bluuebunny/crossref_metadata_2025_split huggingface dataset:
“I do not know the advantages of having a general practitioner” - a qualitative study exploring the views of low-acuity emergency patients without a regular general practitioner toward primary care
Authors: Kümpel Lisa , Oslislo Sarah , Resendiz Cantu Rebecca , Möckel Martin , Heintze Christoph , Holzinger Felix 
Published: May 2024

Abstract
Background
Emergency departments (ED) worldwide have to cope with rising patient numbers. Low-acuity consulters who could receive a more suitable treatment in primary care (PC) increase caseloads, and lack of PC attachment has been discussed as a determinant. This qualitative study explores factors that contribute to non-utilization of general practitioner (GP) care among patients with no current attachment to a GP.

Method
Qualitative semi-structured telephone interviews were conducted with 32 low-acuity ED consulters with no self-reported attachment to a GP. Participants were recruited from three EDs in the city center of Berlin, Germany. Data were analyzed by qualitative content analysis.

Results
Interviewed patients reported heterogeneous factors contributing to their PC utilization behavior and underlying views and experiences. Participants most prominently voiced a rare need for medical services, a distinct mobility behavior, and a lack of knowledge about the role of a GP and health care options. Views about and experiences with GP care that contribute to non-utilization were predominantly related to little confidence in GP care, preference for directly consulting medical specialists, and negative experiences with GP care in the past. Contrasting their reported utilization behavior, many interviewees still recognized the advantages of GP care continuity.

Conclusion
Understanding reasons of low-acuity ED patients for GP non-utilization can play an important role in the design and implementation of patient-centered care interventions for PC integration. Increasing GP utilization, continuity of care and health literacy might have positive effects on patient decision-making in acute situations and in turn decrease ED burden.

Trial registration
German Clinical Trials Register: DRKS00023480; date: 2020/11/27.
Long COVID symptoms after 8-month recovery: persistent static lung hyperinflation associated with small airway dysfunction
Authors: Lo Po-Chun , Feng Jia-Yih , Hsiao Yi-Han , Su Kang-Cheng , Chou Kun-Ta , Chen Yuh-Min , Ko Hsin-Kuo , Perng Diahn-Warng 
Published: May 2024

Abstract
Background
Limited research has investigated the relationship between small airway dysfunction (SAD) and static lung hyperinflation (SLH) in patients with post-acute sequelae of COVID-19 (PASC) especially dyspnea and fatigue.

Methods
64 patients with PASC were enrolled between July 2020 and December 2022 in a prospective observational cohort. Pulmonary function tests, impulse oscillometry (IOS), and symptom questionnaires were performed two, five and eight months after acute infection. Multivariable logistic regression models were used to test the association between SLH and patient-reported outcomes.

Results
SLH prevalence was 53.1% (34/64), irrespective of COVID-19 severity. IOS parameters and circulating CD4/CD8 T-cell ratio were significantly correlated with residual volume to total lung capacity ratio (RV/TLC). Serum CD8 + T cell count was negatively correlated with forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) with statistical significance. Of the patients who had SLH at baseline, 57% continued to have persistent SLH after eight months of recovery, with these patients tending to be older and having dyspnea and fatigue. Post-COVID dyspnea was significantly associated with SLH and IOS parameters R5-R20, and AX with adjusted odds ratios 12.4, 12.8 and 7.6 respectively. SLH was also significantly associated with fatigue.

Conclusion
SAD and a decreased serum CD4/CD8 ratio were associated with SLH in patients with PASC. SLH may persist after recovery from infection in a substantial proportion of patients. SAD and dysregulated T-cell immune response correlated with SLH may contribute to the development of dyspnea and fatigue in patients with PASC.
The potential of Bacillus species isolated from Cinnamomum camphora for biofuel production
Authors: Hagaggi Noura Sh.A. , Rady Eman A. El 
Published: May 2024

Abstract
Background
Increasing concerns about climate change and global petroleum supply draw attention to the urgent need for the development of alternative methods to produce fuels. Consequently, the scientific community must devise novel ways to obtain fuels that are both sustainable and eco-friendly. Bacterial alkanes have numerous potential applications in the industry sector. One significant application is biofuel production, where bacterial alkanes can serve as a sustainable eco-friendly alternative to fossil fuels. This study represents the first report on the production of alkanes by endophytic bacteria.

