bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rare cause of air-leak syndrome in a premature newborn: a case report
Authors: Uzunhan Ozan , Yıldırım Mihriban Begüm , Eser Can , Öztarhan Kazım , Çelik Alaettin 
Published: July 2023

Abstract
Background
Pulmonary complications, such as airway leak syndrome, are common in preterm neonates; however, bronchial rupture is a rarely seen phenomenon.

Case Presentation
In this case, we present a preterm newborn who developed pneumomediastinum and pneumothorax. The pneumothorax persisted, despite placement of a thorax tube, requiring a thoracotomy to detect and treat the bronchial rupture.

Conclusion
Physicians should have a high suspicion of bronchial rupture in patients with persistent air leak syndrome, even after thorax tube placement and continuous negative pressure implementation.
Liver transient elastography values in healthy South African children
Authors: Rose Penelope C. , Cotton Mark F. , Otwombe Kennedy , Innes Steve , Nel Etienne D. 
Published: July 2023

Abstract
Background
Transient elastography (TE) is a rapid noninvasive ultrasound-based technology that measures liver stiffness as a surrogate for liver fibrosis and controlled attenuation parameter (CAP) as a measure of liver steatosis. However, normal ranges in children are not well defined in all populations. The aim of this study was to determine transient elastography values in healthy South African children.

Methods
From April 2019 to December 2021, children were recruited from the HIV negative control group of a cohort study. Only children neither overweight nor obese, without evidence of liver disease, no medical condition or medication associated with hepatic steatosis or fibrosis and normal metabolic profile were included in this cross-sectional analysis. Clinical data, anthropometry and blood samples were collected on the same day as transient elastography with controlled attenuation parameter was performed.

Results
104 children (median age 12.8 years [IQR 11.4–14.8, range 7.9–17.7 years]; 59 [57%] boys) were included. Liver stiffness was positively correlated with age (Pearson’s r = 0.39, p < 0.001). Median liver stiffness in boys (5.2 kPa [5th to 95th percentiles 3.6 to 6.8 kPa]) was greater than in girls (4.6 kPa [5th to 95th percentiles 3.6 to 6.1 kPa; p = 0.004]), but there was no difference by ethnicity. Median CAP was 179dB/m (5th to 95th percentiles 158 to 233dB/m). There was a positive correlation between CAP and body mass index (BMI) z-score, but no difference by age, sex, ethnicity or pubertal status.

Conclusion
Liver stiffness values increase with age and are higher in healthy South African boys than girls, whereas CAP values vary with BMI, but not with age or sex.
Continuity and care coordination of primary health care: a scoping review
Authors: Khatri Resham , Endalamaw Aklilu , Erku Daniel , Wolka Eskinder , Nigatu Frehiwot , Zewdie Anteneh , Assefa Yibeltal 
Published: July 2023

AbstractBackgroundHealthcare coordination and continuity of care conceptualize all care providers and organizations involved in health care to ensure the right care at the right time. However, systematic evidence synthesis is lacking in the care coordination of health services. This scoping review synthesizes evidence on different levels of care coordination of primary health care (PHC) and primary care.MethodsWe conducted a scoping review of published evidence on healthcare coordination. PubMed, Scopus, Embase, CINAHL, Cochrane, PsycINFO, Web of Science and Google Scholar were searched until 30 November 2022 for studies that describe care coordination/continuity of care in PHC and primary care. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines to select studies. We analysed data using a thematic analysis approach and explained themes adopting a multilevel (individual, organizational, and system) analytical framework.ResultsA total of 56 studies were included in the review. Most studies were from upper-middle-income or high-income countries, primarily focusing on continuity/care coordination in primary care. Ten themes were identified in care coordination in PHC/primary care. Four themes under care coordination at the individual level were the continuity of services, linkage at different stages of health conditions (from health promotion to rehabilitation), health care from a life-course (conception to elderly), and care coordination of health services at places (family to hospitals). Five themes under organizational level care coordination included interprofessional, multidisciplinary services, community collaboration, integrated care, and information in care coordination. Finally, a theme under system-level care coordination was related to service management involving multisectoral coordination within and beyond health systems.ConclusionsContinuity and coordination of care involve healthcare provisions from family to health facility throughout the life-course to provide a range of services. Several issues could influence multilevel care coordination, including at the individual (services or users), organizational (providers), and system (departments and sectors) levels. Health systems should focus on care coordination, ensuring types of care per the healthcare needs at different stages of health conditions by a multidisciplinary team. Coordinating multiple technical and supporting stakeholders and sectors within and beyond health sector is also vital for the continuity of care especially in resource-limited health systems and settings.
Increased prime edit rates in KCNQ2 and SCN1A via single nicking all-in-one plasmids
Authors: Dirkx N. , Weuring Wout J. , De Vriendt E. , Smal N. , van de Vondervoort J. , van ’t Slot Ruben , Koetsier M. , Zonnekein N. , De Pooter Tim , Weckhuysen S. , Koeleman B. P. C. 
Published: July 2023

