and their influence on precipitation. During the two rainy seasons, the prediction ability of circulation at 850 hPa in key areas is relatively high, and the influence of circulation on precipitation is well captured; additionally, the relationship between circulation in key areas at 500 hPa and precipitation is less accurately constrained. Moreover, the precipitation prediction skill in the prerainy season is higher than that in the postrainy season. The main bias is that the 200 hPa westerly winds provide favorable divergence conditions for prerainy season precipitation (preprecipitation), while the postrainy season precipitation (postprecipitation) displays almost no correlation with the circulation in the reanalysis product; however, the simulated circulation at 200 hPa is closely connected to the precipitation in both rainy seasons; therefore, the lower prediction skill in the postrainy season is likely associated with overestimation of the complex physical mechanism of the upper-level circulation in the model.
Cutaneous application of SecurePig® FLASH, a Pig appeasing pheromone analogue, facilitates adaptation and manages social behavior during feeding in semi-extensive conditions
Authors: Chasles Manon , Marcet-Rius Míriam , Chou Jen-Yun , Teruel Eva , Pageat Patrick , Cozzi Alessandro
Published: March 2024

Background

Farm animals face several challenges throughout their lives, which can affect both their welfare and their productivity. Promoting adaptation in animals is one way of limiting these consequences. In various animal species, the use of maternal appeasing pheromones is efficient to reduce aggressiveness, improve adaptation and thus ensuring better welfare and productivity. This study sought to investigate the efficiency of a treatment with a Pig Appeasing Pheromone (PAP) on the behavior of pigs reared under semi-extensive conditions and exposed to a potential conflict– collective feeding. Animals (n = 14 divided in 2 groups of 7) were subjected to 3 different phases, (A) baseline - no pigs received the PAP, (B) SP − 2 out of the 7 pigs per group received the PAP and (C) AP– all pigs received the PAP. Behaviors related to feeding, aggression and locomotion were compared between the 3 phases of the study.

Results

Compared to the baseline period, we observed that the number of head knocks was reduced when some pigs (p < 0.001) and all pigs (p < 0.005) received the PAP. Similarly, we observed that the number of fleeing attempts was reduced when some pigs (p < 0.001) and all pigs (p < 0.001) were treated when compared to baseline. This number was lower in the AP phase than in the SP phase (p < 0.001). When all pigs were treated (AP), we also observed that they spent less time investigating the floor than during the two other phases (p < 0.001), but they seemed more likely to leave the feeder due to the presence or behavior of another pig of the group (SP vs. AP, p < 0.05).

Conclusions

The PAP application improved adaptation in pigs by reducing aggressiveness and promoting conflict avoidance. Those results validate the efficiency of the pheromonal treatment under semi-extensive rearing conditions to help pigs to cope with a challenging situation. Using PAP in the pig industry seems interesting to limit unwanted consequences of farm practices on animal welfare and productivity, by promoting their adaptation.
Development of a multiplex reverse transcription-quantitative PCR (qPCR) method for detecting common causative agents of swine viral diarrhea in China
Authors: Song Wenbo , Feng Yixue , Zhang Jiali , Kong Danni , Fan Jie , Zhao Mengfei , Hua Lin , Xiang Jinmei , Tang Xibiao , Xiao Shaobo , Peng Zhong , Wu Bin
Published: March 2024

Background

Diarrheal diseases caused by viral agents have led to a great morbidity, mortality, and economic loss in global pig industry. Porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and group A porcine rotavirus (RVA) are main causative agents of swine viral diarrhea with similar clinical signs on Chinese farms and their co-infection is also common. However, it is still lack of a convenient method to detect these four agents.

Methods

A TaqMan multiplex qPCR method was developed to detect PEDV, TGEV, PDCoV, and RVA, simultaneously. This method was then applied to investigate 7,342 swine fecal samples or rectal swabs, as well as 1,246 swine intestinal samples collected from 2075 farms in China in 2022.

Results

Minimum detection limits of this method were 3 copies/µL for PEDV, 4 copies/µL for TGEV, 8 copies/µL for RVA, and 8 copies/µL for PDCoV, suggesting a good sensitivity. No signals were observed by using this method detecting other viral agents commonly prevalent in pigs, which is suggestive of a good specificity. Application of this method on investigating clinical samples demonstrated a relatively high positive rate for PEDV (22.21%, 1907/8588) and RVA (44.00%, 3779/8588). In addition, co-infection between PEDV and RVA was observed on 360 investigated farms, accounting for 17.35% (360/2075) of the farms where co-infection events were screened.

Conclusions

A TaqMan multiplex qPCR method targeting PEDV, TGEV, PDCoV, and RVA was developed in this study. This method demonstrated a good specificity and sensitivity on investigating these four common viruses responsible for viral diarrhea on Chinese pig farms, which represents a convenient method for the monitoring and differential diagnosis of swine viral diarrhea.
Do US states’ responses to COVID-19 restore investor sentiment? Evidence from S&P 500 financial institutions
Authors: Chebbi Kaouther , Ammari Aymen , Athari Seyed Alireza , Abbass Kashif
Published: March 2024

This paper specifically investigates the effects of US government emergency actions on the investor sentiment–financial institution stock returns relationship. Despite attempts by many studies, the literature still provides no answers concerning this nexus. Using a new firm-specific Twitter investor sentiment (TS) metric and performing a panel smooth transition regression for daily data on 66 S&P 500 financial institutions from January 1 to December 31, 2020, we find that TS acts asymmetrically, nonlinearly, and time varyingly according to the pandemic situation and US states’ responses to COVID-19. In other words, we uncover the nexus between TS and financial institution stock returns and determine that it changes with US states’ reactions to COVID-19. With a permissive government response (the first regime), TS does not impact financial institution stock returns; however, when moving to a strict government response (the overall government response index exceeds the 63.59 threshold), this positive effect becomes significant in the second regime. Moreover, the results show that the slope of the transition function is high, indicating an abrupt rather than a smooth transition between the first and second regimes. The results are robust and have important policy implications for policymakers, investment analysts, and portfolio managers.