Results
In this study, three Bacillus species, namely Bacillus atrophaeus Camph.1 (OR343176.1), Bacillus spizizenii Camph.2 (OR343177.1), and Bacillus aerophilus Camph.3 (OR343178.1), were isolated from the leaves of C. camphora. The isolates were then screened to determine their ability to produce alkanes in different culture media including nutrient broth (NB), Luria–Bertani (LB) broth, and tryptic soy broth (TSB). Depending on the bacterial isolate and the culture media used, different profiles of alkanes ranging from C8 to C31 were detected.

Conclusions
The endophytic B. atrophaeus Camph.1 (OR343176.1), B. spizizenii Camph.2 (OR343177.1), and B. aerophilus Camph.3 (OR343178.1), associated with C. camphora leaves, represent new eco-friendly approaches for biofuel production, aiming towards a sustainable future. Further research is needed to optimize the fermentation process and scale up alkane production by these bacterial isolates.
CRISPR-Cas13d screens identify KILR, a breast cancer risk-associated lncRNA that regulates DNA replication and repair
Authors: Wang Lu , Bitar Mainá , Lu Xue , Jacquelin Sebastien , Nair Sneha , Sivakumaran Haran , Hillman Kristine M. , Kaufmann Susanne , Ziegman Rebekah , Casciello Francesco , Gowda Harsha , Rosenbluh Joseph , Edwards Stacey L. , French Juliet D. 
Published: May 2024

Abstract
Background
Long noncoding RNAs (lncRNAs) have surpassed the number of protein-coding genes, yet the majority have no known function. We previously discovered 844 lncRNAs that were genetically linked to breast cancer through genome-wide association studies (GWAS). Here, we show that a subset of these lncRNAs alter breast cancer risk by modulating cell proliferation, and provide evidence that a reduced expression on one lncRNA increases breast cancer risk through aberrant DNA replication and repair.

Methods
We performed pooled CRISPR-Cas13d-based knockdown screens in breast cells to identify which of the 844 breast cancer-associated lncRNAs alter cell proliferation. We selected one of the lncRNAs that increased cell proliferation, KILR, for follow-up functional studies. KILR pull-down followed by mass spectrometry was used to identify binding proteins. Knockdown and overexpression studies were performed to assess the mechanism by which KILR regulates proliferation.

Results
We show that KILR functions as a tumor suppressor, safeguarding breast cells against uncontrolled proliferation. The half-life of KILR is significantly reduced by the risk haplotype, revealing an alternative mechanism by which variants alter cancer risk. Mechanistically, KILR sequesters RPA1, a subunit of the RPA complex required for DNA replication and repair. Reduced KILR expression promotes breast cancer cell proliferation by increasing the available pool of RPA1 and speed of DNA replication. Conversely, KILR overexpression promotes apoptosis in breast cancer cells, but not normal breast cells.

Conclusions
Our results confirm lncRNAs as mediators of breast cancer risk, emphasize the need to annotate noncoding transcripts in relevant cell types when investigating GWAS variants and provide a scalable platform for mapping phenotypes associated with lncRNAs.
An injectable refrigerated hydrogel for inducing local hypothermia and neuroprotection against traumatic brain injury in mice
Authors: Han Yuhan , Han Zhengzhong , Huang Xuyang , Li Shanshan , Jin Guoliang , Feng Junfeng , Wu Decheng , Liu Hongmei 
Published: May 2024

Abstract
Background
Hypothermia is a promising therapy for traumatic brain injury (TBI) in the clinic. However, the neuroprotective outcomes of hypothermia-treated TBI patients in clinical studies are inconsistent due to several severe side effects. Here, an injectable refrigerated hydrogel was designed to deliver 3-iodothyronamine (T1AM) to achieve a longer period of local hypothermia for TBI treatment. Hydrogel has four advantages: (1) It can be injected into injured sites after TBI, where it forms a hydrogel and avoids the side effects of whole-body cooling. (2) Hydrogels can biodegrade and be used for controlled drug release. (3) Released T1AM can induce hypothermia. (4) This hydrogel has increased medical value given its simple operation and ability to achieve timely treatment.