AbstractBackgroundPrime editing (PE) is the most recent gene editing technology able to introduce targeted alterations to the genome, including single base pair changes, small insertions, and deletions. Several improvements to the PE machinery have been made in the past few years, and these have been tested in a range of model systems including immortalized cell lines, stem cells, and animal models. While double nicking RNA (dncRNA) PE systems PE3 and PE5 currently show the highest editing rates, they come with reduced accuracy as undesired indels or SNVs arise at edited loci. Here, we aimed to improve single ncRNA (sncRNA) systems PE2 and PE4max by generating novel all-in-one (pAIO) plasmids driven by an EF-1α promoter, which is especially suitable for human-induced pluripotent stem cell (hiPSC) models.ResultspAIO-EF1α-PE2 and pAIO-EF1α-PE4max were used to edit the voltage gated potassium channel gene KCNQ2 and voltage gated sodium channel gene SCN1A. Two clinically relevant mutations were corrected using pAIO-EF1α-PE2 including the homozygous truncating SCN1A R612* variant in HEK293T cells and the heterozygous gain-of-function KCNQ2 R201C variant in patient-derived hiPSC. We show that sncRNA PE yielded detectable editing rates in hiPSC ranging between 6.4% and 9.8%, which was further increased to 41% after a GFP-based fluorescence-activated cell sorting (FACS) cell sorting step. Furthermore, we show that selecting the high GFP expressing population improved editing efficiencies up to 3.2-fold compared to the low GFP expressing population, demonstrating that not only delivery but also the number of copies of the PE enzyme and/or pegRNA per cell are important for efficient editing. Edit rates were not improved when an additional silent protospacer-adjacent motif (PAM)-removing alteration was introduced in hiPSC at the target locus. Finally, there were no genome-wide off-target effects using pAIO-EF1α-PE2 and no off-target editing activity near the edit locus highlighting the accuracy of snc prime editors.ConclusionTaken together, our study shows an improved efficacy of EF-1α driven sncRNA pAIO-PE plasmids in hiPSC reaching high editing rates, especially after FACS sorting. Optimizing these sncRNA PE systems is of high value when considering future therapeutic in vivo use, where accuracy will be extremely important.
PARP inhibitor exerts an anti-tumor effect via LMO2 and synergizes with cisplatin in natural killer/T cell lymphoma
Authors: Wu Jiazhuo , Shi Cunzhen , Li Hongwen , Song Wenting , Huang Shuo , Zhang Jianxiang , Li Wencai , Li Zhaoming , Zhang Mingzhi 
Published: July 2023

Abstract
Background
PARP inhibitor (PARPi), as a kind of DNA damage repair inhibitor, has been shown to be effective in various solid tumors and hematologic malignancies. Natural killer/T cell lymphoma (NKTCL) is a highly aggressive malignancy, the treatment of which has long been a major challenge in the clinic. Here, we investigated the efficacy and mechanism of PARPi, and the therapeutic value of PARPi combined with cisplatin in NKTCL.

Methods
The cell proliferation, cell apoptosis, and cell cycle of NKTCL cells were detected respectively by CCK-8 and flow cytometry. The changes of mRNA expression and protein level were measured respectively by mRNA-sequencing, quantitative real-time PCR, western blotting, and immunofluorescence. LMO2 expression was detected by immunohistochemistry and western blotting. Targeted knockdown of LMO2 was conducted by short hairpin RNA. The tumor xenograft models were established to evaluate the efficacy of drugs in vivo.

Results
PARPi inhibited cell proliferation, promoted cell apoptosis, and induced S-phase cell cycle arrest in NKTCL cells. PARPi led to the accumulation of DNA damage by blocking DNA repair and DNA replication. Additionally, LMO2 deficiency reduced the sensitivity of NKTCL cells to PARPi. Finally, the combination of PARPi and cisplatin exhibited significant synergistic effects both in vitro and in vivo.

Conclusions
In summary, we found that PARPi exerted an anti-tumor effect via LMO2 and synergized with cisplatin in NKTCL, which provides the theoretical basis for the clinical application of PARPi.
Identification of a psychiatric risk gene NISCH at 3p21.1 GWAS locus mediating dendritic spine morphogenesis and cognitive function
Authors: Yang Zhi-Hui , Cai Xin , Ding Zhong-Li , Li Wei , Zhang Chu-Yi , Huo Jin-Hua , Zhang Yue , Wang Lu , Zhang Lin-Ming , Li Shi-Wu , Li Ming , Zhang Chen , Chang Hong , Xiao Xiao 
Published: July 2023

AbstractBackgroundSchizophrenia and bipolar disorder (BD) are believed to share clinical symptoms, genetic risk, etiological factors, and pathogenic mechanisms. We previously reported that single nucleotide polymorphisms spanning chromosome 3p21.1 showed significant associations with both schizophrenia and BD, and a risk SNP rs2251219 was in linkage disequilibrium with a human specificAlupolymorphism rs71052682, which showed enhancer effects on transcriptional activities using luciferase reporter assays in U251 and U87MG cells.MethodsCRISPR/Cas9-directed genome editing, real-time quantitative PCR, and public Hi-C data were utilized to investigate the correlation between theAlupolymorphism rs71052682 andNISCH. Primary neuronal culture, immunofluorescence staining, co-immunoprecipitation, lentiviral vector production, intracranial stereotaxic injection, behavioral assessment, and drug treatment were used to examine the physiological impacts of Nischarin (encoded byNISCH).ResultsDeleting theAlusequence in U251 and U87MG cells reduced mRNA expression ofNISCH, the gene locates 180 kb from rs71052682, and Hi-C data in brain tissues confirmed the extensive chromatin contacts. These data suggested that the genetic risk of schizophrenia and BD predicted elevatedNISCHexpression, which was also consistent with the observed higherNISCHmRNA levels in the brain tissues from psychiatric patients compared with controls. We then found that overexpression ofNISCHresulted in a significantly decreased density of mushroom dendritic spines with a simultaneously increased density of thin dendritic spines in primary cultured neurons. Intriguingly, elevated expression of this gene in mice also led to impaired spatial working memory in the Y-maze. Given that Nischarin is the target of anti-hypertensive agents clonidine and tizanidine, which have shown therapeutic effects in patients with schizophrenia and patients with BD in preliminary clinical trials, we demonstrated that treatment with those antihypertensive drugs could reduceNISCHmRNA expression and rescue the impaired working memory in mice.ConclusionsWe identify a psychiatric risk geneNISCHat 3p21.1 GWAS locus influencing dendritic spine morphogenesis and cognitive function, and Nischarin may have potentials for future therapeutic development.
Identification and characterization of a strong constitutive promoter stnYp for activating biosynthetic genes and producing natural products in streptomyces
Authors: Guo Wenli , Xiao Zhihong , Huang Tingting , Zhang Kai , Pan Hai-Xue , Tang Gong-Li , Deng Zixin , Liang Rubing , Lin Shuangjun 
Published: July 2023

Abstract
Background
Streptomyces are well known for their potential to produce various pharmaceutically active compounds, the commercial development of which is often limited by the low productivity and purity of the desired compounds expressed by natural producers. Well-characterized promoters are crucial for driving the expression of target genes and improving the production of metabolites of interest.

Results
A strong constitutive promoter, stnYp, was identified in Streptomyces flocculus CGMCC4.1223 and was characterized by its effective activation of silent biosynthetic genes and high efficiency of heterologous gene expression. The promoter stnYp showed the highest activity in model strains of four Streptomyces species compared with the three frequently used constitutive promoters ermEp*, kasOp*, and SP44. The promoter stnYp could efficiently activate the indigoidine biosynthetic gene cluster in S. albus J1074, which is thought to be silent under routine laboratory conditions. Moreover, stnYp was found suitable for heterologous gene expression in different Streptomyces hosts. Compared with the promoters ermEp*, kasOp*, and SP44, stnYp conferred the highest production level of diverse metabolites in various heterologous hosts, including the agricultural-bactericide aureonuclemycin and the antitumor compound YM-216391, with an approximately 1.4 − 11.6-fold enhancement of the yields. Furthermore, the purity of tylosin A was greatly improved by overexpressing rate-limiting genes through stnYp in the industrial strain. Further, the yield of tylosin A was significantly elevated to 10.30 ± 0.12 g/L, approximately 1.7-fold higher than that of the original strain.