Methods
Pol/T hydrogels were prepared by a low-temperature mixing method and characterized. The effect of the Pol/T hydrogel on traumatic brain injury in mice was studied. The degradation of the hydrogel at the body level was observed with a small animal imager. Brain temperature and body temperature were measured by brain thermometer and body thermometer, respectively. The apoptosis of peripheral nerve cells was detected by immunohistochemical staining. The protective effect of the hydrogels on the blood–brain barrier (BBB) after TBI was evaluated by the Evans blue penetration test. The protective effect of hydrogel on brain edema after injury in mice was detected by Magnetic resonance (MR) in small animals. The enzyme linked immunosorbent assay (ELISA) method was used to measure the levels of inflammatory factors. The effects of behavioral tests on the learning ability and exercise ability of mice after injury were evaluated.

Results
This hydrogel was able to cool the brain to hypothermia for 12 h while maintaining body temperature within the normal range after TBI in mice. More importantly, hypothermia induced by this hydrogel leads to the maintenance of BBB integrity, the prevention of cell death, the reduction of the inflammatory response and brain edema, and the promotion of functional recovery after TBI in mice. This cooling method could be developed as a new approach for hypothermia treatment in TBI patients.

Conclusion
Our study showed that injectable and biodegradable frozen Pol/T hydrogels to induce local hypothermia in TBI mice can be used for the treatment of traumatic brain injury.

Graphical Abstract
Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort
Authors: Vanni I. , Pastorino L. , Andreotti V. , Comandini D. , Fornarini G. , Grassi M. , Puccini A. , Tanda E. T. , Pastorino A. , Martelli V. , Mastracci L. , Grillo F. , Cabiddu F. , Guadagno A. , Coco S. , Allavena E. , Barbero F. , Bruno W. , Dalmasso B. , Bellomo S. E. , Marchiò C. , Spagnolo F. , Sciallero S. , Berrino E. , Ghiorzo P. 
Published: May 2024

Abstract
Background
Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling.

Methods
Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification.

Results
The overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition.

Conclusions
Our study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.
PAX6/CXCL14 regulatory axis promotes the repair of corneal injury by enhancing corneal epithelial cell proliferation
Authors: Ma Ruijue , Li Yingxi , Dong Xiaoli , Zhang Yiming , Chen Xiaosu , Zhang Yue , Zou Haohan , Wang Yan 
Published: May 2024

Abstract
Background
Corneal injuries, often leading to severe vision loss or blindness, have traditionally been treated with the belief that limbal stem cells (LSCs) are essential for repair and homeostasis, while central corneal epithelial cells (CCECs) were thought incapable of such repair. However, our research reveals that CCECs can fully heal and maintain the homeostasis of injured corneas in rats, even without LSCs. We discovered that CXCL14, under PAX6’s influence, significantly boosts the stemness, proliferation, and migration of CCECs, facilitating corneal wound healing and homeostasis. This finding introduces CXCL14 as a promising new drug target for corneal injury treatment.

Methods
To investigate the PAX6/CXCL14 regulatory axis’s role in CCECs wound healing, we cultured human corneal epithelial cell lines with either increased or decreased expression of PAX6 and CXCL14 using adenovirus transfection in vitro. Techniques such as coimmunoprecipitation, chromatin immunoprecipitation, immunofluorescence staining, western blot, real-time PCR, cell colony formation, and cell cycle analysis were employed to validate the axis’s function. In vivo, a rat corneal epithelial injury model was developed to further confirm the PAX6/CXCL14 axis’s mechanism in repairing corneal damage and maintaining corneal homeostasis, as well as to assess the potential of CXCL14 protein as a therapeutic agent for corneal injuries.