Conclusions
The promoter stnYp is a reliable, well-defined promoter with strong activity and broad suitability. The findings of this study can expand promoter diversity, facilitate genetic manipulation, and promote metabolic engineering in multiple Streptomyces species.
Preclinical trial of the effectiveness of a safety nasogastric tube to detect the tube position based on tidal volume and pepsin assay results in the gastrointestinal tract of Macaca fascicularis
Authors: Nuzul Sigit Mohammad , Kartinah Neng Tine , Nur Busjra M. , Ilyas Ermita I. Ibrahim 
Published: July 2023

Abstract
Background
Tube misplacement into the tracheobronchial tract is associated with pneumothorax in 0.5% of cases. NGT verification only detects the position of the tube at the end of the procedure. Therefore, a safe nasogastric tube (SNGT) was created to detect the NGT position in real time in a simple and inexpensive way. This study aimed to prove the effectiveness of the SNGT prototype in Macaca fascicularis.

Result
An SNGT producing 50% of the TV had 100% sensitivity and specificity in detecting the position of the tube at 100% of the TV, with a sensitivity of 100% and a specificity of 87.5%. There was a significant difference between the movement of the SNGT 50% TV and SNGT 100% TV airbags (p ≤ 0.05). However, there was no significant difference between the accuracy of placement of the 50% TV SNGT, 100% TV SNGT, and conventional NGT (p > 0.05). The pepsin enzyme had better sensitivity (100%) than pH paper (91.66%) in detecting the end-of-procedure tube position. This research has the potential to advance into human clinical trials.

Conclusion
SNGTs are highly effective in detecting the NGT position inside the respiratory and digestive tracts to prevent misplacement.
Health-related quality of life and its associated factors among outpatients with heart failure: a cross-sectional study
Authors: Jarab Anan S. , Hamam Hanan W. , Al-Qerem Walid A. , Heshmeh Shrouq R. Abu , Mukattash Tareq L. , Alefishat Eman A. 
Published: July 2023

Abstract
Background
Heart Failure (HF) is a chronic disease associated with life-limiting symptoms that could negatively impact patients’ health-related quality of life (HRQOL). This study aimed to evaluate HRQOL and explore the factors associated with poor HRQOL among patients with HF in Jordan.

Methods
This cross-sectional study used the validated Arabic version of the Minnesota Living with Heart Failure Questionnaire to assess HRQOL in outpatients with HF visiting cardiology clinics at two public hospitals in Jordan. Variables were collected from medical records and custom-designed questionnaires, including socio-demographics, biomedical variables, and disease and medication characteristics. Ordinal regression analysis was used to explore variables associated with poor HRQOL among HF patients.

Results
Ordinal regression analysis showed that the number of HF medications (P < 0.05) and not taking a loop diuretic (P < 0.05) significantly increased HRQOL, while the number of other chronic diseases (P < 0.05), stage III/IV of HF (P < 0.01), low monthly income (P < 0.05), and being unsatisfied with the prescribed medications (P < 0.05) significantly decreased HRQOL of HF patients.

Conclusions
Although the current study demonstrated low HRQOL among patients with HF in Jordan, HRQOL has a considerable opportunity for improvement in those patients. Variables identified in the present study, including low monthly income, higher New York Heart Association (NYHA) classes, a higher number of comorbidities, and/or taking a loop diuretic, should be considered in future intervention programs, aiming to improve HRQOL in patients with HF.
Effect of on-site first aid for industrial injuries on healthcare utilization after medical treatment: a 4-year retrospective longitudinal study
Authors: Kim Jinhyun , Kim Hyunkyu , Park Eun-Cheol , Jang Sung-In 
Published: July 2023

Abstract
Background
The number of industrially injured workers (IIW) is increasing in Korea. However, little research has been conducted on whether first aid is performed at industrial sites or on the association between first aid for industrial injuries and the prognosis of IIW, including healthcare utilization.