Results
Our study reveals that CCECs naturally express high levels of CXCL14, which is significantly upregulated by PAX6 following corneal damage. We identified SDC1 as CXCL14’s receptor, whose engagement activates the NF-κB pathway to stimulate corneal repair by enhancing the stemness, proliferative, and migratory capacities of CCECs. Moreover, our research underscores CXCL14’s therapeutic promise for corneal injuries, showing that recombinant CXCL14 effectively accelerates corneal healing in rat models.

Conclusion
CCECs play a critical and independent role in the repair of corneal injuries and the maintenance of corneal homeostasis, distinct from that of LSCs. The PAX6/CXCL14 regulatory axis is pivotal in this process. Additionally, our research demonstrates that the important function of CXCL14 in corneal repair endows it with the potential to be developed into a novel therapeutic agent for treating corneal injuries.
Efficacy of hypertonic dextrose proliferation therapy in the treatment of rotator cuff lesions: a meta-analysis
Authors: Zhang Ting , Wang YanFu , Ding Lin , Ma ChaoYang 
Published: May 2024

Abstract
Background
One of the most prevalent illnesses of the shoulder is rotator cuff tendinosis, which is also a major contributor to shoulder discomfort and shoulder joint dysfunction. According to statistics, rotator cuff tendinosis occurs in 0.3–5.5% of cases and affects 0.5–7.4% of people annually. It will be necessary to conduct a meta-analysis to evaluate the efficacy of hypertonic glucose proliferation therapy in the treatment of rotator cuff problems.

Methods
The databases Cochrane PubMed, Library, Web of Science and EMbase, are retrieved by the computer. Individuals with rotator cuff lesions in the intervention group were treated with hypertonic dextrose proliferation therapy, whereas individuals in the control condition were treated with a placebo. Outcome markers for rotator cuff lesions patients; Pursuant to studies, the visual analogue scale (VAS) score, the shoulder pain & disability index (SPADI), & other metrics are used to evaluate the effects of hypertonic dextrose proliferation treatment on individuals with rotator cuff diseases. After carefully evaluating the calibre of the literature, data analysis was performed utilising the RevMan 5.3 programme.

Results
Meta-analysis finally contained 6 papers. In six investigations, the test & control group’s VAS scores improved, with the test team’s score considerably outperforming the control team [standardized mean difference (SMD): 1.10; 95% Cl: 0.37,1.83; P < 0.01], shoulder pain and disability index (SPADI) score (SMD:8.13; 95% Cl: 5.34,10.91; P < 0.01), Flexion (SMD:5.73; 95% Cl: 0.99,10.47; P < 0.05), Abduction (SMD:6.49; 95% Cl: 0.66,12.31; P < 0.05), Internal rotation (SMD:-1.74; 95% Cl: -4.25,0.78; P = 0.176) and External rotation (SMD:2.78; 95% Cl: -0.13,5.69; P = 0.062).

Conclusion
The findings of this study suggest that individuals with rotator cuff injuries may benefit from hypertonic dextrose proliferation treatment based on the visual analogue scale (VAS) score, the Shoulder Pain and Disability Index (SPADI) score, Flexion, & Abduction. These results must, nevertheless, be supported by high-caliber follow-up research.
Genetic organization of an M protein trans-acting positive regulator (Mga) orthologue and its adjacent M-like protein (SCM) alleles in Streptococcus canis
Authors: Takahashi Takashi , Maeda Takahiro , Yoshida Haruno , Goto Mieko , Tsuyuki Yuzo , Kim Jae-Seok 
Published: May 2024

Abstract
Objective
The purpose of this study was to identify the M protein trans-acting positive regulator (Mga) orthologue and its adjacent M-like protein (SCM) alleles in Streptococcus canis.

Results
Using the 39 SCM allele isolates and polymerase chain reaction-based amplification and sequencing, we obtained the deduced Mga amino acid (AA) sequences. The 22 Mga sequences in whole-genome sequences were obtained by searching the National Collection of Type Cultures 12,191(T) Mga sequence into the database. The percentage identity to the type-strain Mga sequence was examined along with its size. The presence of the Mga-specific motifs was confirmed. Of the 62 strains, we identified 59 Mga sequences with an AA size of 509 (except for four different sizes). Percentage identity ranged from 96.66 to 100% with the confirmed Mga-specific motifs and diverse SCM allele populations. Our findings support the presence of an Mga orthologue and diverse SCM allele populations.
Machine learning unveils an immune-related DNA methylation profile in germline DNA from breast cancer patients
Authors: Lee Ning Yuan , Hum Melissa , Tan Guek Peng , Seah Ai Choo , Ong Pei-Yi , Kin Patricia T. , Lim Chia Wei , Samol Jens , Tan Ngiap Chuan , Law Hai-Yang , Tan Min-Han , Lee Soo-Chin , Ang Peter , Lee Ann S. G. 
Published: May 2024

Abstract
Background
There is an unmet need for precise biomarkers for early non-invasive breast cancer detection. Here, we aimed to identify blood-based DNA methylation biomarkers that are associated with breast cancer.

Methods
DNA methylation profiling was performed for 524 Asian Chinese individuals, comprising 256 breast cancer patients and 268 age-matched healthy controls, using the Infinium MethylationEPIC array. Feature selection was applied to 649,688 CpG sites in the training set. Predictive models were built by training three machine learning models, with performance evaluated on an independent test set. Enrichment analysis to identify transcription factors binding to regions associated with the selected CpG sites and pathway analysis for genes located nearby were conducted.

Results
A methylation profile comprising 51 CpGs was identified that effectively distinguishes breast cancer patients from healthy controls achieving an AUC of 0.823 on an independent test set. Notably, it outperformed all four previously reported breast cancer-associated methylation profiles. Enrichment analysis revealed enrichment of genomic loci associated with the binding of immune modulating AP-1 transcription factors, while pathway analysis of nearby genes showed an overrepresentation of immune-related pathways.

Conclusion
This study has identified a breast cancer-associated methylation profile that is immune-related to potential for early cancer detection.
Cholecystokinin B receptor agonists alleviates anterograde amnesia in cholecystokinin-deficient and aged Alzheimer's disease mice
Authors: Zhang Nan , Sui Yixuan , Jendrichovsky Peter , Feng Hemin , Shi Heng , Zhang Xu , Xu Shenghui , Sun Wenjian , Zhang Huatang , Chen Xi , Tortorella Micky D. , He Jufang 
Published: May 2024

Abstract
Background
As one major symptom of Alzheimer’s disease (AD), anterograde amnesia describes patients with an inability in new memory formation. The crucial role of the entorhinal cortex in forming new memories has been well established, and the neuropeptide cholecystokinin (CCK) is reported to be released from the entorhinal cortex to enable neocortical associated memory and long-term potentiation. Though several studies reveal that the entorhinal cortex and CCK are related to AD, it is less well studied. It is unclear whether CCK is a good biomarker or further a great drug candidate for AD.

Methods
mRNA expressions of CCK and CCK-B receptor (CCKBR) were examined in two mouse models, 3xTg AD and CCK knock-out (CCK−/−) mice. Animals’ cognition was investigated with Morris water maze, novel object recognition test and neuroplasticity with in-vitro electrophysiological recording. Drugs were given intraperitoneally to animals to investigate the rescue effects on cognitive deficits, or applied to brain slices directly to explore the influence in inducement of long-term potentiation.

Results
Aged 3xTg AD mice exhibited reduced CCK mRNA expression in the entorhinal cortex but reduced CCKBR expression in the neocortex and hippocampus, and impaired cognition and neuroplasticity comparable with CCK−/− mice. Importantly, the animals displayed improved performance and enhanced long-term potentiation after the treatment of CCKBR agonists.

Conclusions
Here we provide more evidence to support the role of CCK in learning and memory and its potential to treat AD. We elaborated on the rescue effect of a promising novel drug, HT-267, on aged 3xTg AD mice. Although the physiological etiology of CCK in AD still needs to be further investigated, this study sheds light on a potential pharmaceutical candidate for AD and dementia.