Methods
A total of 3,092 participants (2,562 males and 530 females) were analyzed during the 4-year study period, which contributed to 11,167 observations. Healthcare utilization was evaluated based on the number of outpatient visits, hospitalizations, and duration of hospitalization using a generalized estimating equation Poisson regression. Several time-varying socioeconomic characteristics and information about the injury were adjusted, and transfer time to the medical institutions was also considered.

Results
During 4-year after the termination of medical treatment, participants who had not receive first aid visited outpatient clinics 15.243 times per year, and those who had visited 13.928 times per year, which is 16.16% less (adjusted relative risk [aRR]: 0.838, 95% CI = 0.740–0.950). Participants who had received on-site first aid with less than a 0.5-hour transfer time to the medical institutions visited outpatient clinics 14.87% less per year than those who had not received first aid (aRR: 0.851, 95% CI = 0.750–0.966).

Conclusion
To reduce the long-term outpatient utilization rate for IIW after medical treatment, on-site first aid must be provided in a timely manner. Employee education and first aid training are also necessary.
ChatGPT and large language models in academia: opportunities and challenges
Authors: Meyer Jesse G. , Urbanowicz Ryan J. , Martin Patrick C. N. , O’Connor Karen , Li Ruowang , Peng Pei-Chen , Bright Tiffani J. , Tatonetti Nicholas , Won Kyoung Jae , Gonzalez-Hernandez Graciela , Moore Jason H. 
Published: July 2023

AbstractThe introduction of large language models (LLMs) that allow iterative “chat” in late 2022 is a paradigm shift that enables generation of text often indistinguishable from that written by humans. LLM-based chatbots have immense potential to improve academic work efficiency, but the ethical implications of their fair use and inherent bias must be considered. In this editorial, we discuss this technology from the academic’s perspective with regard to its limitations and utility for academic writing, education, and programming. We end with our stance with regard to using LLMs and chatbots in academia, which is summarized as (1) we must find ways to effectively use them, (2) their use does not constitute plagiarism (although they may produce plagiarized text), (3) we must quantify their bias, (4) users must be cautious of their poor accuracy, and (5) the future is bright for their application to research and as an academic tool.
Decrease of thyroid function after ischemic stroke is related to stroke severity
Authors: Sidorov Evgeny , Paul Aruna , Xu Chao , Nouh Claire Delpirou , Chen Allshine , Gosmanova Albina , Gosmanov Niyaz , Gordon David Lee , Baranskaya Irina , Chainakul Juliane , Hamilton Robert , Mdzinarishvili Alexander 
Published: July 2023

Abstract
Background
Thyroid hormones are of fundamental importance for brain function. While low triiodothyronine levels during acute ischemic stroke (AIS) are associated with worse clinical outcomes, dynamics of thyroid function after AIS remains unknown. Thus, we longitudinally evaluated thyroid hormones after stroke and related them to stroke severity.

Methods
We prospectively traced thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxin (fT4) levels from the hyper-acute (within 24 h) to acute (3–5 days) and chronic (3–6 months) stages of ischemic stroke using a mixed regression model. Then, we analyzed whether stroke severity at presentation, expressed by National Institute of Health Stroke Scale (NIHSS), is associated with change in thyroid function.

Results
Forty-five patients were evaluated in hyper-acute and acute stages, while 29 were followed through chronic stage. TSH levels decreased from hyper-acute (2.91 ± 0.65 μIU/mL) to acute (2.86 ± 0.46 μIU/mL) and chronic stages of stroke (1.93 ± 0.35 μIU/m, p = 0.95). fT3 levels decreased from hyper-acute (2.79 ± 0.09 pg/ml) to acute (2.37 ± 0.07 pg/ml) stages, but recovered in chronic stage (2.78 ± 0.10 pg/ml, p < 0.01). fT4 levels decreased from hyper-acute (1.64 ± 0.14 ng/dl) to acute (1.13 ± 0.03 ng/dl) stages, and increased in the chronic stage (1.16 ± 0.08 ng/dl, p = 0.02). One-unit increase in presenting NIHSS was associated with 0.04-unit decrease of fT3 from hyper-acute to the acute stage (p < 0.01).

Conclusion
There is a transient decrease of thyroid hormones after ischemic stroke, possibly driven by stroke severity. Larger studies are needed to validate these findings. Correction of thyroid function in acute stroke may be investigated to improve stroke outcomes.